Understanding the spectrum of cardiovascular risk in women - A primer for prevention.

Cardiovascular disease (CVD) is the leading cause of death in women worldwide and the lifetime risk of CVD in women is similar to men. However, the pathophysiology of CVD varies between women and men necessitating a sex-specific understanding of cardiovascular (CV) risk. A belief that women have a lower CVD risk than men, and an underrepresentation in clinical research for many years has led to a paucity of evidence in the prevention and management of CVD in women. Many recent efforts have tried to bridge the gap. As a result, we now know that traditional risk factors impact CVD risk differently in women when compared with men. There are also numerous sex-specific and pregnancy related risk factors that modify the risk and can predict the future development of CVD in women. This is important as risk calculators, in general, tend to misclassify risk in young women with nontraditional CVD risk factors. To address this, guidelines have introduced the concept of risk enhancers that can suggest a higher risk. The use of coronary artery calcium score can further accurately delineate risk in these women, leading to an appropriate matching of therapy to underlying risk. This review discusses implementation strategies that are essential to mitigate disparities in CVD outcomes and optimizing CVD risk in women.

The utility of coronary artery calcium scoring to enhance cardiovascular risk assessment for South Asian adults.

South Asian individuals represent a highly diverse population and are one of the fastest growing ethnic groups in the United States. This population has a high prevalence of traditional and non-traditional cardiovascular disease (CVD) risk factors and a disproportionately high prevalence of coronary heart disease. To reflect this, current national society guidelines have designated South Asian ancestry as a "risk enhancing factor" which may be used to guide initiation or intensification of statin therapy. However, current methods of assessing cardiovascular risk in South Asian adults may not adequately capture the true risk in this diverse population. Coronary artery calcium (CAC) scoring provides a reliable, reproducible, and highly personalized method to provide CVD risk assessment and inform subsequent pharmacotherapy recommendations, if indicated. This review describes the utility of CAC scoring for South Asian individuals.

Association of cardiovascular health with subclinical coronary atherosclerosis progression among five racial and ethnic groups: The MASALA and MESA studies.

BACKGROUND AND AIMS: South Asian adults (SA) are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared with other racial/ethnic groups. Life's Simple 7 (LS7) is a guideline-recommended, cardiovascular health (CVH) construct to guide optimization of cardiovascular risk factors. We sought to assess if the LS7 metrics predict coronary artery calcium (CAC) incidence and progression in asymptomatic SA compared with four other racial/ethnic groups. METHODS: We assessed the distribution of CVH metrics (inadequate: score 0-8, average: 9-10, optimal: 11-14, and per 1-unit higher score) and its association with incidence and progression of CAC among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study compared with other race/ethnic groups from the Multiethnic Study of Atherosclerosis (MESA). RESULTS: We included 810 SA, 2622 Non-Hispanic White (NHW), and 4192 Other adults (collectively 1893 Black, 1496 Hispanic and 803 Chinese American participants, respectively). SA and White participants compared to Other race/ethnicity groups were more likely to have optimal CVH metrics (26% SA vs 28% White participants vs 21% Other, respectively, p < 0.001). Similar to NHW and the Other race/ethnic group, SA participants with optimal baseline CVH were less likely to develop incident CAC on follow-up evaluation compared to participants with inadequate CVH metrics, optimal CVH/CAC = 0: 24% SA, 28% NHW, and 15% Other (p < 0.01). In multivariable linear and logistic regression models, there was no difference in annualized CAC incidence or progression between each race/ethnic group (pinteraction = 0.85 and pinteraction = 0.17, respectively). Optimal blood pressure control was associated with lower CAC incidence among SA participants [OR (95% CI): 0.30 (0.14-0.63), p < 0.01] and Other race and ethnicity participants [0.32 (0.19-0.53), p < 0.01]. CONCLUSIONS: Optimal CVH metrics are associated with lower incident CAC and CAC progression among South Asians, similar to other racial groups/ethnicities. These findings underscore the importance of optimizing and maintaining CVH to mitigate the future risk of subclinical atherosclerosis in this higher risk population.

