Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention versus usual care on cardiovascular disease (CRHCP): an open-label, blinded-endpoint, cluster-randomised trial.

Abstract:
BACKGROUND
Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention on cardiovascular disease has not been established. We aimed to test the effectiveness of such an intervention compared with usual care on risk of cardiovascular disease and all-cause death among individuals with hypertension.

METHODS
In this open-label, blinded-endpoint, cluster-randomised trial, we recruited individuals aged at least 40 years with an untreated systolic blood pressure of at least 140 mm Hg or a diastolic blood pressure of at least 90 mm Hg (≥130 mm Hg and ≥80 mm Hg for those at high risk for cardiovascular disease or if currently taking antihypertensive medication). We randomly assigned (1:1) 326 villages to a non-physician community health-care provider-led intervention or usual care, stratified by provinces, counties, and townships. In the intervention group, trained non-physician community health-care providers initiated and titrated antihypertensive medications according to a simple stepped-care protocol to achieve a systolic blood pressure goal of less than 130 mm Hg and diastolic blood pressure goal of less than 80 mm Hg with supervision from primary care physicians. They also delivered discounted or free antihypertensive medications and health coaching for patients. The primary effectiveness outcome was a composite outcome of myocardial infarction, stroke, heart failure requiring hospitalisation, and cardiovascular disease death during the 36-month follow-up in the study participants. Safety was assessed every 6 months. This trial is registered with ClinicalTrials.gov, NCT03527719.

FINDINGS
Between May 8 and Nov 28, 2018, we enrolled 163 villages per group with 33 995 participants. Over 36 months, the net group difference in systolic blood pressure reduction was -23·1 mm Hg (95% CI -24·4 to -21·9; p<0·0001) and in diastolic blood pressure reduction, it was -9·9 mm Hg (-10·6 to -9·3; p<0·0001). Fewer patients in the intervention group than the usual care group had a primary outcome (1·62% vs 2·40% per year; hazard ratio [HR] 0·67, 95% CI 0·61-0·73; p<0·0001). Secondary outcomes were also reduced in the intervention group: myocardial infarction (HR 0·77, 95% CI 0·60-0·98; p=0·037), stroke (0·66, 0·60-0·73; p<0·0001), heart failure (0·58, 0·42-0·81; p=0·0016), cardiovascular disease death (0·70, 0·58-0·83; p<0·0001), and all-cause death (0·85, 0·76-0·95; p=0·0037). The risk reduction of the primary outcome was consistent across subgroups of age, sex, education, antihypertensive medication use, and baseline cardiovascular disease risk. Hypotension was higher in the intervention than in the usual care group (1·75% vs 0·89%; p<0·0001).

INTERPRETATION
The non-physician community health-care provider-led intensive blood pressure intervention is effective in reducing cardiovascular disease and death.

FUNDING
The Ministry of Science and Technology of China and the Science and Technology Program of Liaoning Province, China.


Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): a randomised controlled trial.

Abstract:
BACKGROUND
Mediterranean and low-fat diets are effective in the primary prevention of cardiovascular disease. We did a long-term randomised trial to compare the effects of these two diets in secondary prevention of cardiovascular disease.

METHODS
The CORDIOPREV study was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive a Mediterranean diet or a low-fat diet intervention, with a follow-up of 7 years. Clinical investigators (physicians, investigators, and clinical endpoint committee members) were masked to treatment assignment; participants were not. A team of dietitians did the dietary interventions. The primary outcome (assessed by intention to treat) was a composite of major cardiovascular events, including myocardial infarction, revascularisation, ischaemic stroke, peripheral artery disease, and cardiovascular death. This study is registered with ClinicalTrials.gov, NCT00924937.

FINDINGS
From Oct 1, 2009, to Feb 28, 2012, a total of 1002 patients were enrolled, 500 (49·9%) in the low-fat diet group and 502 (50·1%) in the Mediterranean diet group. The mean age was 59·5 years (SD 8·7) and 827 (82·5%) of 1002 patients were men. The primary endpoint occurred in 198 participants: 87 in the Mediterranean diet group and 111 in the low-fat group (crude rate per 1000 person-years: 28·1 [95% CI 27·9-28·3] in the Mediterranean diet group vs 37·7 [37·5-37·9] in the low-fat group, log-rank p=0·039). Multivariable-adjusted hazard ratios (HRs) of the different models ranged from 0·719 (95% CI 0·541-0·957) to 0·753 (0·568-0·998) in favour of the Mediterranean diet. These effects were more evident in men, with primary endpoints occurring in 67 (16·2%) of 414 men in the Mediterranean diet group versus 94 (22·8%) of 413 men in the low-fat diet group (multiadjusted HR 0·669 [95% CI 0·489-0·915], log-rank p=0·013), than in 175 women for whom no difference was found between groups.

INTERPRETATION
In secondary prevention, the Mediterranean diet was superior to the low-fat diet in preventing major cardiovascular events. Our results are relevant to clinical practice, supporting the use of the Mediterranean diet in secondary prevention.

FUNDING
Fundacion Patrimonio Comunal Olivarero; Fundacion Centro para la Excelencia en Investigacion sobre Aceite de Oliva y Salud; local, regional, and national Spanish Governments; European Union.


Performance of cardiovascular disease risk prediction equations in more than 14 000 survivors of cancer in New Zealand primary care: a validation study.

Abstract:
BACKGROUND
People with cancer have an increased risk of cardiovascular disease. Risk prediction equations developed in New Zealand accurately predict 5-year cardiovascular disease risk in a general primary care population in the country. We assessed the performance of these equations for survivors of cancer in New Zealand.

METHODS
For this validation study, patients aged 30-74 years from the PREDICT open cohort study, which was used to develop the New Zealand cardiovascular disease risk prediction equations, were included in the analysis if they had a primary diagnosis of invasive cancer at least 2 years before the date of the first cardiovascular disease risk assessment. The risk prediction equations are sex-specific and include the following predictors: age, ethnicity, socioeconomic deprivation index, family history of cardiovascular disease, smoking status, history of atrial fibrillation and diabetes, systolic blood pressure, total cholesterol to HDL cholesterol ratio, and preventive pharmacotherapy (blood-pressure-lowering, lipid-lowering, and antithrombotic drugs). Calibration was assessed by comparing the mean predicted 5-year cardiovascular disease risk, estimated using the risk prediction equations, with the observed risk across deciles of risk, for men and women, and according to the three clinical 5-year cardiovascular disease risk groups in New Zealand guidelines (<5%, 5% to <15%, and ≥15%). Discrimination was assessed by Harrell's C statistic.

FINDINGS
14 263 patients were included in the study. The mean age was 61 years (SD 9) for men and 60 years (SD 8) for women, with a median follow-up of 5·8 years for men and 5·7 years for women. The observed cardiovascular disease risk was underpredicted by a maximum of 2·5% in male and 3·2% in female decile groups. When patients were grouped according to clinical risk groups, observed cardiovascular disease risk was underpredicted by less than 2% in the lower risk groups and overpredicted by 2·2% for men and 3·3% for women in the highest risk group. Harrell's C statistics were 0·67 (SE 0·01) for men and 0·73 (0·01) for women.

INTERPRETATION
The New Zealand cardiovascular disease risk prediction equations reasonably predicted the observed 5-year cardiovascular disease risk in survivors of cancer in the country, in whom risk prediction was considered clinically appropriate. Prediction could be improved by adding cancer-specific variables and considering competing risks. Our findings suggest that the equations are reasonable clinical tools for use in survivors of cancer in New Zealand.

FUNDING
Auckland Medical Research Foundation, Health Research Council of New Zealand.


Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis

Abstract: Summary Background The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure. Methods We did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from <120 to ≥170 mm Hg). The primary outcome was a major cardiovascular event (defined as a composite of fatal and non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring admission to hospital), analysed as per intention to treat. Findings Data for 344 716 participants from 48 randomised clinical trials were available for this analysis. Pre-randomisation mean systolic/diastolic blood pressures were 146/84 mm Hg in participants with previous cardiovascular disease (n=157 728) and 157/89 mm Hg in participants without previous cardiovascular disease (n=186 988). There was substantial spread in participants' blood pressure at baseline, with 31 239 (19·8%) of participants with previous cardiovascular disease and 14 928 (8·0%) of individuals without previous cardiovascular disease having a systolic blood pressure of less than 130 mm Hg. The relative effects of blood pressure-lowering treatment were proportional to the intensity of systolic blood pressure reduction. After a median 4·15 years' follow-up (Q1–Q3 2·97–4·96), 42 324 participants (12·3%) had at least one major cardiovascular event. In participants without previous cardiovascular disease at baseline, the incidence rate for developing a major cardiovascular event per 1000 person-years was 31·9 (95% CI 31·3–32·5) in the comparator group and 25·9 (25·4–26·4) in the intervention group. In participants with previous cardiovascular disease at baseline, the corresponding rates were 39·7 (95% CI 39·0–40·5) and 36·0 (95% CI 35·3–36·7), in the comparator and intervention groups, respectively. Hazard ratios (HR) associated with a reduction of systolic blood pressure by 5 mm Hg for a major cardiovascular event were 0·91, 95% CI 0·89–0·94 for partipants without previous cardiovascular disease and 0·89, 0·86–0·92, for those with previous cardiovascular disease. In stratified analyses, there was no reliable evidence of heterogeneity of treatment effects on major cardiovascular events by baseline cardiovascular disease status or systolic blood pressure categories. Interpretation In this large-scale analysis of randomised trials, a 5 mm Hg reduction of systolic blood pressure reduced the risk of major cardiovascular events by about 10%, irrespective of previous diagnoses of cardiovascular disease, and even at normal or high–normal blood pressure values. These findings suggest that a fixed degree of pharmacological blood pressure lowering is similarly effective for primary and secondary prevention of major cardiovascular disease, even at blood pressure levels currently not considered for treatment. Physicians communicating the indication for blood pressure lowering treatment to their patients should emphasise its importance on reducing cardiovascular risk rather than focusing on blood pressure reduction itself. Funding British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.

