Cardiovascular Disease Risk Factors in Women: The Impact of Race and Ethnicity: A Scientific Statement From the American Heart Association.

Cardiovascular disease is the leading cause of death in women, yet differences exist among certain racial and ethnic groups. Aside from traditional risk factors, behavioral and environmental factors and social determinants of health affect cardiovascular health and risk in women. Language barriers, discrimination, acculturation, and health care access disproportionately affect women of underrepresented races and ethnicities. These factors result in a higher prevalence of cardiovascular disease and significant challenges in the diagnosis and treatment of cardiovascular conditions. Culturally sensitive, peer-led community and health care professional education is a necessary step in the prevention of cardiovascular disease. Equitable access to evidence-based cardiovascular preventive health care should be available for all women regardless of race and ethnicity; however, these guidelines are not equally incorporated into clinical practice. This scientific statement reviews the current evidence on racial and ethnic differences in cardiovascular risk factors and current cardiovascular preventive therapies for women in the United States.

Design and Rationale of the Social Determinants of the Risk of Hypertension in Women of Reproductive Age (SAFE HEART) Study: An American Heart Association Research Goes Red Initiative.

BACKGROUND: Cardiovascular health literacy (CVHL) and social determinants of health (SDoH) play interconnected and critical roles in shaping cardiovascular health (CVH) outcomes. However, awareness of CVH risk has declined markedly, from 65% of women being aware that cardiovascular disease (CVD) is the leading cause of death for women in 2009 to just 44% being aware in 2019. The American Heart Association Research Goes Red (RGR) initiative seeks to develop an open-source, longitudinal, dynamic registry that will help women to be aware of and participate in research studies, and to learn about CVD prevention. We proposed to leverage this platform, particularly among Black and Hispanic women of reproductive age, to address CVHL gaps and advance health equity. METHODS: The primary objective of the study is to evaluate the cross-sectional association of cardiovascular health literacy (CVHL), SDoH using a polysocial score, and CVH in women of reproductive age at increased risk of developing hypertension (HTN). To achieve this we will use a cross-sectional study design, that engages women already enrolled in the RGR registry (registry-enrolled). To enhance the racial and ethnic/social economic diversity of the cohort, we will additionally enroll 300 women from the Baltimore and Washington D.C. community into the Social Determinants of the Risk of Hypertension in Women of Reproductive Age (SAFE HEART) Study. Community-enrolled and registry-enrolled women will undergo baseline social phenotyping including detailed SDoH questionnaire, CVH metrics assessment, and CVHL assessment. The secondary objective is to assess whether a 4-month active health education intervention will result in a change in CVHL in the 300 community-enrolled women. DISCUSSION: The SAFE HEART study examines the association between CVHL, SDoH, and CVH, with a focus on racial and ethnic minority groups and socioeconomically disadvantaged women of reproductive age, and the ability to improve these parameters by an educational intervention. These findings will inform the future development of community-engaged strategies that address CVHL and SDoH among women of reproductive age.

Molecular Mechanisms of Vascular Health: Insights From Vascular Aging and Calcification.

Cardiovascular disease is the most common cause of death worldwide, especially beyond the age of 65 years, with the vast majority of morbidity and mortality due to myocardial infarction and stroke. Vascular pathology stems from a combination of genetic risk, environmental factors, and the biologic changes associated with aging. The pathogenesis underlying the development of vascular aging, and vascular calcification with aging, in particular, is still not fully understood. Accumulating data suggests that genetic risk, likely compounded by epigenetic modifications, environmental factors, including diabetes and chronic kidney disease, and the plasticity of vascular smooth muscle cells to acquire an osteogenic phenotype are major determinants of age-associated vascular calcification. Understanding the molecular mechanisms underlying genetic and modifiable risk factors in regulating age-associated vascular pathology may inspire strategies to promote healthy vascular aging. This article summarizes current knowledge of concepts and mechanisms of age-associated vascular disease, with an emphasis on vascular calcification.