Epidemiology and Prognostic Implications of Coronary Artery Calcium in Asymptomatic Individuals With Prediabetes: A Multicohort Study.

OBJECTIVE: To describe the epidemiology and prognostic value of coronary artery calcium (CAC) in individuals with prediabetes. RESEARCH DESIGN AND METHODS: We pooled participants free of clinical atherosclerotic cardiovascular disease (ASCVD) from four prospective cohorts: the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. Two definitions were used for prediabetes: inclusive (fasting plasma glucose [FPG] ≥100 to <126 mg/dL and hemoglobin A1c [HbA1c] ≥5.7% to <6.5%, if available, and no glucose-lowering medications) and restrictive (FPG ≥110 to <126 mg/dL and HbA1c ≥5.7% to <6.5%, if available, among participants not taking glucose-lowering medications). RESULTS: The study included 13,376 participants (mean age 58 years; 54% women; 57% White; 27% Black). The proportions with CAC ≥100 were 17%, 22%, and 37% in those with euglycemia, prediabetes, and diabetes, respectively. Over a median (25th-75th percentile) follow-up time of 14.6 (interquartile range 7.8-16.4) years, individuals with prediabetes and CAC ≥100 had a higher unadjusted 10-year incidence of ASCVD (13.4%) than the overall group of those with diabetes (10.6%). In adjusted analyses, using the inclusive definition of prediabetes, compared with euglycemia, the hazard ratios (HRs) for ASCVD were 0.79 (95% CI 0.62, 1.01) for prediabetes and CAC 0, 0.70 (0.54, 0.89) for prediabetes and CAC 1-99, 1.54 (1.27, 1.88) for prediabetes and CAC ≥100, and 1.64 (1.39, 1.93) for diabetes. Using the restrictive definition, the HR for ASCVD was 1.63 (1.29, 2.06) for prediabetes and CAC ≥100. CONCLUSIONS: CAC ≥100 is frequent among individuals with prediabetes and identifies a high ASCVD risk subgroup in which the adjusted ASCVD risk is similar to that in individuals with diabetes.

Identification and Management of Atherosclerotic Cardiovascular Disease Risk in South Asian Populations in the U.S.

South Asians (SAs, individuals with ancestry from Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka) are among the fastest growing ethnic subgroups in the United States. SAs typically experience a high prevalence of diabetes, abdominal obesity, and hypertension, among other cardiovascular disease risk factors, which are often under recognized and undermanaged. The excess coronary heart disease risk in this growing population must be critically assessed and managed with culturally appropriate preventive services. Accordingly, this scientific document prepared by a multidisciplinary group of clinicians and investigators in cardiology, internal medicine, pharmacy, and SA-centric researchers describes key characteristics of traditional and nontraditional cardiovascular disease risk factors, compares and contrasts available risk assessment tools, discusses the role of blood-based biomarkers and coronary artery calcium to enhance risk assessment and prevention strategies, and provides evidenced-based approaches and interventions that may reduce coronary heart disease disparities in this higher-risk population.

Implementation of Prevention Science to Eliminate Health Care Inequities in Achieving Cardiovascular Health: A Scientific Statement From the American Heart Association.

Prevention of cardiovascular and related diseases is foundational to attaining ideal cardiovascular health to improve the overall health and well-being of individuals and communities. Social determinants of health and health care inequities adversely affect ideal cardiovascular health and prevention of disease. Achieving optimal cardiovascular health in an effective and equitable manner requires a coordinated multidisciplinary and multilayered approach. In this scientific statement, we examine barriers to ideal cardiovascular health and its related conditions in the context of leveraging existing resources to reduce health care inequities and to optimize the delivery of preventive cardiovascular care. We systematically discuss (1) interventions across health care environments involving direct patient care, (2) leveraging health care technology, (3) optimizing multispecialty/multiprofession collaborations and interventions, (4) engaging local communities, and (5) improving the community environment through health-related government policies, all with a focus on making ideal cardiovascular health equitable for all individuals.

Clinical programs for cardiometabolic health for South Asian patients in the United States: A review of key program components.