Amanda Larry Ale Folkert W Nigel S Eivind Henry Frank P J Adler Agodoa Algra Asselbergs Beckett Berge Black


Triple cardiovascular disease detection with an artificial intelligence-enabled stethoscope (TRICORDER) in the UK: a cluster-randomised controlled implementation trial.

Abstract:
BACKGROUND
Early detection of cardiovascular disease is a global public health priority. Artificial intelligence (AI)-enabled stethoscopes offer robust performance characteristics in point-of-care detection of heart failure, atrial fibrillation, and valvular heart disease (VHD). We conducted a pragmatic, cluster-randomised controlled implementation trial to determine the real-world effect and implementation challenges of AI-stethoscopes.

METHODS
UK primary care practices were cluster randomised 1:1 to intervention (training and implementation in use of AI-stethoscopes in routine care) or control (routine care). Given the nature of the intervention, masking of participants (practices, clinicians, and patients) was not feasible. During cardiac examinations, the AI stethoscope recorded 15 s of single-lead electrocardiogram and phonocardiogram signals for input to three AI algorithms that returned binary predictions for the presence or absence of reduced left ventricular ejection fraction (≤40%), atrial fibrillation, and VHD (all with regulatory approval). The primary endpoint was incidence of any newly coded diagnosis of heart failure (all subtypes), expressed per 1000 patient-years (incidence rate ratio [IRR]), derived from a UK National Health Service Secure Data Environment. A coprimary endpoint stratified detection of heart failure by place of diagnosis (community-based vs via hospital admission). Secondary endpoints included atrial fibrillation and VHD detection rates, performance characteristics of the AI-stethoscope, use rates, and clinician-reported implementation barriers and enablers.

FINDINGS
Between Oct 30, 2023, and May 22, 2024, 205 practices were randomly assigned (96 to the intervention arm [701 933 registered patients] and 109 to the control arm [851 242 registered patients]). Intervention practices recorded 12 725 patient examinations with the AI-stethoscope, across 972 clinical users. Intention-to-treat analysis found heart failure detection did not differ between groups (IRR 0·94 [95% CI 0·86-1·02]); with no difference in community-based or hospital-based diagnoses (p>0·05).

INTERPRETATION
Implementation of an AI stethoscope in routine primary care did not significantly increase detection of heart failure or increase community-based diagnosis after 12 months of implementation. AI stethoscope use was independently associated with significantly higher detection rates of heart failure, as well as atrial fibrillation and VHD. This randomised controlled implementation trial establishes a pragmatic design with randomisation that generates real-world data essential for understanding and overcoming the barriers to implementation of innovation in health care.

FUNDING
National Institute for Health and Care Research, British Heart Foundation, and Imperial Health Charity.


Pharmacological blood-pressure lowering for the prevention of cardiovascular disease and death across the full spectrum of chronic kidney disease severity: an individual-participant data meta-analysis.

Abstract:
BACKGROUND
Individuals with chronic kidney disease (CKD), particularly those at more advanced stages, have been systematically under-represented in randomised controlled trials (RCTs) of blood-pressure-lowering treatment due to safety concerns, leading to a persistent paucity of evidence for cardiovascular risk management in this high-risk group. We investigated the effect of blood-pressure-lowering treatment on the risk of major cardiovascular disease and death across the full spectrum of CKD stages and by key clinical subgroups.

METHODS
We conducted a one-stage meta-analysis of individual-participant data from RCTs in which participants were randomly assigned to a blood-pressure-lowering therapy versus a comparator. We used RCTs collated in the Blood Pressure Lowering Treatment Trialists' Collaboration dataset, published at any time in any language, which were eligible for inclusion if they had at least 1000 person-years of follow-up per arm, baseline blood-pressure and creatinine measurements, and time-to-event outcomes; those with unclear randomisation procedures or restricted to heart failure or acute care settings were excluded. Participants with a documented history of heart failure or extreme creatinine values were excluded. No age criteria were applied. The primary outcome was major cardiovascular events, defined as a composite of fatal or non-fatal stroke, ischaemic heart disease, or hospitalisation for, or death from, heart failure. Relative treatment effects were estimated with a stratified Cox proportional hazards model. Heterogeneity of treatment effects was evaluated across prespecified subgroups defined by CKD status, CKD stage (1-5), diabetes, proteinuria, and baseline blood pressure. A stratified network meta-analysis was performed to examine whether treatment effects differed by defined subgroups within each of five principal antihypertensive drug classes. The systematic review was registered in PROSPERO (CRD42018099283).

FINDINGS
From 52 RCTs (363 684 participants), a total of 285 124 participants from 46 randomised trials met the eligibility criteria; 116 145 (40·7%) were women, 168 979 (59·3%) were men, 59 185 (20·7%) had CKD at baseline, and 86 067 (30·2%) had type 2 diabetes. During a median follow-up of 4·4 years (IQR 3·2-5·1), a 5 mm Hg reduction in systolic blood pressure reduced the risk of major cardiovascular disease in individuals with CKD (hazard ratio [HR] 0·91 [95% CI 0·87-0·94]) and without CKD (0·90 [0·88-0·93]; pinteraction>0·99). Furthermore, these observed relative risk reductions were consistent across all CKD stages, including severe stages 4-5 (pinteraction>0·99). Similar treatment effects were observed by proteinuria status and across blood-pressure categories, down to <120/70 mm Hg. However, the relative treatment effect in individuals with CKD was notably attenuated among those with coexisting diabetes (HR 0·96 [95% CI 0·90-1·02]) compared with those without (0·88 [0·84-0·93]; pinteraction=0·044). The stratified analysis within each drug class showed that the class-specific effects of antihypertensive agents versus placebo on cardiovascular disease risk remained unchanged across the investigated subgroups.

INTERPRETATION
In the context of cardiovascular risk reduction, the relative benefit of blood-pressure lowering in patients with CKD is similar to that in individuals without CKD, with consistent efficacy across all CKD stages, blood-pressure thresholds, and proteinuria status. However, notably, this relative benefit is attenuated in patients with CKD and concomitant diabetes, underscoring the requirement for adapted therapeutic strategies in this high-risk subgroup. Moreover, the class-specific effects of principal antihypertensives in CKD mirror those observed in the broader population, independent of CKD stage or proteinuria status.

FUNDING
British Heart Foundation.


Factors affecting the delivery of community-based salon interventions to prevent cardiovascular disease and breast cancer among ethnically diverse women in South London: a concept-mapping approach.

Abstract:
BACKGROUND
In the UK, women from ethnically diverse and socioeconomically deprived communities are at increased risk of underdiagnosis of cardiovascular disease (CVD) and breast cancer. Promoting CVD prevention and awareness of breast cancer screening via community salons and primary health care partnerships can improve uptake of screening services and early detection.

METHODS
Concept mapping is a multistage mixed methods participatory approach comprised of six stages: preparation, brainstorming, structuring of statements, representing statements, interpretation and utilisation of maps using Group wisdom software. A target of 20 salons, excluding male-only salons were approached. Salons included Salons included hairdressing or hairdressing and beauty salons. Purposeful and convenience sampling (online and face to face) among UK salons (hair and beauty) was conducted. Participants were given a focus prompt "What would be some factors that can influence the ability of salons to deliver this service?" and required to generate statements, which were sorted into categories based on similarity and rated for importance and feasibility. Concept maps using multidimensional scaling and hierarchical cluster analyses were produced.

FINDINGS
Of 35 participants invited, 25 (71%) consented and agreed to take part in concept mapping. Reported ages were 26-35 years (n=5, 20%), 36-45 years (n=12, 48%), 46-55 years (n=3, 12%), 56-65 years (n=5, 20%), and no age reported (n=10, 40%). Around 36% (n=9) of participants were from non-White ethnic groups, with 12% (n=3) being male and 88% (n=22) female. Seven clusters emerged. Salon staff capabilities and capacities and engaging in health conversations in community salons scored average bridging values of 0·09 and 0·2 respectively, indicating good cluster homogeneity (similar meaning statements were closely sorted). Facilitating health-care access with GP practices was rated highly important to effectively promote the intervention. Engaging in health conversations in community salons and salon incentives for participation were examples of factors that were highly feasible to address. The r correlation coefficient was 0·68 between importance and feasibility to address factors affecting community health interventions.

