Rates Of Atherosclerotic Cardiovascular Disease Research Articles

Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention.

Despite growing evidence that apolipoprotein B (apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care. A sample of 293 876 UK Biobank adults (age: 40-73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included. Distribution of apoB at pre-specified levels of LDL-C, non-HDL-C, and triglycerides was examined graphically, and 10-year ASCVD event rates were compared for high vs. low apoB. Residuals of apoB were constructed after regressing apoB on LDL-C, non-HDL-C, and log-transformed triglycerides and used as predictors in a proportional hazards regression model for new-onset ASCVD adjusted for standard risk factors, including HDL-C. ApoB was highly correlated with LDL-C and non-HDL-C (Pearson's r = .96, P < .001 for both) but less so with log triglycerides (r = .42, P < .001). However, apoB ranges necessary to capture 95% of all observations at pre-specified levels of LDL-C, non-HDL-C, or triglycerides were wide, spanning 85.8-108.8 md/dL when LDL-C 130 mg/dL, 88.3-112.4 mg/dL when non-HDL-C 160 mg/dL, and 67.8-147.4 md/dL when triglycerides 115 mg/dL. At these levels (±10 mg/dL), 10-year ASCVD rates for apoB above mean + 1 SD vs. below mean - 1 SD were 7.3 vs. 4.0 for LDL-C, 6.4 vs. 4.6 for non-HDL-C, and 7.0 vs. 4.6 for triglycerides (all P < .001). With 19 982 new-onset ASCVD events on follow-up, in the adjusted model, residual apoB remained statistically significant after accounting for LDL-C and HDL-C (hazard ratio 1.06, 95% confidence interval 1.0-1.07), after accounting for non-HDL-C and HDL-C (hazard ratio 1.04, 95% confidence interval 1.03-1.06), and after accounting for triglycerides and HDL-C (hazard ratio 1.13, 95% confidence interval 1.12-1.15). None of the residuals of LDL-C, non-HDL-C, or of log triglycerides remained significant when apoB was included in the model. High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non-HDL-C, and triglycerides are not adequate proxies for apoB in clinical care.

Race and Ethnicity With Atherosclerotic Cardiovascular Disease Outcomes Within a Universal Health Care System: Insights From the CARTaGENE Study.

It remains unclear whether racial and ethnic disparities for atherosclerotic cardiovascular disease (ASCVD) persist within universal health care systems. We aimed to explore long-term ASCVD outcomes within a single-payer health care system with extensive drug coverage in Québec, Canada. CARTaGENE (CaG) is a population-based prospective cohort study of individuals aged 40 to 69 years. We included only participants without previous ASCVD. The primary composite endpoint was time to the first ASCVD event (cardiovascular death, acute coronary syndrome, ischemic stroke-transient ischemic attack, or peripheral arterial vascular event). The study cohort included 18,880 participants followed for a median of 6.6 years (2009 to 2016). The mean age was 52 years, and 52.4% were female. After further adjustment for socioeconomic and cardiovascular factors, the increase in ASCVD risk for South Asians (SAs) was attenuated (hazard ratio [HR], 1.41; 95% confidence interval [CI], 0.75, 2.67), whereas Black participants' risk was lower (HR, 0.52; 95% CI, 0.29, 0.95) compared with White participants. After similar adjustments, there were no significant differences in ASCVD outcomes among the Middle Eastern, Hispanic, East-Southeast Asian, Indigenous, and mixed race-ethnicities participants and the White participants. After adjustment for CV risk factors, the risk of ASCVD was attenuated in the SA CaG participants. Intensive risk-factor modification may mitigate the ASCVD risk of the SAs. Within a universal health care context and comprehensive drug coverage, the ASCVD risk was lower among Black compared with White CaG participants. Future studies are needed to confirm whether universal and liberal access to health care and medications can reduce the rates of ASCVD among the Black population.

Clinical characteristics of adult and paediatric patients with familial hypercholesterolemia: A real-life cross-sectional study from the Turkish National Database

Background and aimsFamilial hypercholesterolemia (FH) is the most common cause of premature atherosclerotic cardiovascular disease (ASCVD). Türkiye is among the countries with the highest rate of ASCVD. However, no population-based study has been published so far on the prevalence of FH, demographic and clinical characteristics, burden of ASCVD, treatment compliance, and attainment of low-density lipoprotein cholesterol (LDL-C) targets. MethodsWe performed a study using the Turkish Ministry of Health's national electronic health records involving 83,063,515 citizens as of December 2021 dating back 2016. Adults fulfilling the diagnostic criteria of definite or probable FH according to the Dutch Lipid Network Criteria (DLNC), and children and adolescents fulfilling the criteria of probable FH according to the European Atherosclerosis Society (EAS) Consensus Panel report formed the study population (n = 157,790). The primary endpoint was the prevalence of FH. ResultsProbable or definite FH was detected in 0.63% (1 in 158) of the adults and 0.61% (1 in 164) of the total population. The proportion of adults with LDL-C levels >4.9 mmol/L (190 mg/dL) was 4.56% (1 in 22). The prevalence of FH among children and adolescents was 0.37% (1 in 270). Less than one-third of the children and adolescents, and two-thirds of young adults (aged 18–29) with FH were already diagnosed with dyslipidaemia. The proportion of adults and children and adolescents on lipid-lowering treatment (LLT) was 32.1% and 1.5%, respectively. The overall discontinuation rate of LLT was 65.8% among adults and 77.9% among children and adolescents. Almost no subjects on LLT were found to attain the target LDL-C levels. ConclusionsThis nationwide study showed a very high prevalence of FH in Türkiye. Patients with FH are diagnosed late and treated sub-optimally. Whether these findings may explain the high rates of premature ASCVD in Türkiye needs further investigation. These results denote the urgent need for country-wide initiatives for early diagnosis and effective management of FH patients.