Medical literature shows that South Asians have approximately a 2-fold higher risk of atherosclerotic cardiovascular disease (CVD) compared with other populations. Given this high prevalence, clinical programs to promote cardiovascular health have emerged in the United States that are dedicated to clinical care for South Asian individuals. In this review, we have summarized the key characteristics of clinical programs in the U.S. dedicated to preventing and managing CVD in South Asian American patients. These clinical centers have many unique components in common that are catered to South Asian patient populations including ethnicity concordance of clinical providers, intensive cardiovascular screening protocols with laboratory studies and potentially genetic testing, dieticians and nutritionists who are familiar with South Asian-style dietary patterns, health coaches to support behavior change, community outreach programs, and involvement in clinical research to learn further about risk factors, prevention, and treatment of cardiovascular disease in South Asian populations. There are still many evidence and programmatic gaps left to uncover in the prevention, diagnosis, and management of CVD in South Asian. This review provides guidance for important features, barriers, and facilitators for future cardiovascular centers to develop in the United States where they can serve South Asian populations.

Coronary Artery Calcium Dispersion and Cause-Specific Mortality.

Coronary artery calcium (CAC) measures subclinical atherosclerosis and improves risk stratification. CAC characteristics-including vessel(s) involved, number of vessels, volume, and density-have been shown to differentially impact risk. We assessed how dispersion-either the number of calcified vessels or CAC phenotype (diffuse, normal, and concentrated)-impacted cause-specific mortality. The CAC Consortium is a retrospective cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC scoring. This study included patients with CAC >0 (n = 28,147). CAC area, CAC density, and CAC phenotypes (derived from the index of diffusion = 1 - [CAC in most concentrated vessel/total Agatston score]) were calculated. The associations between CAC characteristics and cause-specific mortality were assessed. The participant details included (n = 28,147): mean age 58.3 years, 25% female, 89.6% White, and 66% had 2+ calcified vessels. Diabetes, hypertension, and hyperlipidemia were predictors of multivessel involvement (p <0.001). After controlling for the overall CAC score, those with 4-vessel CAC involvement had more CAC area and less dense calcifications than those with 1-vessel. There was a graded increase in all-cause and cardiovascular disease (CVD)- and CHD-specific mortality as the number of calcified vessels increased. Among those with ≥2 vessels involved (n = 18,516), a diffuse phenotype was associated with a higher CVD-specific mortality and had a trend toward higher all-cause and CHD-specific mortality than a concentrated CAC phenotype. Diffuse CAC involvement was characterized by less dense calcification, more CAC area, multiple coronary vessel involvement, and presence of certain traditional risk factors. There is a graded increase in all-cause and CVD- and CHD-specific mortality with increasing CAC dispersion.

Leveling the playing field: The utility of coronary artery calcium scoring in cardiovascular risk stratification in South Asians.

South Asian (SA) individuals, particularly those that reside in the United States and other Westernized countries, are at an elevated risk for ASCVD and mortality related to ASCVD. The 2018 ACC/AHA/Multi-society Cholesterol guideline listed SA as a high-risk ethnicity, underscoring the importance of treating modifiable risk factors to reduce ASCVD burden. Coronary artery calcium (CAC), a highly specific marker of subclinical atherosclerosis, may be a useful test to improve risk stratification among SA individuals. CAC testing is a cost-effective, highly reproducible, and specific marker of subclinical atherosclerosis, shown to improve ASCVD risk assessment across all racial/ethnic groups, thereby serving as a guide for initiating or deferring preventive therapies. In this White Paper we will discuss the use of CAC scoring to optimize risk stratification and delivery of preventive therapies to individuals of SA ethnicity.

Association of Coronary Artery Calcium Density and Volume With Predicted Atherosclerotic Cardiovascular Disease Risk and Cardiometabolic Risk Factors in South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study.

