Prevention Of Atherosclerotic Cardiovascular Disease Research Articles

Quality of care for secondary cardiovascular disease prevention in 2009–2017: population-wide cohort study of antiplatelet therapy use in Scotland

BackgroundAntiplatelet therapy (APT) can substantially reduce the risk of further vascular events in individuals with established atherosclerotic cardiovascular disease (ASCVD). However, knowledge regarding the extent and determinants of APT use...

Rethinking atherosclerotic cardiovascular disease prevention in the era of expanding therapies: could plaque stabilization reduce the need for lifelong treatments and polypharmacy?

This review examines current evidence on pharmacologically induced plaque stabilization in the context of a growing range of new therapies. It explores the potential for a paradigm shift in atherosclerotic cardiovascular disease (ASCVD) prevention, where treatments may not need to be lifelong to achieve lasting benefits. Since 2015, over 14 novel therapies have been introduced, each shown to reduce ASCVD risk when added to standard care with statins and aspirin. More than 80% of ischemic heart disease patients are now eligible for one or more of these treatments, increasing the risk of polypharmacy, treatment burden, and adverse side effects. As more therapies become available, this challenge is expected to grow. Many of these treatments have demonstrated plaque regression and stabilization, as evidenced by both intravascular ultrasound and computed tomography angiography, which likely explains much of their efficacy. The increasing number of novel therapies presents challenges in preventing ASCVD without leading to lifelong polypharmacy and increased patient burden. Since many of these drugs act through plaque stabilization, a new approach may be feasible - using these treatments for shorter durations to induce plaque regression, followed by less intensive maintenance therapies to preserve stability. This approach warrants further investigation in future studies.

Association between colchicine use and adverse cardiovascular events in patients with gout: a nationwide nested case-control study.

The association between colchicine use and the primary prevention of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to explore the association between colchicine use and new development of ASCVD and ASCVD-related mortality in patients with incident gout. This nested case-control study utilized the nation-wide claims database of the Korean National Health Insurance System. Patients without a history of ASCVD who developed incident gout and were newly started on allopurinol as first-line therapy between 2011 and 2016 were initially screened. Individuals who experienced ASCVD event or ASCVD-related mortality during the follow-up period were matched with four controls for age, sex, income, residential area, co-morbidities, and medications. The main exposure was colchicine use, assessed by 1) the cumulative defined daily doses (cDDDs) and 2) the cumulative duration. For secondary analyses, the risk of ASCVD events and ASCVD-related mortality were examined, separately. Overall, 9,346 patients with ASCVD event or ASCVD-related mortality were matched with 35 070 controls. The patient population was predominantly male. Compared with non-users, a curvilinear relationship between higher cDDDs of colchicine and the odds of ASCVD event was observed; the odds ratios (95% confidence interval) were were 1.09 (1.04-1.15) for <90 cDDDs, 1.20 (1.07-1.33) for 80-179 cDDDs, and 1.21 (1.09-1.35) for ≥180 cDDDs. This association was similarly observed for ASCVD events and ASCVD-related mortality, respectively. Colchicine use was associated with an increased risk of ASCVD in patients with newly diagnosed gout who did not have a prior history of ASCVD.

Financial resources, access to care, and quality of care mediate racial disparities in statin usage for secondary prevention.