INTERPRETATION
Salons are well positioned to support health promotion interventions. Actionable priorities were identified for a salon-GP surgery partnership to promote CVD prevention through lifestyle changes and health check uptake, raising breast cancer screening awareness and address issue of equity.

FUNDING
National Institute of Health and Care Research (NIHR), Research for Patient Benefit (RfPB) Programme NIHR202769.


Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial.

Abstract:
BACKGROUND
Drug combinations rather than increasing doses of one drug can achieve greater efficacy and lower risks. Thus, as an alternative to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy can lower LDL cholesterol concentrations effectively while reducing adverse effects. However, evidence from randomised trials to compare long-term clinical outcomes is needed.

METHODS
In this randomised, open-label, non-inferiority trial, patients with atherosclerotic cardiovascular disease (ASCVD) at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke, in the intention-to-treat population with a non-inferiority margin of 2·0%. This trial is registered with ClinicalTrials.gov, NCT03044665 and is complete.

FINDINGS
Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled: 1894 patients to the combination therapy group and 1886 to the high-intensity statin monotherapy group. The primary endpoint occurred in 172 patients (9·1%) in the combination therapy group and 186 patients (9·9%) in the high-intensity statin monotherapy group (absolute difference -0·78%; 90% CI -2·39 to 0·83). LDL cholesterol concentrations of less than 70 mg/dL at 1, 2, and 3 years were observed in 73%, 75%, and 72% of patients in the combination therapy group, and 55%, 60%, and 58% of patients in the high-intensity statin monotherapy group (all p<0·0001). Discontinuation or dose reduction of the study drug by intolerance was observed in 88 patients (4·8%) and 150 patients (8·2%), respectively (p<0·0001).

INTERPRETATION
Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction.

FUNDING
Hanmi Pharmaceutical.


Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study.

Abstract:
BACKGROUND
There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries.

METHODS
In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants' metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35-70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586.

FINDINGS
In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5-12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9-5·2] per 1000 person-years) and 4911 in men (8·2 [8·0-8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01-1·21) in women and 1·28 (1·19-1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98-1·21) in women and 1·42 (1·25-1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08-1·26]) than in men (1·07 [0·99-1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5-2·1] in women vs 10·7% [8·8-12·6] in men).

INTERPRETATION
Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women.

FUNDING
Funding sources are listed at the end of the Article.


Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: an individual participant data meta-analysis.

Abstract:
BACKGROUND
In randomised controlled trials, fixed-dose combination treatments (or polypills) have been shown to reduce a composite of cardiovascular disease outcomes in primary prevention. However, whether or not aspirin should be included, effects on specific outcomes, and effects in key subgroups are unknown.

METHODS
We did an individual participant data meta-analysis of large randomised controlled trials (each with ≥1000 participants and ≥2 years of follow-up) of a fixed-dose combination treatment strategy versus control in a primary cardiovascular disease prevention population. We included trials that evaluated a fixed-dose combination strategy of at least two blood pressure lowering agents plus a statin (with or without aspirin), compared with a control strategy (either placebo or usual care). The primary outcome was time to first occurrence of a composite of cardiovascular death, myocardial infarction, stroke, or arterial revascularisation. Additional outcomes included individual cardiovascular outcomes and death from any cause. Outcomes were also evaluated in groups stratified by the inclusion of aspirin in the fixed-dose treatment strategy, and effect sizes were estimated in prespecified subgroups based on risk factors. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to compare strategies.

FINDINGS
Three large randomised trials were included in the analysis (TIPS-3, HOPE-3, and PolyIran), with a total of 18 162 participants. Mean age was 63·0 years (SD 7·1), and 9038 (49·8%) participants were female. Estimated 10-year cardiovascular disease risk for the population was 17·7% (8·7). During a median follow-up of 5 years, the primary outcome occurred in 276 (3·0%) participants in the fixed-dose combination strategy group compared with 445 (4·9%) in the control group (hazard ratio 0·62, 95% CI 0·53-0·73, p<0·0001). Reductions were also observed for the separate components of the primary outcome: myocardial infarction (0·52, 0·38-0·70), revascularisation (0·54, 0·36-0·80), stroke (0·59, 0·45-0·78), and cardiovascular death (0·65, 0·52-0·81). Significant reductions in the primary outcome and its components were observed in the analyses of fixed-dose combination strategies with and without aspirin, with greater reductions for strategies including aspirin. Treatment effects were similar at different lipid and blood pressure levels, and in the presence or absence of diabetes, smoking, or obesity. Gastrointestinal bleeding was uncommon but slightly more frequent in the fixed-dose combination strategy with aspirin group versus control (19 [0·4%] vs 11 [0·2%], p=0·15). The frequencies of haemorrhagic stroke (10 [0·2%] vs 15 [0·3%]), fatal bleeding (two [<0·1%] vs four [0·1%]), and peptic ulcer disease (32 [0·7%] vs 34 [0·8%]) were low and did not differ significantly between groups. Dizziness was more common with fixed-dose combination treatment (1060 [11·7%] vs 834 [9·2%], p<0·0001).

INTERPRETATION
Fixed-dose combination treatment strategies substantially reduce cardiovascular disease, myocardial infarction, stroke, revascularisation, and cardiovascular death in primary cardiovascular disease prevention. These benefits are consistent irrespective of cardiometabolic risk factors.

FUNDING
Population Health Research Institute.


Modifiable risk factors, cardiovascular disease and mortality in 155,722 individuals from 21 high-, middle-, and low-income countries

Abstract: Background: Global estimates of the impact of common modifiable risk factors on cardiovascular disease (CVD) and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methodology to prospectively evaluate the impact of modifiable risk factors on CVD and mortality across 21 countries (spanning five continents) at different economic levels. Methods: In a multi-national, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and major CVD in 155,722 community-dwelling participants (ages 35–70 years at enrollment) from 21 high-, middle-, or low-income countries (HIC, MIC or LIC) followed for a median of 9·5 years. We describe the prevalence, hazard ratios, and population attributable fractions (PAFs) for CVD and mortality associated with a cluster of behavioural factors (i.e. tobacco, alcohol, diet, physical activity and sodium intake), metabolic factors (i.e. lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (i.e. education, symptoms of depression), strength, household (solid fuel for cooking) and ambient PM 2·5 air pollution. Findings: Mean age of the population was 50·2 years of age, 58·3% were female, 52·6% were from urban areas, 11·1% from HIC, 65·9% from MIC, and 23·0% from LIC. Over 70% of CVD cases and deaths in the overall cohort were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for CVD (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12.5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for CVD (although different statistical methods were used for this analysis). In MIC and LIC, the importance of household air pollution, poor diet, low education, and low grip strength were larger compared with HIC. Interpretation: The majority of CVD cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global impacts (e.g. hypertension, education), others (e.g. household air pollution, poor diet) vary by a country’s economic level. Health policies should focus on risk factors that have the greatest effects on averting CVD and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries.


Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis.


Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis

Abstract: Summary Background The effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline. Methods We did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded. Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (<55 years, 55–64 years, 65–74 years, 75–84 years, and ≥85 years) and blood pressure categories (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg systolic blood pressure and from <70 mm Hg to ≥110 mm Hg diastolic). We used a fixed effects one-stage approach and applied Cox proportional hazard models, stratified by trial, to analyse the data. The primary outcome was defined as either a composite of fatal or non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring hospital admission. Findings We included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and 4788 (1·3%) 85 years and older. The hazard ratios for the risk of major cardiovascular events per 5 mm Hg reduction in systolic blood pressure for each age group were 0·82 (95% CI 0·76–0·88) in individuals younger than 55 years, 0·91 (0·88–0·95) in those aged 55–64 years, 0·91 (0·88–0·95) in those aged 65–74 years, 0·91 (0·87–0·96) in those aged 75–84 years, and 0·99 (0·87–1·12) in those aged 85 years and older (adjusted pinteraction=0·050). Similar patterns of proportional risk reductions were observed for a 3 mm Hg reduction in diastolic blood pressure. Absolute risk reductions for major cardiovascular events varied by age and were larger in older groups (adjusted pinteraction=0·024). We did not find evidence for any clinically meaningful heterogeneity of relative treatment effects across different baseline blood pressure categories in any age group. Interpretation Pharmacological blood pressure reduction is effective into old age, with no evidence that relative risk reductions for prevention of major cardiovascular events vary by systolic or diastolic blood pressure levels at randomisation, down to less than 120/70 mm Hg. Pharmacological blood pressure reduction should, therefore, be considered an important treatment option regardless of age, with the removal of age-related blood-pressure thresholds from international guidelines. Funding British Heart Foundation, National Institute of Health Research Oxford Biomedical Research Centre, Oxford Martin School.

Kazem Zeinab Milad Emma Dexter Malgorzata Jeannette Rich Rahimi Bidel Nazarzadeh Copland Canoy Wamil Majert


Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial.


Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial.

Abstract:
BACKGROUND
The SELECT trial found semaglutide reduced major adverse cardiovascular events (MACE) in patients with overweight or obesity with cardiovascular disease but without diabetes. We report a prespecified analysis of the SELECT trial on the relationships between baseline adiposity measures, treatment-induced adiposity changes, and subsequent MACE risk.