Determinants of Incident Atherosclerotic Cardiovascular Disease Events Among Those With Absent Coronary Artery Calcium: Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The 2018 American Heart Association/American College of Cardiology/Multisociety cholesterol guideline states that statin therapy may be withheld or delayed among intermediate-risk individuals in the absence of coronary artery calcium (CAC=0). We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) events among individuals with CAC=0 over long-term follow-up. METHODS: We included participants with CAC=0 at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of clinical ASCVD at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors (cigarette smoking, diabetes, hypertension, preventive medication use [aspirin and statin], family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers) and adjudicated incident ASCVD outcomes. RESULTS: We studied 3416 individuals (mean [SD] age 58 [9] years; 63% were female, 33% White, 31% Black, 12% Chinese American, and 24% Hispanic). Over a median follow-up of 16 years, there were 189 ASCVD events (composite of coronary heart disease and stroke) of which 91 were coronary heart disease, 88 were stroke, and 10 were both coronary heart disease and stroke events. The unadjusted event rates of ASCVD were ≤5 per 1000 person-years among individuals with CAC=0 for most risk factors with the exception of current cigarette smoking (7.3), diabetes (8.9), hypertension (5.4), and chronic kidney disease (6.8). After multivariable adjustment, risk factors that were significantly associated with ASCVD included current cigarette smoking: hazard ratio, 2.12 (95% CI, 1.32-3.42); diabetes: hazard ratio, 1.68 (95% CI, 1.01-2.80); and hypertension: hazard ratio, 1.57 (95% CI, 1.06-2.33). CONCLUSIONS: Current cigarette smoking, diabetes, and hypertension are independently associated with incident ASCVD over a 16-year follow-up among those with CAC=0.

Noninvasive Plaque Imaging to Accelerate Coronary Artery Disease Drug Development.

Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque. Such distinct phenotypes reflect different pathophysiologic pathways and are associated with different risks for acute ischemic events. Noninvasive coronary imaging techniques, such as computed tomography, positron emission tomography, and coronary magnetic resonance imaging, have major potential to accelerate cardiovascular drug development, which has been affected by the high costs and protracted timelines of cardiovascular outcome trials. This may be achieved through enrichment of high-risk phenotypes with higher event rates or as primary end points of drug efficacy, at least in phase 2 trials, in a manner historically performed through intravascular coronary imaging studies. Herein, we provide a comprehensive review of the current technology available and its application in clinical trials, including implications for sample size requirements, as well as potential limitations. In its effort to accelerate drug development, the US Food and Drug Administration has approved surrogate end points for 120 conditions, but not for CAD. There are robust data showing the beneficial effects of drugs, including statins, on CAD progression and plaque stabilization in a manner that correlates with established clinical end points of mortality and major adverse cardiovascular events. This, together with a clear mechanistic rationale for using imaging as a surrogate CAD end point, makes it timely for CAD imaging end points to be considered. We discuss the importance of global consensus on these imaging end points and protocols and partnership with regulatory bodies to build a more informed, sustainable staged pathway for novel therapies.

Coronary artery calcium and sudden cardiac death: current evidence and future directions.

PURPOSE OF REVIEW: To provide a summary of the current evidence and highlight future directions regarding coronary artery calcium (CAC) and risk of sudden cardiac death (SCD). RECENT FINDINGS: Although up to 80% of all SCD is attributed to coronary heart disease (CHD), the subclinical atherosclerosis markers that help to improve SCD risk prediction are largely unknown. Recent observational data have demonstrated that, after adjustment for traditional risk factors, there is a stepwise higher risk for SCD across increasing CAC burden such that asymptomatic patients without overt atherosclerotic cardiovascular disease (ASCVD) experience a three-fold to five-fold higher SCD risk beginning at CAC at least 100 when compared with CAC = 0. Although the mechanisms underlying increasing CAC and SCD risk have yet to be fully elucidated, risk for myocardial infarction and scar, and/or exercise-induced ischemia may be potential mediators. SUMMARY: High CAC burden is an important risk factor for SCD in asymptomatic middle-aged adults, suggesting that SCD risk stratification can begin in the early stages of CHD via measurement of calcific plaque on noncontrast computed tomography. Despite the clinical inertia for downstream functional cardiac testing after detecting high CAC, comprehensive ASCVD prevention strategies should be the primary focus for SCD risk reduction.

Very High Coronary Artery Calcium (≥1000) and Association With Cardiovascular Disease Events, Non-Cardiovascular Disease Outcomes, and Mortality: Results From MESA.

BACKGROUND: There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations. METHODS: Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). RESULTS: Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm2), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups. CONCLUSIONS: Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.

Rationale and pathways forward in the implementation of coronary artery calcium-based enrichment of randomized trials.