There are disparities in statin therapy for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). The role of structural racism in this disparity has not been examined. This is a cross-sectional study of participants with ASCVD in the Medical Expenditure Panel Survey from 2014-2017. Mediation analysis is utilized to estimate the direct effect of race and indirect effect of financial resources, access to care, and quality of care on statin usage. The proportion of participants using statins by race/ethnicity were 58.5% for non-Hispanic Whites, 45% for Hispanics, 48.6% for Blacks, 61.6% for Asians, and 46.8% for Others. Statin usage was lower for Hispanics (OR = 0.79, 95% confidence interval [0.65-0.96]) and Blacks (OR = 0.80 [0.66-0.95]) compared to Whites. Hispanic, Black, and Other participants with the same financial resources, access to care, and quality of care as White participants did not have significantly different statin usage compared to White participants (Hispanic: OR = 0.98 [0.79-1.13]; Black (OR = 0.88 [0.76-1.06], Other: OR 0.76, 95% CI [0.56-1.15]). Hispanic, Black, and Other participants had significantly lower statin usage than subjects of the same race but with financial resources, access to care, and quality of care observed in White subjects (Hispanic: OR = 0.83 [0.83-0.92]; Black: OR = 0.91[0.88-0.94]; Other: OR = 0.92 [0.87-0.98]). The indirect effect of race and ethnicity on statin therapy are significant but the direct effect of race and ethnicity on statin therapy are insignificant among Blacks and Hispanics compared to non-Hispanic Whites. This suggests that racial disparities in statin therapy are mediated through inequitably distributed resources, suggestive of the impact of structural racism.

Diabetes Risk Factors in People With HIV Receiving Pitavastatin Versus Placebo for Cardiovascular Disease Prevention : A Randomized Trial.

REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) led to new guidelines for statin use among people with HIV (PWH) with low to moderate risk for atherosclerotic cardiovascular disease (ASCVD). Little is known about the natural history of diabetes mellitus (DM) or mechanisms contributing to statin effects on DM among this population. To determine the contribution of known DM risk factors to excess risk for DM with pitavastatin in REPRIEVE. Phase 3, primary ASCVD prevention trial over a median of 5.6 years of follow-up. (ClinicalTrials.gov: NCT02344290). Global, multicenter trial. 7731 PWH aged 40 to 75 years with low to moderate ASCVD risk (by the pooled cohort equations from the American College of Cardiology and American Heart Association) without DM at study entry. Random 1:1 assignment to pitavastatin, 4 mg daily, or placebo. New-onset DM was determined at each visit by clinical diagnosis requiring initiation of medication treatment for DM. The incidence of new-onset DM was assessed in relation to predefined demographic and metabolic risk factors, stratified by treatment group. Treatment effects of pitavastatin on progression to new DM in key subgroups were determined. Participants with at least 3 DM risk factors (vs. no risk factors) had increased risk for DM in each treatment group (incidence rate, 3.24 per 100 person-years [PY] vs. 0.34 per 100 PY [pitavastatin] and 2.66 per 100 PY vs. 0.27 per 100 PY [placebo]). The incidence of DM was highest in South Asia. In adjusted analyses, high body mass index, prediabetes, and metabolic syndrome components were strongly associated with new-onset DM (all P < 0.005). Pitavastatin was the only statin assessed; DM was assessed clinically. Metabolic risk factors, including prediabetes and obesity, contributed to new-onset DM in statin- and placebo-treated participants. A clinically significant effect of pitavastatin on DM was seen primarily among those with multiple risk factors for DM at entry. Strategies targeting key metabolic risk factors, like obesity and prediabetes, may help protect against DM among PWH. National Heart, Lung, and Blood Institute of the National Institutes of Health.

Serum Lipoprotein(a) Levels and Their Association with Atherosclerotic Cardiovascular Disease in Japan.

To investigate the distribution of lipoprotein(a) (Lp(a)) and its association with atherosclerotic cardiovascular disease (ASCVD) in Japanese patients at high risk for ASCVD using a health insurance database. Between July 2013 and June 2021, patients eligible for ASCVD prevention according to the 2017 Japan Atherosclerosis Society (JAS) guidelines with documented Lp(a) test results were extracted from the Medical Data Vision claims database and divided into three groups: primary prevention high-risk (Group I), secondary prevention (Group II) and secondary prevention high-risk (Group III). Data on lipid levels, cardiovascular morbidity risk factors and lipid-lowering treatments were extracted. Of 700,580 patients with documented low-density lipoprotein cholesterol (LDL-C), 2,967 (0.42%) were tested for Lp(a). In 2,170 eligible patients, the median [interquartile range] serum concentration of Lp(a) was 13.9 [7.5-24.6] mg/dL, with 151 patients (7.0%) above the recommended risk threshold of ≥ 50 mg/dL. Lp(a) levels increased with risk across all prevention groups. Being in the highest Lp(a) quintile (Q5) was associated with an increased frequency of ASCVD (28.9% versus 18.9% in the lowest quintile (Q1) for unstable angina; 18.7% versus 10.1% for myocardial infarction; 27.9% versus 17.0% for ischemic stroke). In the secondary prevention groups, the proportion of patients meeting an LDL-C target of ＜70 mg/dL decreased from 30.2% in Q1 to 19.0% in Q5 for Group II and from 32.9% to 16.3% for Group III. Despite a high prevalence of Lp(a) ≥ 50mg/dL in Japanese patients at high risk for ASCVD, it found that the Lp(a) testing rate was very low.