METHODS
Patients aged at least 45 years, with a BMI of at least 27 kg/m2 were enrolled in 41 countries (804 sites) and randomised 1:1 to once-weekly semaglutide 2·4 mg or placebo. The primary outcome was time to first MACE (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Adiposity measures included weight and waist circumference. In this analysis, risk of MACE occurring after 20 weeks was assessed between patients by adiposity changes in the first 20 weeks and, in a separate analysis, all in-trial MACE were assessed between patients by adiposity changes over 104 weeks. This trial is registered with ClinicalTrials.gov, NCT03574597.

FINDINGS
Semaglutide significantly reduced MACE incidence compared with placebo among 17 604 patients enrolled in SELECT, with consistent benefits across all baseline weight and waist circumference categories. In the semaglutide group, analyses for linear trends showed lower baseline bodyweight and waist circumference were associated with lower incidence of MACE-an average 4% reduction in risk per 5 kg lower bodyweight (hazard ratio [HR] 0·96 [95% CI 0·94-0·99]; p=0·001) and per 5 cm smaller waist circumference (0·96 [0·93-0·99]; p=0·004). In the placebo group, lower baseline waist circumference (0·96 [0·94-0·99]; p=0·007), but not bodyweight (0·99 [0·97-1·01]; p=0·28), was associated with a lower MACE risk and weight loss was paradoxically associated with increased MACE risk. In those receiving semaglutide there was no linear trend linking weight loss at week 20 to subsequent MACE risk, but greater waist circumference reduction at week 20 was associated with lower subsequent MACE risk, and waist circumference reduction by week 104 was associated with lower in-trial risk of MACE. An estimated 33% of the observed benefit on MACE was mediated through waist circumference reduction (HR 0·86 [95% CI 0·77-0·97] after adjustment for time-varying changes in waist circumference).

INTERPRETATION
The cardioprotective effects of semaglutide were independent of baseline adiposity and weight loss and had only a small association with waist circumference, suggesting some mechanisms for benefit beyond adiposity reduction.

FUNDING
Novo Nordisk.


Variations between women and men in risk factors, treatments, cardiovascular disease incidence, and death in 27 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.

Abstract:
BACKGROUND
Some studies, mainly from high-income countries (HICs), report that women receive less care (investigations and treatments) for cardiovascular disease than do men and might have a higher risk of death. However, very few studies systematically report risk factors, use of primary or secondary prevention medications, incidence of cardiovascular disease, or death in populations drawn from the community. Given that most cardiovascular disease occurs in low-income and middle-income countries (LMICs), there is a need for comprehensive information comparing treatments and outcomes between women and men in HICs, middle-income countries, and low-income countries from community-based population studies.

METHODS
In the Prospective Urban Rural Epidemiological study (PURE), individuals aged 35-70 years from urban and rural communities in 27 countries were considered for inclusion. We recorded information on participants' sociodemographic characteristics, risk factors, medication use, cardiac investigations, and interventions. 168 490 participants who enrolled in the first two of the three phases of PURE were followed up prospectively for incident cardiovascular disease and death.

FINDINGS
From Jan 6, 2005 to May 6, 2019, 202 072 individuals were recruited to the study. The mean age of women included in the study was 50·8 (SD 9·9) years compared with 51·7 (10) years for men. Participants were followed up for a median of 9·5 (IQR 8·5-10·9) years. Women had a lower cardiovascular disease risk factor burden using two different risk scores (INTERHEART and Framingham). Primary prevention strategies, such as adoption of several healthy lifestyle behaviours and use of proven medicines, were more frequent in women than men. Incidence of cardiovascular disease (4·1 [95% CI 4·0-4·2] for women vs 6·4 [6·2-6·6] for men per 1000 person-years; adjusted hazard ratio [aHR] 0·75 [95% CI 0·72-0·79]) and all-cause death (4·5 [95% CI 4·4-4·7] for women vs 7·4 [7·2-7·7] for men per 1000 person-years; aHR 0·62 [95% CI 0·60-0·65]) were also lower in women. By contrast, secondary prevention treatments, cardiac investigations, and coronary revascularisation were less frequent in women than men with coronary artery disease in all groups of countries. Despite this, women had lower risk of recurrent cardiovascular disease events (20·0 [95% CI 18·2-21·7] versus 27·7 [95% CI 25·6-29·8] per 1000 person-years in men, adjusted hazard ratio 0·73 [95% CI 0·64-0·83]) and women had lower 30-day mortality after a new cardiovascular disease event compared with men (22% in women versus 28% in men; p<0·0001). Differences between women and men in treatments and outcomes were more marked in LMICs with little differences in HICs in those with or without previous cardiovascular disease.

INTERPRETATION
Treatments for cardiovascular disease are more common in women than men in primary prevention, but the reverse is seen in secondary prevention. However, consistently better outcomes are observed in women than in men, both in those with and without previous cardiovascular disease. Improving cardiovascular disease prevention and treatment, especially in LMICs, should be vigorously pursued in both women and men.

FUNDING
Full funding sources are listed at the end of the paper (see Acknowledgments).


Elevated LDL cholesterol and increased risk of myocardial infarction and atherosclerotic cardiovascular disease in individuals aged 70-100 years: a contemporary primary prevention cohort.

Abstract:
BACKGROUND
Findings of historical studies suggest that elevated LDL cholesterol is not associated with increased risk of myocardial infarction and atherosclerotic cardiovascular disease in patients older than 70 years. We aimed to test this hypothesis in a contemporary population of individuals aged 70-100 years.

METHODS
We included in our analysis individuals (aged 20-100 years) from the Copenhagen General Population Study (CGPS) who did not have atherosclerotic cardiovascular disease or diabetes at baseline and who were not taking statins. Standard hospital assays were used to measure LDL cholesterol. We calculated hazard ratios (HRs) and absolute event rates for myocardial infarction and atherosclerotic cardiovascular disease, and we estimated the number needed to treat (NNT) in 5 years to prevent one event.

FINDINGS
Between Nov 25, 2003, and Feb 17, 2015, 91 131 individuals were enrolled in CGPS. During mean 7·7 (SD 3·2) years of follow-up (to Dec 7, 2018), 1515 individuals had a first myocardial infarction and 3389 had atherosclerotic cardiovascular disease. Risk of myocardial infarction per 1·0 mmol/L increase in LDL cholesterol was augmented for the overall population (HR 1·34, 95% CI 1·27-1·41) and was amplified for all age groups, particularly those aged 70-100 years. Risk of atherosclerotic cardiovascular disease was also raised per 1·0 mmol/L increase in LDL cholesterol overall (HR 1·16, 95% CI 1·12-1·21) and in all age groups, particularly those aged 70-100 years. Risk of myocardial infarction was also increased with a 5·0 mmol/L or higher LDL cholesterol (ie, possible familial hypercholesterolaemia) versus less than 3·0 mmol/L in individuals aged 80-100 years (HR 2·99, 95% CI 1·71-5·23) and in those aged 70-79 years (1·82, 1·20-2·77). Myocardial infarction and atherosclerotic cardiovascular disease events per 1000 person-years for every 1·0 mmol/L increase in LDL cholesterol were highest in individuals aged 70-100 years, with number of events lower with younger age. The NNT in 5 years to prevent one myocardial infarction or atherosclerotic cardiovascular disease event if all people were given a moderate-intensity statin was lowest for individuals aged 70-100 years, with the NNT increasing with younger age.

INTERPRETATION
In a contemporary primary prevention cohort, people aged 70-100 years with elevated LDL cholesterol had the highest absolute risk of myocardial infarction and atherosclerotic cardiovascular disease and the lowest estimated NNT in 5 years to prevent one event. Our data are important for preventive strategies aimed at reducing the burden of myocardial infarction and atherosclerotic cardiovascular disease in the growing population aged 70-100 years.

FUNDING
None.


Xanthine oxidase inhibition for cardiovascular disease prevention.


The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries: the PURE study.


Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study.


The rise and fall of aspirin in the primary prevention of cardiovascular disease.

Abstract: Aspirin is one of the most frequently used drugs worldwide and is generally considered effective for the secondary prevention of cardiovascular disease. By contrast, the role of aspirin in primary prevention of cardiovascular disease is controversial. Early trials evaluating aspirin for primary prevention, done before the turn of the millennium, suggested reductions in myocardial infarction and stroke (although not mortality), and an increased risk of bleeding. In an effort to balance the risks and benefits of aspirin, international guidelines on primary prevention of cardiovascular disease have typically recommended aspirin only when a substantial 10-year risk of cardiovascular events exists. However, in 2018, three large randomised clinical trials of aspirin for the primary prevention of cardiovascular disease showed little or no benefit and have even suggested net harm. In this narrative Review, we reappraise the role of aspirin in primary prevention of cardiovascular disease, contextualising data from historical and contemporary trials.


Antiplatelet therapy for secondary prevention of cardiovascular disease: challenging the certainties.


World Heart Day 2021: COVID-19, digital health, and tackling cardiovascular disease


Polypills with or without aspirin for primary prevention of cardiovascular disease.


Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial

Abstract: Summary Background The use of aspirin in the primary prevention of cardiovascular events remains controversial. We aimed to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first cardiovascular event. Methods ARRIVE is a randomised, double-blind, placebo-controlled, multicentre study done in seven countries. Eligible patients were aged 55 years (men) or 60 years (women) and older and had an average cardiovascular risk, deemed to be moderate on the basis of the number of specific risk factors. We excluded patients at high risk of gastrointestinal bleeding or other bleeding, or diabetes. Patients were randomly assigned (1:1) with a computer-generated randomisation code to receive enteric-coated aspirin tablets (100 mg) or placebo tablets, once daily. Patients, investigators, and others involved in treatment or data analysis were masked to treatment allocation. The primary efficacy endpoint was a composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischaemic attack. Safety endpoints were haemorrhagic events and incidence of other adverse events, and were analysed in the intention-to-treat population. This study is registered with ClinicalTrials. gov, number NCT00501059. Findings Between July 5, 2007, and Nov 15, 2016, 12 546 patients were enrolled and randomly assigned to receive aspirin (n=6270) or placebo (n=6276) at 501 study sites. Median follow-up was 60 months. In the intention-to-treat analysis, the primary endpoint occurred in 269 (4·29%) patients in the aspirin group versus 281 (4·48%) patients in the placebo group (hazard ratio [HR] 0·96; 95% CI 0·81–1·13; p=0·6038). Gastrointestinal bleeding events (mostly mild) occurred in 61 (0·97%) patients in the aspirin group versus 29 (0·46%) in the placebo group (HR 2·11; 95% CI 1·36–3·28; p=0·0007). The overall incidence rate of serious adverse events was similar in both treatment groups (n=1266 [20·19%] in the aspirin group vs n=1311 [20·89%] in the placebo group. The overall incidence of adverse events was similar in both treatment groups (n=5142 [82·01%] vs n=5129 [81·72%] in the placebo group). The overall incidence of treatment-related adverse events was low (n=1050 [16·75%] vs n=850 [13·54%] in the placebo group; p<0·0001). There were 321 documented deaths in the intention-to-treat population (n=160 [2·55%] vs n=161 [2·57%] of 6276 patients in the placebo group). Interpretation The event rate was much lower than expected, which is probably reflective of contemporary risk management strategies, making the study more representative of a low-risk population. The role of aspirin in primary prevention among patients at moderate risk could therefore not be addressed. Nonetheless, the findings with respect to aspirin’s effects are consistent with those observed in the previously published low-risk primary prevention studies. Funding Bayer.


Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study.


Excess mortality and cardiovascular disease in type 1 diabetes in relation to age at onset: a nationwide study of 27,195 young adults with diabetes

Abstract: Background We compared individuals with type 1 diabetes (T1D) to matched controls in order to examine how age at diagnosis of T1D relates to excess mortality and cardiovascular (CV) risk. Methods We studied 27,195 persons with T1D in the Swedish National Diabetes Registry, and 135,178 matched controls from the general population. Using Cox regression, and with adjustment for diabetes duration, we estimated excess risk of all-cause mortality, CV mortality, non-CV mortality, acute myocardial infarction (AMI), stroke, CVD (AMI and stroke), coronary heart disease (CHD), heart failure (HF) and atrial fibrillation (AF). Individuals with T1D were categorized into five groups, according to age at diagnosis: 0–9, 10–14, 15–19, 20–24 and 25–30 years. Findings A total of 27,195 persons with T1D and 135,178 controls were included; 924 persons with T1D and 1,405 controls died during follow-up, of which median was 10 years. Patients who developed T1D at 0–10 years of age displayed hazard ratios (95% CI) of 4.11 (3.24–5.22) for death, 7.38 (3.65–14.94) for CV death, 11.44 (7.95–16.44) for CVD, 30.50 (19.98–46.57) for CHD, 30.95 (17.59–54.45) for AMI, 6.45 (4.04–10.31) for stroke, 12.90 (7.30–22.51) for HF and 1.17 (0.62–2.20) for AF. Corresponding figures for those who developed T1D in the age-range 26–30 were 2.83 (2.38–3.37) for death, 3.64 (2.34–5.66) for CV death, 3.85 (3.05–4.87) for CVD, 6.08 (4.71–7.84) for CHD, 5.77 (4.08–8.16) for AMI, 3.22 (2.35–4.42) for stroke and 5.07 (3.55–7.22) for HF; hence excess risk differed up to 5-fold across the diagnosis age. The highest overall incidence rate, noted for all-cause mortality, was 1.9 (95% CI 1.71 to 2.11) per 100.000 person-years for patients with T1D. Developing T1D before 10 years of age resulted in a loss of 17.7 and 14.2 life years for women and men, respectively, whereas years lost were 10.1 and 9.4 in those diagnosed between 26-30 years of age. Interpretation Age at onset of type 1 diabetes is an important determinant of survival, as well as all cardiovascular outcomes, with highest excess risk in females. Greater focus on cardioprotection maybe warranted in those with early onset T1D. Funding Swedish Heart and Lung Foundation


Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial.

Abstract:
BACKGROUND
Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure.

METHODS
The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597.

FINDINGS
Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype.

INTERPRETATION
In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group.

FUNDING
Novo Nordisk.


Global, regional, and national burden of chronic kidney disease in adults, 1990-2023, and its attributable risk factors: a systematic analysis for the Global Burden of Disease Study 2023.

Abstract:
BACKGROUND
Chronic kidney disease (CKD) is common and ranks among the leading causes of mortality and morbidity. This analysis aimed to present global CKD estimates using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to inform evidence-based policies for CKD identification and treatment.

METHODS
This analysis focused on adults aged 20 years and older over the period 1990 to 2023, from 204 countries and territories. Data sources used were published literature, vital registration systems, kidney failure treatment registries, and household surveys. Estimates of CKD burden, including deaths, incidence, prevalence, and disability-adjusted life-years (DALYs), were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool. A comparative risk assessment approach estimated the proportion of cardiovascular deaths attributable to impaired kidney function and estimated risk factors for CKD.

FINDINGS
Globally, in 2023, 788 million (95% uncertainty interval 743-843) people aged 20 years and older were estimated to have CKD, up from 378 million (354-407) in 1990. The global age-standardised prevalence of CKD in adults was 14·2% (13·4-15·2), a relative rise of 3·5% (2·7-4·1) from 1990. The region with the highest age-standardised prevalence was north Africa and the Middle East (18·0%; 16·9-19·4). Most people had stage 1-3 CKD, with a combined prevalence of 13·9% (13·1-15·0). In 2023, CKD was the ninth leading cause of death globally, accounting for 1·48 million (1·30-1·65) deaths, and the 12th leading cause of DALYs, with an age-standardised DALY rate of 769·2 (691·8-857·4) per 100 000. Impaired kidney function as a risk factor accounted for 11·5% (8·4-14·5) of cardiovascular deaths. High fasting plasma glucose, body-mass index, and systolic blood pressure were all leading risk factors for CKD DALYs.

INTERPRETATION
CKD is a major global health issue, with rising prevalence and increasing importance as a cause of death and as a risk factor for cardiovascular death. A better understating of aetiology, appropriate screening, and implementation programmes are needed to translate advances in CKD treatment into improved patient outcomes.

FUNDING
Gates Foundation, Wellcome, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.


Eligibility and subsequent burden of cardiovascular disease of four strategies for blood pressure-lowering treatment: a retrospective cohort study

Abstract: Summary Background Worldwide treatment recommendations for lowering blood pressure continue to be guided predominantly by blood pressure thresholds, despite strong evidence that the benefits of blood pressure reduction are observed in patients across the blood pressure spectrum. In this study, we aimed to investigate the implications of alternative strategies for offering blood pressure treatment, using the UK as an illustrative example. Methods We did a retrospective cohort study in primary care patients aged 30–79 years without cardiovascular disease, using data from the UK's Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality. We assessed and compared four different strategies to determine eligibility for treatment: using 2011 UK National Institute for Health and Care Excellence (NICE) guideline, or proposed 2019 NICE guideline, or blood pressure alone (threshold ≥140/90 mm Hg), or predicted 10-year cardiovascular risk alone (QRISK2 score ≥10%). Patients were followed up until the earliest occurrence of a cardiovascular disease diagnosis, death, or end of follow-up period (March 31, 2016). For each strategy, we estimated the proportion of patients eligible for treatment and number of cardiovascular events that could be prevented with treatment. We then estimated eligibility and number of events that would occur during 10 years in the UK general population. Findings Between Jan 1, 2011, and March 31, 2016, 1 222 670 patients in the cohort were followed up for a median of 4·3 years (IQR 2·5–5·2). 271 963 (22·2%) patients were eligible for treatment under the 2011 NICE guideline, 327 429 (26·8%) under the proposed 2019 NICE guideline, 481 859 (39·4%) on the basis of a blood pressure threshold of 140/90 mm Hg or higher, and 357 840 (29·3%) on the basis of a QRISK2 threshold of 10% or higher. During follow-up, 32 183 patients were diagnosed with cardiovascular disease (overall rate 7·1 per 1000 person-years, 95% CI 7·0–7·2). Cardiovascular event rates in patients eligible for each strategy were 15·2 per 1000 person-years (95% CI 15·0–15·5) under the 2011 NICE guideline, 14·9 (14·7–15·1) under the proposed 2019 NICE guideline, 11·4 (11·3–11·6) with blood pressure threshold alone, and 16·9 (16·7–17·1) with QRISK2 threshold alone. Scaled to the UK population, we estimated that 233 152 events would be avoided under the 2011 NICE guideline (28 patients needed to treat for 10 years to avoid one event), 270 233 under the 2019 NICE guideline (29 patients), 301 523 using a blood pressure threshold (38 patients), and 322 921 using QRISK2 threshold (27 patients). Interpretation A cardiovascular risk-based strategy (QRISK2 ≥10%) could prevent over a third more cardiovascular disease events than the 2011 NICE guideline and a fifth more than the 2019 NICE guideline, with similar efficiency regarding number treated per event avoided. Funding National Institute for Health Research.