The Food and Drug Administration recommends prognostic enrichment of randomized controlled trials (RCTs), aimed at restricting the study population to participants most likely to have events and therefore derive benefit from a given intervention. The coronary artery calcium (CAC) score is powerful discriminator of cardiovascular risk, and in this review we discuss how CAC may be used to augment widely used prognostic enrichment paradigms of RCTs of add-on therapies in primary prevention. We describe recent studies in this space, with special attention to the ability of CAC to further stratify risk among guideline-recommended candidates for add-on risk-reduction therapies. Given the potential benefits in terms of sample size, cost reduction, and overall RCT feasibility of a CAC-based enrichment strategy, we discuss approaches that may help maximize its advantages while minimizing logistical barriers and other challenges. Specifically, use of already existing CAC data to avoid the need to re-scan participants with previously documented high CAC scores, use of increasingly available, large clinical CAC databases to facilitate the identification of potential RCT participants, and implementation of machine learning approaches to measure CAC in existing computed tomography images performed for other purposes, will most likely boost the implementation of a CAC-based enrichment paradigm in future RCTs.

Diabetes Duration and Subclinical Myocardial Injury: The Atherosclerosis Risk in Communities Study (ARIC).

BACKGROUND: Diabetes exerts adverse effects on the heart, and a longer diabetes duration is associated with greater heart failure risk. We studied diabetes duration and subclinical myocardial injury, as reflected by high-sensitivity cardiac troponin (hs-cTnT). METHODS: We analyzed 9052 participants without heart failure or coronary heart disease (mean age 63 years, 58% female, 21% Black, 15% with diabetes) at The Atherosclerosis Risk in Communities Study (ARIC) Visit 4 (1996 to 1998). Diabetes duration was calculated based on diabetes status at Visits 1 (1987 to 1989) through 4, or using self-reported age of diabetes diagnosis prior to Visit 1. We used multinomial logistic regression to determine the association of diabetes duration with increased (≥14 ng/L) or detectable (≥6 ng/L) Visit 4 hs-cTnT, relative to undetectable hs-cTnT, adjusted for demographics and cardiovascular risk factors. RESULTS: The prevalence of increased Visit 4 hs-cTnT was higher in persons with longer diabetes duration, from 12% for those with diabetes 0 to <5 years up to 31% among those with diabetes for ≥15 years (P for trend <0.0001). New onset diabetes at Visit 4 was associated with 1.92× higher relative risk (95% CI, 1.27-2.91) of increased hs-cTnT than no diabetes. Longer diabetes duration was associated with greater myocardial injury, with duration ≥15 years associated with 9.29× higher risk (95% CI, 5.65-15.29) for increased hs-cTnT and 2.07× (95% CI, 1.24-3.16) for detectable hs-cTnT, compared to no diabetes. CONCLUSIONS: Longer diabetes duration is strongly associated with subclinical myocardial injury. Interventional studies are needed to assess whether the prevention and delay of diabetes onset can mitigate early myocardial damage.

Controversies in the Use of Omega-3 Fatty Acids to Prevent Atherosclerosis.

PURPOSE OF REVIEW: We discuss current controversies in the clinical use of omega-3 fatty acids (FA), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and examine discrepancies between recent trials. Furthermore, we discuss potential side effects reported in these studies and the role of mixed omega-3 FA dietary supplements and concerns about their use. RECENT FINDINGS: REDUCE-IT showed that addition of icosapent ethyl, a highly purified form of EPA, can reduce risk of cardiovascular events among statin-treated individuals with high triglycerides. Additional supportive evidence for EPA has come from other trials and meta-analyses of omega-3 FA therapy. In contrast, trials of mixed EPA/DHA products have consistently failed to improve cardiovascular outcomes. Discrepancies in results reported in RCTs could be explained by differences in omega-3 FA products, dosing, study populations, and study designs including the placebo control formulation. Evidence obtained from highly purified forms should not be extrapolated to other mixed formulations, including "over-the-counter" omega-3 supplements. Targeting TG-rich lipoproteins represents a new frontier for mitigating ASCVD risk. Clinical and basic research evidence suggests that the use of omega-3 FA, specifically EPA, appears to slow atherosclerosis by reducing triglyceride-rich lipoproteins and/or inflammation, therefore addressing residual risk of clinical ASCVD.

Cardio-Obstetrics: the Next Frontier in Cardiovascular Disease Prevention.