Individuals of South Asian (SA) ancestry are predisposed to a higher risk of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC) volume and density can identify coronary plaque characteristics unique to SA that may provide important prognostic information to identify high risk individuals beyond traditional CAC scores. We used data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA). CAC density and volume were assessed according to established protocols. ASCVD risk was estimated using the pooled cohort equations (PCE). Multivariable-adjusted linear regression models were used to study the association between the PCE and advanced CAC measures, and between cardiovascular risk factors and CAC density and volume. Our analyses included 1,155 participants (mean age 57 (SD 9) years, 52% men) with information on advanced CAC measures. After multivariable-adjustment, the PCE was associated with both CAC density (ß 0.24, 95% CI 0.12,0.35) and CAC volume (ß 0.43, 95% CI 0.38,0.48). High-density lipoprotein cholesterol was directly associated with CAC density while waist circumference was inversely associated with it. Body mass index, hypertension status, statin use, diabetes, and HOMA-IR were all directly associated with CAC volume. Estimated ASCVD risk was associated with both CAC volume and density. Different cardiometabolic risk factors are associated with CAC density and volume. Future longitudinal studies are required to demonstrate the interrelationship of advanced CAC measures and cardiovascular risk factors with incident ASCVD outcomes.

Cardiovascular Risk Management in the South Asian Patient: A Review.

South Asians represent a growing percentage of the diverse population in the U.S. and are disproportionately impacted by a greater burden of aggressive and premature cardiovascular disease. There are multiple potential explanations for these findings including a high prevalence of traditional risk factors (particularly diabetes, dyslipidemia, and obesity), a genetic predisposition, and unique lifestyle factors. In this review, we discuss the cardiovascular risk stratification and disease management goals for South Asian adults. We review the pharmacologic and non-pharmacologic interventions studied in this population and discuss the role of specialized clinics and digital outreach to improve care for this vulnerable group of patients.

New Strategies for Lowering Low Density Lipoprotein Cholesterol for Cardiovascular Disease Prevention.

Purpose of review: The primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on optimizing cardiovascular health and appropriate pharmacotherapy, a mainstay of which is low-density lipoprotein-cholesterol (LDL-C) lowering. Typically, statin therapy remains the first line approach. Advances in technology and understanding of lipid metabolism have facilitated the development of several novel therapeutic targets and medications within the last decade. This review focuses on medications recently approved by the U.S. Food and Drug Administration (FDA) for the reduction of LDL-C and ASCVD risk, as well as new therapies in the pipeline. Recent findings: Novel lipid therapies aim to lower risk of ASCVD by targeting reduction of atherogenic compounds, such as LDL, lipoprotein(a) (Lp(a)), and triglyceride-rich lipoproteins. Evolocumab and alirocumab, monoclonal antibody proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors which lower LDL-C by approximately 60%, have emerged as important therapies for use in patients with ASCVD as well as familial hypercholesterolemia (FH). Bempedoic acid, an ATP citrate lyase inhibitor, is an oral medication recently approved that can lower LDL-C by approximately 18% alone and 38% when combined with ezetimibe. Inclisiran, a small-interfering RNA (siRNA) molecule which inhibits the translation of PCSK9, is the most recently FDA-approved LDL-C lowering medication, and can reduce LDL-C by approximately 50% with twice yearly subcutaneous dosing. The cardiovascular outcome trials for bempedoic acid and inclisiran are still on-going. Evinacumab, a monoclonal antibody which targets angiopoietin-like protein 3 (ANGPTL3), has been approved for use in patients with homozygous FH. SiRNAs and anti-sense oligonucleotides (ASO) facilitating selective inhibition of the production of targeted proteins including Lp(a) and ANGLPTL3 are active areas of clinical investigation. Summary: Recently several novel LDL-C lowering medications have been approved. New therapeutic targets have been identified and present additional means of lowering LDL-C and other atherogenic compounds for patients who remain at high ASCVD risk.

South Asian ethnicity: What can we do to make this risk enhancer a risk equivalent?

South Asians account for around 25% of the global population and are the fastest-growing ethnicity in the US. This population has an increasing burden of atherosclerotic cardiovascular disease (ASCVD) which is also seen in the diaspora. Current risk prediction equations underestimate this risk and consider the South Asian ethnicity as a risk-enhancer among those with borderline-intermediate risk. In this review, we discuss why the South Asian population is at a higher risk of ASCVD and strategies to mitigate this increased risk.