Impact of Remnant Cholesterol on Cardiovascular Risk in Diabetes.

Individuals with diabetes face increased risk of atherosclerotic cardiovascular disease (ASCVD), in part due to hyperlipidemia. Even after LDL cholesterol-lowering, residual ASCVD risk persists, part of which may be attributed to elevated remnant cholesterol. We describe the impact of elevated remnant cholesterol on ASCVD risk in diabetes. Preclinical, observational, and Mendelian randomization studies robustly suggest that elevated remnant cholesterol causally increases risk of ASCVD, suggesting remnant cholesterol could be a treatment target. However, the results of recent clinical trials of omega-3 fatty acids and fibrates, which lower levels of remnant cholesterol in individuals with diabetes, are conflicting in terms of ASCVD prevention. This is likely partly due to neutral effects of these drugs on the total level of apolipoprotein B(apoB)-containing lipoproteins. Elevated remnant cholesterol remains a likely cause of ASCVD in diabetes. Remnant cholesterol-lowering therapies should also lower apoB levels to reduce risk of ASCVD.

To Be or Not to Be: Elevated Troponin and the Role of Secondary Prevention of Atherosclerotic Cardiovascular Disease in ESKD

To Be or Not to Be: Elevated Troponin and the Role of Secondary Prevention of Atherosclerotic Cardiovascular Disease in ESKD

Non-oxidative modified low-density lipoproteins: The underappreciated risk factors for atherosclerosis.

Atherosclerosis, the pathological basis of most cardiovascular diseases, is a main risk factor causing about 20 million deaths each year worldwide. Oxidized low-density lipoprotein is recognized as the most important and independent risk factor in initiating and promoting atherosclerosis. Numerous antioxidants are extensively used in clinical practice, but they have no significant effect on reducing the morbidity and mortality of cardiovascular diseases. This finding suggests that researchers should pay more attention to the important role of non-oxidative modified low-density lipoprotein in atherosclerosis with a focus on oxidized low-density lipoprotein. This review briefly summarizes several important non-oxidative modified low-density lipoproteins associated with atherosclerosis, introduces the pathways through which these non-oxidative modified low-density lipoproteins induce the development of atherosclerosis in vivo, and discusses the mechanism of atherogenesis induced by these non-oxidative modified low-density lipoproteins. New therapeutic strategies and potential drug targets are provided for the prevention and treatment of atherosclerotic cardiovascular diseases.

Female participation, and sex-specific reporting practices, in polypill randomised controlled trials in the prevention of atherosclerotic cardiovascular disease: a secondary analysis of a systematic review