PURPOSE OF REVIEW: Internationally, cardiovascular disease (CVD) is the leading cause of death in women. With risk factors for CVD continuing to rise, early identification and management of chronic diseases such as hypertension, diabetes, and obstructive sleep apnea is necessary for prevention. Pregnancy is a natural stress test for women with risk factors who may be predisposed to CVD and offers a unique opportunity to not only recognize disease but also implement effective and long-lasting strategies for prevention. RECENT FINDINGS: Prevention begins before pregnancy, as preconception screening, counseling, and optimization of chronic diseases can improve maternal and fetal outcomes. Throughout pregnancy, women should maintain close follow-up, continued reevaluation of risk factors, with counseling when necessary. Continued healthcare engagement during the "fourth trimester," 3 months following delivery, allows clinicians to continue monitoring the evolution of chronic diseases, encourage ongoing lifestyle counseling, and connect women with primary care and appropriate specialists if needed. Unfortunately, this postpartum period represents a major care gap, as a significant proportion of most women do not attend their scheduled visits. Social determinants of health including decreased access to care and economic instability lead to increased risk factors throughout pregnancy but particularly play a role in poor compliance with postpartum follow-up. The use of telemedicine clinics and remote monitoring may prove to be effective interventions, bridging the gap between physicians and patients and improving follow-up for at-risk women. While many clinicians are beginning to understand the impact of CVD on women, screening and prevention strategies are not often implemented until much later in life. Pregnancy creates an opportunity to begin engaging women in cardiovascular protective strategies before the development of the disease.

THE ABCDE'S OF PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE.

The growing burden of obesity, smoking, elevated cholesterol, diabetes, hypertension, sedentary lifestyle, and unhealthy dietary habits fuels cardiovascular disease. In 2015, the rates of cardiovascular disease in the United States rose for the first time after decades of steady decline. To combat this rising trend, there is a great need to emphasize primary cardiovascular prevention. In this review, we provide a summary of the current primary prevention recommendations using a simplified ABCDE approach. The aim is to help clinicians utilize an easy-to-use, structured approach to primary atherosclerotic cardiovascular disease prevention.

How low is safe? The frontier of very low (<30 mg/dL) LDL cholesterol.

Low-density lipoprotein cholesterol (LDL-C) is a proven causative factor for developing atherosclerotic cardiovascular disease. Individuals with genetic conditions associated with lifelong very low LDL-C levels can be healthy. We now possess the pharmacological armamentarium (statins, ezetimibe, PCSK9 inhibitors) to reduce LDL-C to an unprecedented extent. Increasing numbers of patients are expected to achieve very low (<30 mg/dL) LDL-C. Cardiovascular event reduction increases log linearly in association with lowering LDL-C, without reaching any clear plateau even when very low LDL-C levels are achieved. It is still controversial whether lower LDL-C levels are associated with significant clinical adverse effects (e.g. new-onset diabetes mellitus or possibly haemorrhagic stroke) and long-term data are needed to address safety concerns. This review presents the familial conditions characterized by very low LDL-C, analyses trials with lipid-lowering agents where patients attained very low LDL-C, and summarizes the benefits and potential adverse effects associated with achieving very low LDL-C. Given the potential for cardiovascular benefit and short-term safe profile of very low LDL-C, it may be advantageous to attain such low levels in specific high-risk populations. Further studies are needed to compare the net clinical benefit of non-LDL-C-lowering interventions with very low LDL-C approaches, in addition to comparing the efficacy and safety of very low LDL-C levels vs. current recommended targets.

A cohort study and meta-analysis of isolated diastolic hypertension: searching for a threshold to guide treatment.