Association of dairy intake with cardiovascular disease and mortality in 21 countries from five continents (PURE): a prospective cohort study.

Abstract:
BACKGROUND
Dietary guidelines recommend minimising consumption of whole-fat dairy products, as they are a source of saturated fats and presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Evidence for this contention is sparse and few data for the effects of dairy consumption on health are available from low-income and middle-income countries. Therefore, we aimed to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease.

METHODS
The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35-70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre.

FINDINGS
Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9·1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0·84, 95% CI 0·75-0·94; ptrend=0·0004), total mortality (0·83, 0·72-0·96; ptrend=0·0052), non-cardiovascular mortality (0·86, 0·72-1·02; ptrend=0·046), cardiovascular mortality (0·77, 0·58-1·01; ptrend=0·029), major cardiovascular disease (0·78, 0·67-0·90; ptrend=0·0001), and stroke (0·66, 0·53-0·82; ptrend=0·0003). No significant association with myocardial infarction was observed (HR 0·89, 95% CI 0·71-1·11; ptrend=0·163). Higher intake (>1 serving vs no intake) of milk (HR 0·90, 95% CI 0·82-0·99; ptrend=0·0529) and yogurt (0·86, 0·75-0·99; ptrend=0·0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0·88, 0·76-1·02; ptrend=0·1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1·09, 95% CI 0·90-1·33; ptrend=0·4113).

INTERPRETATION
Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort.

FUNDING
Full funding sources are listed at the end of the paper (see Acknowledgments).


A comprehensive review on direct air carbon capture (DAC) technology by adsorption: From fundamentals to applications


Atmospheric alchemy: The energy and cost dynamics of direct air carbon capture

Abstract: Amid a relentless global climate crisis, the 28th Conference of the Parties (COP28) spotlighted Direct Air Carbon Capture (DACC) as a key intervention to mitigate escalating temperatures and CO2 levels. The Intergovernmental Panel on Climate Change (IPCC) underscores the urgency of this challenge, stipulating the need for robust CO2 removal strategies. It sets a daunting yet crucial target: capture 85 million metric tons of CO2 by 2030, escalating to 980 million metric tons by 2050, to achieve net-zero emissions (IEA, Executive Summary—Direct Air Capture 2022—Analysis. https://www.iea.org/reports/direct-air-capture-2022/executive-summary). Despite this imperative, the existing 19 operational DAC facilities globally face significant barriers, including prohibitive costs and stringent regulations, which impede their large-scale application (Ozkan et al.). Current status and pillars of direct air capture technologies. Iscience (2022). While COP28 stopped short of delineating a definitive roadmap for DAC, this article addresses a vital aspect of this technology: DAC processes’ substantial energy and heat requirements, which are integral to their operational efficiency and economic viability. This article illuminates pathways for future technological evolution and cost optimization through an in-depth analysis of these requirements, thereby charting a course toward a more effective and scalable DAC infrastructure. With atmospheric CO2 exceeding 420 ppm, the clock is ticking on the climate crisis. DAC offers a revolutionary approach to directly remove this excess CO2, acting as a critical tool in our fight for a sustainable future. However, current DAC systems face the challenge of high energy consumption. Continuous fan operation for air intake and sorbent material regeneration, consuming nearly 2000–3000 kWh per ton of CO2 captured, are major contributors. Optimizing these processes is crucial. Advancements in sorbent efficiency, system design that minimizes parasitic energy losses, and seamless integration with renewable energy sources are key to slashing DAC’s energy demands. By reducing its carbon footprint and enhancing economic viability, these advancements can unlock the full potential of DAC to become a game-changer in combating climate change and securing a cleaner future for our planet. Given the significant energy and heat requirements of DACC processes, what technological innovations are necessary to make these systems more energy efficient and economically viable? Considering the substantial energy demands of DACC processes, what are the most promising avenues for reducing these requirements to enhance the technology's scalability and cost-effectiveness? How can current technological limitations be overcome to scale up DACC effectively? What role could renewable energy sources play in meeting the energy and heat demands of DACC facilities, and how might this integration impact the overall carbon footprint of the carbon capture process? How do the energy and heat requirements of DACC technologies influence their location and infrastructure needs, particularly in relation to energy sources and heat sinks? What technological innovations or advancements are currently being explored to optimize the energy and heat efficiency of DACC processes, and what challenges do they face in terms of implementation and scaling? Given the significant role of DACC in achieving net-zero emissions targets, how can policy and regulatory frameworks be designed to support the development and deployment of energy-efficient DACC solutions?


Enhanced Direct Air Carbon Capture on NaX Zeolite by Electric‐Field Enhanced Physical Adsorption and In Situ CO2 Synergistic Effects of Cold Plasma

Abstract: Direct air carbon capture (DAC) is vital to achieving negative CO2 emissions, with physical adsorption offering a cost‐effective and energy‐efficient solution. an advanced zeolite modification technique is presented using cold plasma, which enhances the CO2 adsorption efficiency of NaX zeolite by 11.5% after just 60 min. This method utilizes the electric field to reorganize cation distribution and pore structure and significantly improve the adsorption capacity, efficiency, and selectivity. Compared to traditional methods, this technique is simpler and more effective, as demonstrated through first‐principles calculations, thermodynamics, kinetics, and adsorption equilibrium studies.


Direct air capture (DAC): molten carbonate direct transformation of airborne CO2 to durable, useful carbon nanotubes and nano-onions

Abstract: The concept and first demonstration of an effective direct air capture molten carbonate chemistry is presented.


Prospective environmental burdens and benefits of fast-swing direct air carbon capture and storage

Abstract: Direct air capture (DAC) in combination with storage of CO2 can lower atmospheric CO2 concentrations. This study investigates the environmental impact of a new fast-swing solid sorbent DAC system, including CO2 transport and storage, over its life cycle, using prospective life cycle assessment. This DAC technology is currently on technology readiness level 5 and is expected to operate on an industrial scale by 2030. The technology was upscaled to the industrial scale and future changes in the background over the lifetime of the system were included, such as electricity grid mix decarbonization. Environmental trade-offs for the new DAC system were assessed by comparing environmental benefits from CO2 sequestration with environmental burdens from production, operation and decommissioning. We considered three electricity generation configurations: grid-connected, wind-connected, and a hybrid configuration. We found net environmental benefits for all configurations and background scenarios for ecosystem damage and climate change. Net human health benefits were observed when the electricity grid decarbonizes quickly and without the use of a battery. The environmental benefits increase with decreasing electricity footprint and are comparable with other DAC technologies. This illustrates that the new DAC system can help to meet the climate goals.


Exploration of a novel electrochemical CN coupling process: Urea synthesis from direct air carbon capture with nitrate wastewater.

Abstract: Direct air capture (DAC) can be used to decrease the CO2 concentration in the atmosphere, but this requires substantial energy consumption. If residual waste carbon (in the form of bicarbonate solution) from DAC can be directly reused, it might present a novel method for overcoming the aforementioned challenges. Electrochemical CN coupling methods for synthesizing urea have garnered considerable attention for waste carbon utilization, but the carbon source is high-purity CO2. No research has been conducted regarding the application of bicarbonate solution as the carbon source. This study proposes a proof-of-concept electrochemical CN coupling process for synthesizing urea using bicarbonate solution from DAC as the carbon source and nitrate from wastewater as the nitrogen source. These results confirmed the feasibility of synthesizing urea using a three-electrode system employing TF and CuInS2/TF as the working electrodes via potentiostatic electrolysis. Under the optimal conditions (initial pH 5.0 and applied potential of -1.3 V vs. Ag/AgCl), the urea yield after 2 h of electrolysis reached 3017.2 μg h-1 mgcat.-1 and an average Faradaic efficiency of 19.6 %. The in-situ attenuated total reflection surface-enhanced infrared absorption spectroscopy indicated a gradual increase in the intensity of the -CONH bond signal on the surface of the CuInS2/TF electrode as the reaction progressed. This implied that this bond may be a key chemical group in this process. The density functional theory calculations demonstrated that *CONH was a pivotal intermediate during CN coupling, and a two-step CN coupling reaction path was proposed. *NH + *CO primarily transformed into *CONH, followed by the conversion reaction of *CONH + *NO to *NOCONH2. This study offers a groundbreaking approach for waste carbon utilization from DAC and holds the potential to furnish technical underpinnings for advancing electrochemical CN coupling methods.