Abstract Background The polypill is an emerging strategy for the prevention and management of cardiovascular disease. We assessed the participation of females in randomised controlled trials evaluating polypills for prevention of cardiovascular disease and subsequent sex-specific analyses and reporting. Methods Cardiovascular polypill trials were identified through a systematic review. Data were extracted on the use of sex-specific eligibility criteria, female participation, and the conduct, findings, and interpretation of sex-specific analyses. Results Of 26 trials included, 12 (46%) excluded groups of females, mainly if pregnant or lactating or of childbearing potential. Female participation ranged from 10% to 73% across trials. Overall, 42% of included participants were female. Of 18 trials conducted in a mostly primary prevention population, females represented 49% of trial participants. In mixed or exclusively secondary prevention trials (n=8), females represented 26% of trial participants. Females represented 46% of trial participants in trials that excluded groups of females (n=12). In trials without explicit exclusion criteria (n=13), females represented 32% of trial participants. Nine out of 26 trials reported sex-stratified analyses (35% of trials; 70% of all participants). Of these, two found some evidence for possible sex differences, both reporting larger blood pressure effects in females than males. Four trials provided sex considerations in the discussion section of the report. Conclusion The participation of females in cardiovascular polypill trials is substantially higher in primary prevention trials as compared to trials conducted in mixed or exclusively secondary prevention populations. The use of sex-specific eligibility criteria was not linked to lower female participation. Sex-specific reporting is sparsely conducted, although most frequent in larger trials.

Interleukin-receptor antagonist and tumour necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases.

Interleukin-receptor antagonist and tumour necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases.

Impact of Guideline-Directed Statin Prescriptions on Cardiovascular Outcomes by Race in a Real-World Primary Prevention Cohort

BackgroundData on real-world statin prescription in large, private health care networks and impacts on primary prevention of atherosclerotic cardiovascular disease (ASCVD) outcomes across race are scarce. ObjectivesThe purpose of this study was to investigate the impact of statin prescription on ASCVD outcomes within and across race in a large, nongovernmental health care system. MethodsStatin prescription in Black and White patients without ASCVD was evaluated (2013-2019). Guideline-directed statin intensity was defined as at least “moderate” for intermediate and high-risk patients. Statin prescription at index and ASCVD outcomes at follow-up (myocardial infarction/revascularization, stroke, mortality) were assessed via electronic health care records using International Classification of Diseases-9 and 10 codes. Cox regression models, adjusted for CVD risk factors, were used to calculate HRs for association between statin prescription and incident ASCVD events across race. ResultsAmong 270,079 patients, 7.6% (n = 20,477) and 92.4% (n = 249,602) identified as Black and White, respectively. Significantly fewer Black patients were prescribed statin therapy than White patients (13.6% vs 19.0%; P < 0.001). At a mean follow-up of 6 years, patients with “no statin” prescription vs guideline-directed statin intensity showed increased ASCVD in Black patients (HR: 1.40 [95% CI: 1.05-1.86]), and White patients (HR: 1.32 [95% CI: 1.21-1.45]; P < 0.05) and all-cause mortality. Intermediate and high-risk Black patients faced a 17% higher risk of mortality compared to White patients. However, the interaction between race and statin prescription was not a significant predictor of incident ASCVD events. ConclusionsStatins remain underprescribed. Although Black patients received proportionally less statin prescription than White patients, this was not associated with higher risk of mortality in Black patients.

Sex specific analysis of patients with and without reported statin intolerance referred to a specialized outpatient lipid clinic

BackgroundLowering LDL-cholesterol is a fundamental goal for both primary and secondary prevention of atherosclerotic cardiovascular diseases. Our study aims to analyse potential sex disparities regarding the tolerability and effectiveness of lipid-lowering therapy in patients with and without reported statin intolerance who are being treated at a lipid-outpatient clinic.MethodsFrom 2017 to 2022, n = 1062 patients (n = 612 men, n = 450 women) at high-risk were referred to our lipid-outpatient clinic because of difficulties in lipid control by primary healthcare providers. The main therapeutic objective was to optimize lipid-lowering therapy according to current treatment guidelines.ResultsPatients presented with high LDL-C baseline levels (4.97 ± 1.81 mmol/l (192 ± 70 mg/dL) in men and 5.46 ± 2.04 mmol/l (211 ± 79 mg/dL) in women). Intolerance towards statins was reported more frequently by women (48.2%) than by men (38.9%, p = 0.004). LDL-C continuously decreased with individual treatment adjustments across follow-up visits. In total, treatment goals (LDL < 1.4 mmol/l (< 55 mg/dl) or < 1.8 mmol/l (< 70 mg/dl)) were accomplished in 75.8% of men and 55.5% of women after the last follow-up visit (p < 0.0001). In men, these data are almost identical in subjects with statin intolerance. In contrast, treatment goals were reached less frequently in women with statin intolerance compared to women tolerant to statin therapy.ConclusionEven if treated in a specialized lipid clinic, women are less likely to reach their target LDL-C than men, particularly when statin intolerant. Nevertheless, many patients with statin intolerance can be successfully treated using oral combination and PCSK9 inhibitor therapy. However, ongoing follow-up care to monitor progress and to adjust treatment plans is necessary to reach this goal.