AIMS: Whether isolated diastolic hypertension (IDH), as defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline, is associated with cardiovascular disease (CVD) has been disputed. We aimed to further study the associations of IDH with (i) subclinical CVD in the form of coronary artery calcium (CAC), (ii) incident systolic hypertension, and (iii) CVD events. METHODS AND RESULTS: We used multivariable-adjusted logistic and Cox regression to test whether IDH by 2017 ACC/AHA criteria (i.e. systolic blood pressure <130 mmHg and diastolic blood pressure ≥80 mmHg) was associated with the above outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA). In a random-effects meta-analysis of the association between IDH and CVD events, we combined the MESA results with those from seven other previously published cohort studies. Among the 5104 MESA participants studied, 7.5% had IDH by the 2017 ACC/AHA criteria. There was no association between IDH and CAC [e.g. adjusted prevalence odds ratio for CAC >0 of 0.88 (95% CI 0.66, 1.17)]. Similarly, while IDH was associated with incident systolic hypertension, there was no statistically significant associations with incident CVD [hazard ratio 1.19 (95% CI 0.77, 1.84)] or death [hazard ratio 0.94 (95% CI 0.65, 1.36)] over 13 years in MESA. In a stratified meta-analysis of eight cohort studies (10 037 843 participants), the 2017 IDH definition was also not consistently associated with CVD and the relative magnitude of any potential association was noted to be numerically small [e.g. depending on inclusion criteria applied in the stratification, the adjusted hazard ratios ranged from 1.04 (95% CI 0.98, 1.10) to 1.09 (95% 1.03, 1.15)]. CONCLUSION: The lack of consistent excess in CAC or CVD suggests that emphasis on healthy lifestyle rather than drug therapy is sufficient among the millions of middle-aged or older adults who now meet the 2017 ACC/AHA criteria for IDH, though they require follow-up for incident systolic hypertension. These findings may not extrapolate to adults younger than 40 years, motivating further study in this age group.

Lifelong Aspirin for All in the Secondary Prevention of Chronic Coronary Syndrome: Still Sacrosanct or Is Reappraisal Warranted?

Four decades have passed since the first trial suggesting the efficacy of aspirin in the secondary prevention of myocardial infarction. Further trials, collectively summarized by the Antithrombotic Trialists' Collaboration, solidified the historical role of aspirin in secondary prevention. Although the benefit of aspirin in the immediate phase after a myocardial infarction remains incontrovertible, a number of emerging lines of evidence, discussed in this narrative review, raise some uncertainty as to the primacy of aspirin for the lifelong management of all patients with chronic coronary syndrome (CCS). For example, data challenging the previously unquestioned role of aspirin in CCS have come from recent trials where aspirin was discontinued in specific clinical scenarios, including early discontinuation of the aspirin component of dual antiplatelet therapy after percutaneous coronary intervention and the withholding of aspirin among patients with both CCS and atrial fibrillation who require anticoagulation. Recent primary prevention trials have also failed to consistently demonstrate net benefit for aspirin in patients treated to optimal contemporary cardiovascular risk factor targets, indicating that the efficacy of aspirin for secondary prevention of CCS may similarly have changed with the addition of more modern secondary prevention therapies. The totality of recent evidence supports further study of the universal need for lifelong aspirin in secondary prevention for all adults with CCS, particularly in stable older patients who are at highest risk for aspirin-induced bleeding.

Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019: The MESA Study (Multi-Ethnic Study of Atherosclerosis).

BACKGROUND: Recent American College of Cardiology/American Heart Association Primary Prevention Guidelines recommended considering low-dose aspirin therapy only among adults 40 to 70 years of age who are at higher atherosclerotic cardiovascular disease (ASCVD) risk but not at high risk of bleeding. However, it remains unclear how these patients are best identified. The present study aimed to assess the value of coronary artery calcium (CAC) for guiding aspirin allocation for primary prevention by using 2019 aspirin meta-analysis data on cardiovascular disease relative risk reduction and bleeding risk. METHODS: The study included 6470 participants from the MESA Study (Multi-Ethnic Study of Atherosclerosis). ASCVD risk was estimated using the pooled cohort equations, and 3 strata were defined: <5%, 5% to 20%, and >20%. All participants underwent CAC scoring at baseline, and CAC scores were stratified as =0, 1 to 99, ≥100, and ≥400. A 12% relative risk reduction in cardiovascular disease events was used for the 5-year number needed to treat (NNT5) calculations, and a 42% relative risk increase in major bleeding events was used for the 5-year number needed to harm (NNH5) estimations. RESULTS: Only 5% of MESA participants would qualify for aspirin consideration for primary prevention according to the American College of Cardiology/American Heart Association guidelines and using >20% estimated ASCVD risk to define higher risk. Benefit/harm calculations were restricted to aspirin-naive participants <70 years of age not at high risk of bleeding (n=3540). The overall NNT5 with aspirin to prevent 1 cardiovascular disease event was 476 and the NNH5 was 355. The NNT5 was also greater than or similar to the NNH5 among estimated ASCVD risk strata. Conversely, CAC≥100 and CAC≥400 identified subgroups in which NNT5 was lower than NNH5. This was true both overall (for CAC≥100, NNT5=140 versus NNH5=518) and within ASCVD risk strata. Also, CAC=0 identified subgroups in which the NNT5 was much higher than the NNH5 (overall, NNT5=1190 versus NNH5=567). CONCLUSIONS: CAC may be superior to the pooled cohort equations to inform the allocation of aspirin in primary prevention. Implementation of current 2019 American College of Cardiology/American Heart Association guideline recommendations together with the use of CAC for further risk assessment may result in a more personalized, safer allocation of aspirin in primary prevention. Confirmation of these findings in experimental settings is needed.