Healthcare Access Among Individuals of Asian Descent in the U.S.

Introduction: Some groups of Asian Americans, especially Asian Indians, experience higher rates of atherosclerotic cardiovascular disease (ASCVD) compared with other groups in the U.S. Barriers in accessing medical care partly may explain this higher risk as a result of delayed screening for cardiovascular risk factors and timely initiation of preventive treatment. Methods: Cross-sectional data were utilized from the 2006 to 2015 National Health Interview Survey (NHIS). Barriers to accessing medical care included no place to seek medical care when needed, no healthcare coverage, no care due to cost, delayed care due to cost, inability to afford medication, or not seeing a doctor in the past 12 months. Results: The study sample consisted of 18,150 Asian individuals, of whom 20.5% were Asian Indian, 20.5% were Chinese, 23.4% were Filipino, and 35.6% were classified as "Other Asians". The mean (standard error) age was 43.8 (0.21) years and 53% were women. Among participants with history of hypertension, diabetes mellitus, or ASCVD (prevalence = 25%), Asian Indians were more likely to report delayed care due to cost (2.58 (1.14,5.85)), while Other Asians were more likely to report no care due to cost (2.43 (1.09,5.44)) or delayed care due to cost (2.35 (1.14,4.86)), compared with Chinese. Results among Filipinos were not statistically significant. Conclusions: Among Asians living in the U.S. with cardiovascular risk factors or ASCVD, Asian Indians and Other Asians are more likely to report delayed care or no care due to cost compared with Chinese.

Statin Use and Risk of Diabetes by Subclinical Atherosclerosis Burden (from a Multi-Ethnic Study of Atherosclerosis Report).

Although there is a significant reduction in atherosclerotic cardiovascular disease risk with statins, a higher risk of diabetes mellitus has been demonstrated in randomized clinical trials. The risk of incident diabetes with statins may be heterogeneous by presence of coronary artery calcium (CAC). We evaluated participants without prevalent diabetes at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of subjects free of clinical cardiovascular disease at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between statin use and incident diabetes, adjusting for sociodemographic and cardiovascular risk factors, including time-varying statin use and stratifying by baseline CAC (0, 1 to 100, ≥100). The study population included 5,943 participants with a mean (SD) age of 62 (10) years, 54% women, 41% White, 26% Black, 12% Chinese-American, and 21% Hispanic. In the unadjusted analyses, statin use was associated with a higher risk of incident diabetes (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.27 to 2.06). After adjustment, this risk was no longer significant (HR 1.13, 95% CI 0.83 to 1.54). Although imprecise, the HR expressing the association of statins with diabetes was lower for those with CAC = 0 (HR 0.80, 95% CI 0.45 to 1.40) than for those with a higher CAC burden (HR 1.30, 95% CI 0.71 to 2.39 for CAC 1 to 100 and HR 1.39, 95% CI 0.85 to 2.28 for CAC ≥100), but this heterogeneity was not statistically significant. In conclusion, statin therapy was not significantly associated with incident diabetes mellitus in this observational study. The risk of incident diabetes did not significantly differ by baseline CAC.

Racial Disparity in Flu Vaccine Uptake Among Asian American Individuals: A National Health Interview Survey Study.

Vaccination coverage rates across Asian American subpopulations with atherosclerotic cardiovascular disease (ASCVD) and diabetes mellitus is not well-studied. We used data from the National Health Interview Survey (NHIS) from 2006 to 2018 and included participants with a history of ASCVD or diabetes. Vaccination coverage in White were compared with Chinese, Asian Indian, Filipino, and "other Asian" (Japanese, Korean, and Vietnamese) adults using univariable and multivariable logistic regression models. We included 50,839 participants, mean age 62.7 ± 0.1 years, 46.3% women, 89.1% US-born. Filipino (59%) and Asian Indian (56%) adults were less likely to receive influenza vaccine than "other Asians" (66%), Chinese (65%), and White (60%) participants (P < 0.001). In multivariable adjusted models, Chinese (OR = 1.66, 1.02-2.69), Asian Indian (OR = 1.50, 1.07-2.10), and "other Asian" ethnicity (OR = 1.81, 1.38-2.36) were associated with higher odds of receiving influenza vaccination compared with White. Influenza vaccine coverage remains suboptimal across all studied races/ethnicities.