Thermodynamic loss analysis of a liquid-sorbent direct air carbon capture plant

Abstract: Direct air capture of CO 2 is often presented as a promising technology to help mitigate climate change, although proposed processes are highly energy intensive. We analyze Carbon Engineering’s 1 Mt-CO 2 /year natural-gas-powered direct air capture (DAC) process, which requires 273.2 MW per plant, where we ﬁnd that 252 MW are irreversibly lost, corresponding to a second-law efﬁciency of 7.8%. Our component-level analysis details the mechanisms by which these losses of thermodynamic work potential occur in the most energy-intensive plant segments. Here, we emphasize the effects of chemical exergy dissipation in the air contactor, where stored chemical exergy is released as low-grade heat into the environment. Other major losses occur in the calciner and its preheat cyclones due to the high temperature demanded by its internal chemical reaction, as well as in the water knockout system, CO 2 compression system, and power island. Finally, we illustrate the issues arising from the use of natural gas as a feedstock for heat and power, and suggest directions to pursue for further analysis and process improvements, which we consider imperative to make this DAC process a viable option for large-scale CO 2 removal toward IPCC targets.


Facile Fabrication of Monodispersed Carbon Sphere: A Pathway Toward Energy-Efficient Direct Air Capture (DAC) Using Amino Acids.

Abstract: Direct removal of carbon dioxide (CO2 ) from the atmosphere, known as direct air capture (DAC) is attracting worldwide attention as a negative emission technology to control atmospheric CO2 concentrations. However, the energy-intensive nature of CO2 absorption-desorption processes has restricted deployment of DAC operations. Catalytic solvent regeneration is an effective solution to tackle this issue by accelerating CO2 desorption at lower regeneration temperatures. This work reports a one-step synthesis methodology to prepare monodispersed carbon nanospheres (MCSs) using trisodium citrate as a structure-directing agent with acidic sites. The assembly of citrate groups on the surface of MCSs enables consistent spherical growth morphology, reduces agglomeration and enhances water dispersibility. The functionalization-assisted synthesis produces uniform, hydrophilic nanospheres of 100-600 nm range. This work also demonstrates that the prepared MCSs can be further functionalized with strong Brønsted acid sites, providing high proton donation ability. Furthermore, the materials can be effectively used in a wide range of amino acid solutions to substantially accelerate CO2 desorption (25.6% for potassium glycinate and 41.1% for potassium lysinate) in the DAC process. Considering the facile synthesis of acidic MCSs and their superior catalytic efficiency, these findings are expected to pave a new path for energy-efficient DAC.


Direct Air Capture (DAC) for Achieving Net-Zero CO2 Emissions: Advances, Applications, and Challenges

Abstract: Carbon dioxide (CO2), as the primary greenhouse gas, has significant impacts on global climate change, leading to severe and irreversible adverse consequences for ecosystems and human environments. To address the issue of excessive CO2 emissions, efforts in recent years have yielded significant progress in the development of clean energy sources and the promotion of carbon capture, utilization, and storage (CCUS) technologies. Conventional CO2 capture techniques are limited in addressing global atmospheric CO2 excess effectively, as they target only high-concentration CO2 emissions and require implementation at specific emission points. Direct air capture (DAC) technology has emerged as a promising solution due to its flexibility in deployment, avoidance of land competition, and ability to capture legacy CO2 emissions. Additionally, DAC offers opportunities for producing synthetic clean fuels, thereby reducing reliance on traditional fossil fuels and aiding in reducing greenhouse gas emissions. This study provides a comprehensive review of DAC technology, encompassing its principles, technological advancements, real-world applications, challenges, and future research directions. By offering insights into the current state and potential of DAC technology, this study aims to guide global efforts in scaling up DAC deployment, ultimately contributing to achieving global carbon neutrality or even negative emissions.


Measuring and Modeling Water and Carbon Dioxide Adsorption on Amine Functionalized Alumina under Direct Air Capture Conditions

Abstract: Water vapor is an unavoidable component of ambient air that sorbents designed for atmospheric CO2 capture must contend with. Amine functionalized sorbents often exhibit an enhancement of CO2 uptake in the presence of moisture through a variety of mechanisms, and in this work, we investigate the coadsorption of water and CO2 on amine functionalized alumina. Sorbent performance is examined under varying levels of humidity and temperature using three common measurement techniques: gravimetric, volumetric, and breakthrough methods. Our findings show that water increasingly enhances CO2 adsorption up to the monolayer saturation point of water, above which no further enhancement is observed. Competitive adsorption is observed primarily at low relative humidities, and a novel dual-site isotherm model is developed that successfully describes these behaviors. Additionally, this study highlights the unique advantages of each measurement technique for accurately characterizing sorbent performance under direct air capture (DAC) conditions. These insights contribute to the understanding and optimization of amine-based sorbents in DAC applications.

Industrial & Engineering Chemistry Research


A review of direct air capture (DAC): scaling up commercial technologies and innovating for the future

Abstract: Direct air capture (DAC) can provide an impactful, engineered approach to combat climate change by removing carbon dioxide (CO2) from the air. However, to meet climate goals, DAC needs to be scaled at a rapid rate. Current DAC approaches use engineered contactors filled with chemicals to repeatedly capture CO2 from the air and release high purity CO2 that can be stored or otherwise used. This review article focuses on two distinctive, commercial DAC processes to bind with CO2: solid sorbents and liquid solvents. We discuss the properties of solvents and sorbents, including mass transfer, heat transfer and chemical kinetics, as well as how these properties influence the design and cost of the DAC process. Further, we provide a novel overview of the considerations for deploying these DAC technologies, including concepts for learning-by-doing that may drive down costs and material requirements for scaling up DAC technologies.


A new relevant membrane application: CO2 direct air capture (DAC)

Abstract: Since carbon dioxide (CO2) is the primary greenhouse gas emitted due to human activities into the atmosphere, strong research efforts have been developed towards capturing and 2 decreasing its production. Unfortunately, specific processes and activities make it impossible to avoid CO2 emissions. Among the different strategies scientists propose for CO2 reduction, direct CO2 capture from the atmosphere, also known as direct air capture (DAC), represents a promising alternative in which sorbents have been mainly used. Recently, gas separation membranes have also been speculated to carry out such a separation, thanks to their smaller footprint and simpler setup and operation; however, their application remains a proposition in the field. This paper gives a perspective of the ongoing research and attempts of DAC applications via membrane separation and introduces the main membrane materials and types used for CO2 separation. Finally, the process considerations for DAC using membranes are stated to guide the new researchers in the field.


Distributed direct air capture by carbon nanofiber air filters

Abstract: The rising atmospheric CO2 concentration is one of the biggest challenges human civilization faces. Direct air capture (DAC) that removes CO2 from the atmosphere provides great potential in carbon neutralization. However, the massive land use and capital investment of centralized DAC plants and the energy-intensive process of adsorbent regeneration limit its wide employment. We develop a distributed carbon nanofiber (CNF)–based DAC air filter capable of adsorbing CO2 downstream in ventilation systems. The DAC air filter not only has the potential to remove 596 MtCO2 year−1 globally but can also decrease energy consumption in existing building systems. The CNF-based adsorbent has a capacity of 4 mmol/g and can be regenerated via solar thermal or electrothermal methods with low carbon footprints. Through life cycle assessment, the CNF air filter shows a carbon removal efficiency of 92.1% from cradle to grave. Additionally, techno-economic analysis estimates a cost of $209 to 668 in capturing and storing 1 tonne of CO2 from direct air.


Direct air capture-assisted sustainable fuel solution in maritime sector: a carbon footprint perspective

Abstract: Carbon emissions reduction within the maritime sector is pivotal for realizing zero-carbon goals and mitigating climate impacts. Adopting renewable carbon fuels presents a potent strategy. It is necessary to have a comprehensive understanding of its negative carbon attributes and enduring contributions to future development based on carbon footprint assessment. By using the CO2 captured through direct air capture (DAC) technology and the H2 obtained via water electrolysis as feedstock, electro-methanol (e-methanol) can be produced under renewable energy-driven conditions. Owing to the environmental benefits and economic feasibility of e-methanol, we highlight its potential as a practical alternative to traditional fossil fuel-based technical scenarios. A quantitative analysis of this integrated system from a carbon footprint perspective allows for an environmental sustainability assessment. According to predictions, scaled-up usage of the system can reduce the maritime sector's contribution to global carbon emissions by half by 2050. ∙ Using CO2 from DAC and H2 from water electrolysis, e-methanol can be produced and used within the maritime sector. ∙ A quantitative analysis from a carbon footprint perspective allows for an environmental sustainability assessment. ∙ Scaled-up usage of the system can reduce the maritime sector's contribution to global carbon emissions by half by 2050.


Water-Enhanced Direct Air Capture of Carbon Dioxide in Metal-Organic Frameworks.