Geriatric Pharmacotherapy Case Series: Clotting and Gender-Affirming Care.

Background A transfeminine patient is a 79-year-old with past medical history significant for type 2 diabetes mellitus, hypertension, gender dysphoria, chronic kidney disease, dyslipidemia, total left hip replacement, and recent provoked deep venous thromboembolism (DVT). She was seen by a pharmacist in a primary care clinic after her discharge from a skilled nursing facility. The patient was experiencing symptoms of gender dysphoria after discontinuation of her estradiol in setting of her DVT. Assessment Her renal function was calculated to ensure she was on appropriate dosing of her medications. Because her DVT was provoked, providers determined she would require only 3 months of anticoagulation. Her laboratory test results showed a subtherapeutic estradiol level and her estradiol was restarted. Additionally, aspirin was being prescribed for primary prevention of atherosclerotic cardiovascular disease and was discontinued. Outcome She has significant improvement in her gender dysphoria symptoms with resuming her estradiol and now has a therapeutic estradiol level. She is tolerating her direct oral coagulant well and reports good quality of life. Conclusion When reviewing medications for patients it is important to take several factors into account, including dose, appropriate indication, and patient preference. Pharmacists play a key role, through collaboration with providers, in assessing these medication-specific factors. Estradiol was stopped in this patient because of her DVT, but given her DVT was provoked after a recent surgery, it was unlikely that estradiol was the cause of her clot. Weighing the risks and benefits for any patient is important when determining what medications are appropriate to continue. Additionally, calculating renal function appropriately in a gender-non-conforming patients ensures appropriate and safe dosing.

Statin-associated muscle symptoms: A comprehensive exploration of epidemiology, pathophysiology, diagnosis, and clinical management strategies.

Statins are the first line of treatment for both primary and secondary prevention of atherosclerotic cardiovascular disease. Despite the positive effects of statins on cardiovascular events, not all patients can use them at an optimized dose. The reason for this is the skeletal muscle side effects, termed statin-associated muscle symptoms (SAMS). Despite extensive research, the precise pathophysiology of SAMS remains unclear and multiple mechanisms may contribute to this phenomenon. Various therapeutic options are available for the management of SAMS, ranging from rechallenging with the same or a different statin to utilizing non-statin therapeutic alternatives in patients intolerant to statins. However, the lack of consensus on the definition of SAMS, the absence of a definitive diagnostic test, and lack of a universally accepted management algorithm pose a great challenge in dealing with this entity. This review aims to explore the various pathophysiological mechanisms involved in SAMS and understand the difference between self-limited toxic myopathy and immune-mediated myopathy requiring immunomodulatory therapy. The conundrum of statin withdrawal, tapering, and rechallenge in SAMS will also be explored in detail along with the newer non-statin therapies that are available.

Comparison of Various Low Density Lipoprotein Cholesterol Calculators: Is It Time for the Friedewald Equation to Go in India?