Racial/Ethnic Disparities and Determinants of Sufficient Physical Activity Levels.

Introduction: Adequate physical activity is an integral requirement for achieving cardiovascular health. Physical inactivity is the fourth leading cause of death worldwide. Hence, it is important to identify racial/ethnic groups that are less likely to achieve sufficient physical activity levels, and to address barriers to meeting physical activity requirements. Methods: Cross-sectional data from the 2006-2015 National Health Interview Survey (NHIS) were used to compare self-reported sufficient physical activity among different racial/ethnic groups: non-Hispanic (NH) Whites, NH Blacks, NH Asians, and Hispanics in the United States. Sufficient physical activity was defined as ≥ 150 minutes per week of moderate-intensity physical activity, ≥ 75 minutes per week of vigorous-intensity physical activity, or ≥ 150 minutes per week of moderate and vigorous physical activity. Results: The study sample consisted of 296,802 individuals, mean age ± standard error age 46.4 ± 0.10 years, 52% women, 70% NH White, 12% NH Black, 5% NH Asian, and 14% Hispanic. The prevalence of sufficient physical activity in the overall population was 46%, while it was 48% among NH Whites, 39% among NH Blacks, 45% among NH Asians, and 40% among Hispanics. In multivariable-adjusted models (odds ratio; 95% confidence interval), NH Blacks (0.79; 0.64,0.97), NH Asians (0.72; 0.62,0.85) and Hispanics (0.71; 0.61,0.82) were significantly less likely to engage in sufficient physical activity compared with NH Whites. Older age, women, and low income were inversely associated with sufficient physical activity, while a college education or higher was associated directly with it. Conclusions: NH Black and Asian Americans and Hispanic adults were less likely to engage in sufficient physical activity levels compared with Whites. It is important to address barriers to meeting physical activity thresholds to help achieve optimal cardiovascular health.

Select drug-drug interactions with colchicine and cardiovascular medications: A review.

Several randomized clinical trials have demonstrated the clinical utility of colchicine in the prevention and management of various cardiovascular conditions, including secondary prevention of atherosclerotic cardiovascular disease, acute and chronic pericarditis, and atrial fibrillation. As a result, it is reasonable to anticipate increased use of colchicine within the cardiovascular specialty. However, colchicine is metabolized by cytochrome P450 3A4 (CYP3A4) and a substrate of the efflux transporter, P-glycoprotein (P-gp), creating the potential for clinically significant drug-drug interactions (DDIs). Therefore, when colchicine is administered concomitantly with other cardiovascular agents that inhibit CYP3A4 or P-gp, there is an increased risk of significant DDIs, potentially leading to negative sequelae. This article summarizes the evidence supporting the use of colchicine for cardiovascular disease, describes the mechanisms behind DDIs with select cardiovascular medications, and provides suggestions regarding colchicine dosing and management of DDIs to minimize the risk of poor tolerability and colchicine toxicity.

Independent Association of Lipoprotein(a) and Coronary Artery Calcification With Atherosclerotic Cardiovascular Risk.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk but have not been studied in combination. OBJECTIVES: This study sought to investigate the independent and joint association of Lp(a) and CAC with ASCVD risk. METHODS: Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and 3 CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor-adjusted Cox regression models. RESULTS: Among MESA participants (61.9 years of age, 52.5% women, 36.8% White, 29.3% Black, 22.2% Hispanic, and 11.7% Chinese), 476 incident ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (HR: 1.29; 95% CI: 1.04-1.61; HR: 1.68; 95% CI: 1.30-2.16; and HR: 2.66; 95% CI: 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR: 4.71; 95% CI: 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR: 1.31; 95% CI: 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS. CONCLUSIONS: Lp(a) and CAC are independently associated with ASCVD risk and may be useful concurrently for guiding primary prevention therapy decisions.