Abstract: We have developed two series of amine-functionalized zirconium (Zr) metal-organic framework-808 (MOF-808), which were produced by postsynthetic modifications to have either amino acids coordinated to Zr ions (MOF-808-AAs) or polyamines covalently bound to the chloro-functionalized structure (MOF-808-PAs). These MOF variants were comprehensively characterized by liquid-state 1H nuclear magnetic resonance (NMR) measurements and potentiometric acid-base titration to determine the amounts of amines, energy-dispersive X-ray spectroscopy to assess the extent of covalent substitution by polyamines, powder X-ray diffraction analysis to verify the maintenance of the MOF crystallinity and structure after postsynthetic modifications, nitrogen sorption isotherm measurements to confirm retention of the porosity, and water sorption isotherm measurements to find the water uptake in the pores of each member of the series. Evaluation and testing of these compounds in direct air capture (DAC) of CO2 showed improved CO2 capture performance for the functionalized forms, especially under humid conditions: In dry conditions, the l-lysine- and tris(3-aminopropyl)amine-functionalized variants, termed as MOF-808-Lys and MOF-808-TAPA, exhibited the highest CO2 uptakes at 400 ppm, measuring 0.612 and 0.498 mmol g-1, and further capacity enhancement was achieved by introducing 50% relative humidity, resulting in remarkable uptakes of 1.205 and 0.872 mmol g-1 corresponding to 97 and 75% increase compared to the dry uptakes, respectively. The mechanism underlying the enhanced uptake efficiency was revealed by 13C solid-state NMR and temperature-programmed desorption measurements, indicating the formation of bicarbonate species, and therefore a stoichiometry of 1:1 CO2 to each amine site.

Journal of the American Chemical Society


Distributed direct air capture of carbon dioxide by synergistic water harvesting

Abstract: Adsorption-based direct air capture (DAC) of carbon dioxide, using chemisorbents like solid amines, has been widely recognized as a sustainable measure to contain atmospheric CO2 concentrations. However, the productivity and economic viability of DAC have been compromised by the high energy consumption for regenerating the adsorbents. Here, we show that by synergistically harvesting water and carbon dioxide from the atmosphere, we can regenerate the unit using in situ vapor purge at low energy and capital cost. The desorption of CO2 is substantially enhanced in the presence of concentrated water vapors at around 100 °C, concurrently producing 97.7% purity CO2 and fresh water without the use of vacuum pumps and steam boilers. Moreover, we demonstrate that the DAC prototype can also be powered by sunlight, which recovers 98% of the adsorbed CO2, with 20% less energy demand, enabling sustainable carbon capture from air in a real distributed manner. Direct air capture of CO2 suffers from high energy consumption. Here, the authors use co-harvested water as in situ vapor purge to regenerate the sorbents, achieving over 98% recovery of the adsorbed CO2, more than 20% reduction in energy penalty, and synergistic production of CO2 and water.


A Comparative Study of Different Sorbents in the Context of Direct Air Capture (DAC): Evaluation of Key Performance Indicators and Comparisons

Abstract: Direct air capture can be based on an adsorption system, and the used sorbent (chemisorbents or physisorbents) influences process. In this work, two amine-functionalized sorbents, as chemisorbents, and three different metal organic frameworks, as physisorbents, are considered and compared in terms of some key performance indicators. This was carried out by developing a mathematical model describing the adsorption and desorption stages. An independent analysis was carried out in order to verify data reported in the literature. Results show that the equilibrium loading is a critical parameter for adsorption capacity, energy consumption, and cost. The considered metal organic frameworks are characterized by a lower equilibrium loading (10−4 mol/kg) compared to chemisorbents (10−1 mol/kg). For this reason, physisorbents have higher overall energy consumptions and costs, while capturing a lower amount of carbon dioxide. A reasonable agreement is found on the basis of the operating conditions of the Climeworks company, modelling the use of the same amine cellulose-based sorbent. The same order of magnitude is found for total costs (751 USD/tonneCO2 for our analysis, compared to the value of 600 USD/tonneCO2 proposed by this company).


Direct air capture integration with low-carbon heat: Process engineering and power system analysis

Abstract: Direct air capture (DAC) of carbon dioxide (CO 2 ) is energy intensive given the low concentration ( < 0.1%) of CO 2 in ambient air, but offers relatively strong verification of removals and limited land constraints to scale. Lower temperature solid sorbent based DAC could be coupled on-site with low carbon thermal generators such as nuclear power plants. Here, we undertake a unique interdisciplinary study combining process engineering with a detailed macro-energy system optimization model to evaluate the system-level impacts of such plant designs in the Texas electricity system. We contrast this with using grid power to operate a heat pump to regenerate the sorbent. Our analysis identifies net carbon removal costs accounting for power system impacts and resulting indirect CO 2 emissions from DAC energy consumption. We find that inefficient configurations of DAC at a nuclear power plant can lead to increases in power sector emissions relative to a case without DAC, at a scale that would cancel out almost 50% of the carbon removal from DAC. Net removal costs for the most efficient configurations increase by roughly 18% once indirect power system-level impacts are considered, though this is comparable to the indirect systems-level emissions from operating grid-powered heat pumps for sorbent regeneration. Our study therefore highlights the need for DAC energy procurement to be guided by consideration of indirect emission impacts on the electricity system. Finally, DAC could potentially create demand pull for zero carbon firm generation, accelerating decarbonization relative to a world without such DAC deployment. We find that DAC operators would have to be willing to pay existing or new nuclear power plants roughly $30–80/tCO 2 or $150–400/tCO 2 respectively, for input energy, to enable nuclear plants to be economically competitive in least cost electricity markets that do not have carbon constraints or subsidies for nuclear energy.


Activated Carbon Fiber Felt Composites for the Direct Air Capture of Carbon Dioxide.

Abstract: Negative emission technologies to mitigate climate change require innovative solutions for the direct air capture (DAC) of CO2 from the atmosphere. K2CO3 readily reacts with CO2 to form KHCO3; however, bulk K2CO3 suffers from very slow sorption kinetics. By incorporating K2CO3 into activated carbon (AC) fiber felts, the sorption kinetics were significantly improved by increasing the surface area of K2CO3 in contact with air. The AC-K2CO3 fiber composite felts are flexible, cheap, easy to manufacture, chemically stable, and show excellent DAC capacity and (de)sorption rates, with stable performance up to ten cycles. Cyclic testing was demonstrated with 4 h sorption and 0.5 h desorption intervals. The best composite felts collected an average of 478 µmol of CO2 per gram of composite during 4 h of exposure to ambient air (19% relative humidity) that had a CO2 concentration of 400-450 ppm after regeneration at 125 °C in an air furnace. An increase in the dew point temperature from 0 °C to 12 °C decreased sorption performance of the composite felts by 40%.


Study of Direct Air Capture (DAC) Using a KOH/K2CO3 Absorbing Solution for CO2 Capture

Abstract: Direct Air Capture (DAC) consists of sequestrating CO 2 from ambient air using absorption or adsorption mechanisms. Within the former, alkaline solutions, such as KOH, are generally used as the absorbing agent due to the high reached pH values favouring CO 2 absorption. However, these solutions' alkalinity induces high corrosivity and harmful properties, making them challenging to handle. The KOH/K 2 CO 3 mixture solution is studied in this paper and proposed as an alternative to the more generally used strong base solution. This mixture solution aims at taking advantage of the low toxicity and corrosivity of K 2 CO 3 solutions while still including a fraction of KOH. It guarantees sufficiently high alkalinity and counteracts K 2 CO 3 poor mass transfer performance. The purpose of this paper is to have first estimations of the potential of KOH/K 2 CO 3 solutions as the absorbing agent for carbon capture in ambient air by taking only equilibrium considerations and assuming an ideal aqueous solution. Within this framework, CO 2 removal efficiencies are calculated for various pH values and phase ratios, and then the results are compared with literature data. This comparison highlights the importance of kinetics limitations for CO 2 absorption in aqueous solutions. A significant part of this work is focused on the potential precipitation issues that may occur during CO 2 absorption. These issues’ likelihood is compared for the case of a KOH/K 2 CO 3 and a NaOH/K 2 CO 3 solution. It turns out that precipitation is only encountered in the latter situation when extreme concentration conditions are encountered. In further work, the results should be refined by including the absorption kinetics and appropriately modelling the aqueous phase, accounting for the existing interactions. These factors may influence the conditions under which precipitation occurs. Nevertheless, the present study gives the necessary thermodynamics fundamental knowledge for addressing the challenges to be encountered in KOH/K 2 CO 3 solutions.


Architecting Metal-Organic Frameworks at Molecular Level toward Direct Air Capture.

Abstract: Escalating carbon dioxide (CO2) emissions have intensified the greenhouse effect, posing a significant long-term threat to environmental sustainability. Direct air capture (DAC) has emerged as a promising approach to achieving a net-zero carbon future, which offers several practical advantages, such as independence from specific CO2 emission sources, economic feasibility, flexible deployment, and minimal risk of CO2 leakage. The design and optimization of DAC sorbents are crucial for accelerating industrial adoption. Metal-organic frameworks (MOFs), with high structural order and tunable pore sizes, present an ideal solution for achieving strong guest-host interactions under trace CO2 conditions. This perspective highlights recent advancements in using MOFs for DAC, examines the molecular-level effects of water vapor on trace CO2 capture, reviews data-driven computational screening methods to develop a molecularly programmable MOF platform for identifying optimal DAC sorbents, and discusses scale-up and cost of MOFs for DAC.