Low-density lipoprotein cholesterol (LDL-c) is the main target in the management of dyslipidemia in primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Our study aims to compare the conventional and most popular Friedewald equation, and the more recent Sampson equation (literally unknown in India but more accurate), to the directly estimated LDL-c by the homogenous method. No such comparative study has been done in India. A multicenter retrospective analysis of the lipid profiles of patients whose LDL-c was derived directly by the homogenous method was included. Indirect LDL-c was estimated using the Friedewald and Sampson equations. The accuracy, error, and level of correlation between direct LDL-c and the two equations were assessed for concordance and discordance based on LDL-c categories (≤50, 51-70, 71-100, 101-130, ≥131 mg/dL). Upward discordance is when the calculated LDL-c was at least one category higher and downward discordance is when the calculated LDL-c was at least one category lower than the corresponding direct LDL-c (DLDL-c). Subgroup analyses were also done for triglycerides (TGLs) <150, 151-199, ≥200 mg/dL. TGL >400 were assessed separately. A total of 30,810 samples from four centers were studied. The overall mean DLDL-c was 107.86 mg/dL. The mean estimated LDL-c by Friedewald's equation (FLDL-c) and Sampson's equation (SLDL-c) were 101.37 and 104.37 mg/dL, respectively. There was statistical significance (p-value < 0.0005) in the mean difference when DLDL-c was compared with combined SLDL-c and FLDL-c as per the Games-Howell multiple comparison study, in which the mean difference was greater with the Friedewald equation (6.495) than with the Sampson equation (3.491). The overall concordance between FLDL-c vs DLDL-c and SLDL-c vs DLDL-c was nearly similar (74 vs 77%, respectively). The overall discordance upward was 5% with FLDL-c and 7% with SLDL-c (p-value < 0.0005). The overall discordance downward for FLDL-c and SLDL-c was 22 and 15% (p-value < 0.0005). When subgroup analysis was done for LDL-c ≤ 70, the downward discordance was 41% (FLDL-c) and 32% (SLDL-c), giving a false sense of goal LDL-c being achieved more often with FLDL-c. For LDL-c > 70, the corresponding downward discordance was 16 and 11%, respectively. Starting from TGL ≥ 200 mg/dL, there was consistent underestimation of LDL-c by the Friedewald equation. When TGL was > 400, the mean DLDL-c was 109 mg/dL, while for FLDL-c, it was 82 mg/dL and for SLDL-c, it was 98 mg/dL. Sampson's equation improves the accuracy of the indirectly calculated LDL-c compared to Friedewald's equation. The FLDL-c is estimated falsely low at LDL-c ≤ 70 mg/dL, giving a lower sense of LDL-c goal being achieved, and these patients will be undertreated. By switching to Sampson's equation, 9% in the LDL-c ≤ 70 mg/dL and 5% in the LDL-c > 70 mg/dL can be correctly classified. The shift to Sampson's equation requires a simple formula change and can be easily embraced in India-a small change but in the right direction.

2024 Guidelines of the Taiwan Society of Cardiology on the Primary Prevention of Atherosclerotic Cardiovascular Disease --- Part I.

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death worldwide and in Taiwan. It is highly prevalent and has a tremendous impact on global health. Therefore, the Taiwan Society of Cardiology developed these best-evidence preventive guidelines for decision-making in clinical practice involving aspects of primordial prevention including national policies, promotion of health education, primary prevention of clinical risk factors, and management and control of clinical risk factors. These guidelines cover the full spectrum of ASCVD, including chronic coronary syndrome, acute coronary syndrome, cerebrovascular disease, peripheral artery disease, and aortic aneurysm. In order to enhance medical education and health promotion not only for physicians but also for the general public, we propose a slogan (2H2L) for the primary prevention of ASCVD on the basis of the essential role of healthy dietary pattern and lifestyles: "Healthy Diet and Healthy Lifestyles to Help Your Life and Save Your Lives". We also propose an acronym of the modifiable risk factors/enhancers and relevant strategies to facilitate memory: " ABC2D2EFG-I'M2 ACE": Adiposity, Blood pressure, Cholesterol and Cigarette smoking, Diabetes mellitus and Dietary pattern, Exercise, Frailty, Gout/hyperuricemia, Inflammation/infection, Metabolic syndrome and Metabolic dysfunction-associated fatty liver disease, Atmosphere (environment), Chronic kidney disease, and Easy life (sleep well and no stress). Some imaging studies can be risk enhancers. Some risk factors/clinical conditions are deemed to be preventable, and healthy dietary pattern, physical activity, and body weight control remain the cornerstone of the preventive strategy.