Reducing disparities in adverse pregnancy outcomes in the United States.

There is growing evidence that rural and racial disparities and social determinants of health (SDOH) impact adverse pregnancy outcomes (APOs) and overall maternal mortality in the United States. These APOs, such as preeclampsia, preterm birth, and intrauterine growth restriction, are in-turn associated with increased risk of future cardiovascular disease (CVD) later in life. Importantly, SDOH such as socioeconomic disadvantages, poor health literacy, transportation barriers, lack of access to adequate health care, food insecurity, and psychosocial stressors have cascading effects on APOs and downstream cardiovascular health. These SDOH are also deeply intertwined with and compounded by existing racial and rural disparities. Pregnancy thus provides a unique opportunity to identify at-risk women from a social determinants perspective, and provide early interventions to optimize long-term CVD and mitigate cardiovascular health disparities. Addressing the challenges posed by these disparities requires a multi-pronged approach and involves national, regional, and individual level solutions. Eliminating disparities will necessitate a nationwide obligation to ensure health care equity via enhanced health insurance coverage, resource investment, and public and clinician accountability.

Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Special Report From the American Heart Association and American College of Cardiology.

Risk assessment is a critical step in the current approach to primary prevention of atherosclerotic cardiovascular disease. Knowledge of the 10-year risk for atherosclerotic cardiovascular disease identifies patients in higher-risk groups who are likely to have greater net benefit and lower number needed to treat for both statins and antihypertensive therapy. Current US prevention guidelines for blood pressure and cholesterol management recommend use of the pooled cohort equations to start a process of shared decision-making between clinicians and patients in primary prevention. The pooled cohort equations have been widely validated and are broadly useful for the general US clinical population. But, they may systematically underestimate risk in patients from certain racial/ethnic groups, those with lower socioeconomic status or with chronic inflammatory diseases, and overestimate risk in patients with higher socioeconomic status or who have been closely engaged with preventive healthcare services. If uncertainty remains for patients at borderline or intermediate risk, or if the patient is undecided after a patient-clinician discussion with consideration of risk enhancing factors (eg, family history), additional testing with measurement of coronary artery calcium can be useful to reclassify risk estimates and improve selection of patients for use or avoidance of statin therapy. This special report summarizes the rationale and evidence base for quantitative risk assessment, reviews strengths and limitations of existing risk scores, discusses approaches for refining individual risk estimates for patients, and provides practical advice regarding implementation of risk assessment and decision-making strategies in clinical practice.

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

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.

2019 clinical trials in lipid lowering.

PURPOSE OF REVIEW: Lipid-lowering therapies play a major role in reducing atherosclerotic cardiovascular disease (ASCVD). This article reviews the most recent lipid-lowering therapy trials, many of which provide a unique opportunity to further reduce low-density lipoprotein cholesterol (LDL-C) levels and ASCVD risk on top of statin therapy, and in doing so further decrease the number of future major adverse cardiovascular events. RECENT FINDINGS: Although statin therapy has been the mainstay of treatment for lowering LDL-C levels for many years, many individuals require additional or alternative options for further reducing their risk. Trials on previously studied therapies, such as PCSK9 inhibitors, and new therapies, including inclisiran, bempedoic acid and icosapent ethyl demonstrate significant potential for further lowering of LDL-C levels and risk for events on top of maximally tolerated statin therapy with favourable side effect profiles. SUMMARY: As therapies for ASCVD prevention continue to emerge, clinicians will need to identify the appropriate treatment for individuals based on their estimated risk and risk-enhancing factors. When statin therapy is either not sufficient or patients do not tolerate adequate statin therapy, relying on newer therapies, such as PCSK9-inhibitors, inclisiran, bempedoic acid and icosapent ethyl, will be critical to maximize risk factor profiles to reduce adverse outcomes.