When Does Primary Prevention Encroach on Secondary Prevention?

The risk of incident atherosclerotic cardiovascular disease (ASCVD) in primary prevention is typically lower than in secondary prevention. However, there is a spectrum of risk among individuals undergoing primary prevention with the risk in some individuals approaching those of secondary prevention. We review the clinical conditions wherein the risk in primary prevention is similar to that observed in secondary prevention. Among individuals without established ASCVD, coronary artery calcium (CAC) scores ≥ 300 AU are associated with ASCVD event rates similar to secondary prevention populations. CAC score ≥ 1,000 AU are associated with an ASCVD risk seen in very high-risk secondary prevention populations. Interpretation of these observations must however consider differences in the risk reduction strategies. Current guidelines dichotomize ASCVD prevention into primary and secondary prevention, but certain primary prevention patients have an ASCVD risk equivalent to that of secondary prevention populations. Identifying higher risk primary prevention populations will allow for better risk mitigation strategies.

Unidirectional association of clonal hematopoiesis with atherosclerosis development

Clonal hematopoiesis, a condition in which acquired somatic mutations in hematopoietic stem cells lead to the outgrowth of a mutant hematopoietic clone, is associated with a higher risk of hematological cancer and a growing list of nonhematological disorders, most notably atherosclerosis and associated cardiovascular disease. However, whether accelerated atherosclerosis is a cause or a consequence of clonal hematopoiesis remains a matter of debate. Some studies support a direct contribution of certain clonal hematopoiesis-related mutations to atherosclerosis via exacerbation of inflammatory responses, whereas others suggest that clonal hematopoiesis is a symptom rather than a cause of atherosclerosis, as atherosclerosis or related traits may accelerate the expansion of mutant hematopoietic clones. Here we combine high-sensitivity DNA sequencing in blood and noninvasive vascular imaging to investigate the interplay between clonal hematopoiesis and atherosclerosis in a longitudinal cohort of healthy middle-aged individuals. We found that the presence of a clonal hematopoiesis-related mutation confers an increased risk of developing de novo femoral atherosclerosis over a 6-year period, whereas neither the presence nor the extent of atherosclerosis affects mutant cell expansion during this timeframe. These findings indicate that clonal hematopoiesis unidirectionally promotes atherosclerosis, which should help translate the growing understanding of this condition into strategies for the prevention of atherosclerotic cardiovascular disease in individuals exhibiting clonal hematopoiesis.

Relationship of vegetarianism with body weight loss and ASCVD.

The association between a plant-based diet and weight loss and atherosclerotic cardiovascular disease (ASCVD) has not been fully elucidated. We performed a pooled analysis and Mendelian randomization (MR) analysis to investigate this question. We searched for randomized controlled trials on the effects of a plant-based diet on weight loss compared with a non-plant-based diet. In addition, a two-sample MR study was conducted. IVs were obtained from the genome-wide association studies (GWAS) on the exposures, and we obtained summary statistics on the outcomes. The inverse-variance weighted (IVW) method was used as the main analysis and other MR methods were performed as supplementary analyses. Individuals on the plant-based diet lost more weight than the non-plant-based diet group (WMD -0.96 kg; 95% CI: -1.32 to -0.60). Population conditions and energy restriction were identified as the study-level factors that influenced the pooling results in the subgroup analyses. Increased consumption of raw vegetables was significantly associated with lower BMI (IVW, β -0.35, 95% CI: -0.62 to -0.08, p = 0.012) and lower risk of obesity (IVW, OR 0.11, 95% CI: 0.01 to 0.99, p = 0.048), coronary heart disease (IVW, OR 0.44, 95% CI: 0.21 to 0.92, p = 0.029) and myocardial infarction (IVW, OR 0.39,95% CI: 0.15 to 0.98, p = 0.045) and a higher HDL-C (IVW, β 0.47, 95% CI: 0.24 to 0.70, p = 4×10-5). The present findings suggest that raw vegetable intake is beneficial for weight loss and prevention of ASCVD.