COMBINSI (COMBat to INSufficient Insulin therapy) – A Portuguese project in type 2 diabetes

BackgroundInadequate glycemic control in type 2 diabetes (T2D) increases the risk of diabetes-related complications. Insulin initiation is often delayed for several years. This study aims to estimate the adequacy of insulin therapy prescription to people living with T2D in a primary care setting. Material and methodsThis was a cross-sectional study based on adults with T2D in a Portuguese local health unit between January 2019 and January 2020. Subjects under insulin therapy were compared with non-insulin-treated subjects with Hemoglobin A1c (HbA1c) ≥9% regarding clinical and demographic characteristics. The proportion of insulin-treated subjects in both of these groups was defined as insulin therapy index. ResultsOur study included 13,869 adults living with T2D, among whom 11.5% were treated with insulin therapy and 4.1% had HbA1c ≥ 9% and were not under insulin therapy. Insulin therapy index was 73.9%. When comparing with non-insulin-treated subjects with HbA1c ≥ 9%, insulin-treated subjects were significantly older (75.8 vs 66.2 years p < 0.001), had lower HbA1c (8.3 vs 10.3% p < 0.001), lower estimated glomerular filtration rate (66.4 vs 74.0 ml/min/1.73 m2p < 0.001), lower LDL-cholesterol (87.1 vs 105.8 mg/dl), and higher rates of atherosclerotic cardiovascular disease (32.7 vs 16.7% p < 0.001). ConclusionInsulin therapy is underprescribed in T2D, with over 1-in-4 people living with T2D not being prescribed insulin despite deficient glycemic control. These findings highlight the need for insulin therapy when glycemic control is inadequate under other interventions.

Estimating the Prevalence of Hypercholesterolemia in Indigenous Populations: A Systematic Review and Meta-Analysis

BackgroundHypercholesterolemia is a common condition characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of atherosclerotic cardiovascular disease (ASCVD). Indigenous populations experience disproportionate rates of ASCVD, however, the extent to which hypercholesterolemia contributes to this burden is unknown. ObjectivesThis study aimed to estimate the prevalence of hypercholesterolemia, severe hypercholesterolemia, and familial hypercholesterolemia (FH) in Indigenous populations in Canada, the United States, Australia, and New Zealand. MethodsWe searched MEDLINE, EMBASE, Web of Science, Native Health Database, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for peer-reviewed studies reporting on hypercholesterolemia and elevated LDL-C in Indigenous populations. All diagnostic criteria used to classify hypercholesterolemia were included. Pooled prevalence and 95% CIs were calculated using a random-effects model. ResultsThere were no studies reporting the prevalence of FH and one study reporting the prevalence of severe hypercholesterolemia in Indigenous populations. The pooled prevalence of hypercholesterolemia was 28.9% or ∼1 in 3 to 1 in 4 individuals (95% CI: 22.4%-36.4%) and 12.6% (95% CI: 7.7%-19.9%) using an LDL-C cutoff of ≥3.5 mmol/L (135 mg/dL). The pooled prevalence in Indigenous populations in North America was 24.3% (95% CI: 17.1%-33.3%) compared with 40.0% (95% CI: 31.3%-49.3%) in Australia. Meta-regression showed diabetes had a significant effect on prevalence (P = 0.022). ConclusionsHypercholesterolemia is prevalent in Indigenous communities and may contribute to the high burden of ASCVD these populations face. There is insufficient research on FH and severe hypercholesterolemia in Indigenous populations worldwide.

Estimated versus observed 10-year atherosclerotic cardiovascular event rates in a rural population-based health initiative: The Heart of New Ulm Project

ObjectiveAssess discrepancy between estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk and observed 10-year event rates in a rural population participating in cardiovascular health initiative. MethodsThe study included a rural sample of individuals participating in the Heart of New Ulm (HONU), a population-based health initiative aimed at reducing ASCVD risk in a rural community. HONU conducted over 100 baseline screening events with 5221 individuals participating in 2009. For this analysis, we included participants who were aged 40–79 years, free of ASCVD at baseline, and had adequate data to calculate 10-year ASCVD risk. Electronic health record data and state death records were used to determine rates of non-fatal myocardial infarction and stroke, and ASCVD death from 2010–2019. ASCVD event rates were compared to estimated 10-year risks calculated using the Pooled Cohort Equations, stratified by sex and clinically relevant risk categories. ResultsThe sample (n = 2819, mean ± SD age 56.1 ± 9.9 years, 59.6% female) had a low prevalence of tobacco use (8.1% current smokers) and diabetes (6.5%) and a high prevalence of hypertension (44.4%) and hyperlipidemia (56.6%). The median estimated 10-year ASCVD risk for the entire sample was 5.7% (IQR 2.3–13.5%) with an observed 10-year ASCVD event rate of 3.4%. The largest gap between observed and estimated risk was in those at intermediate/high (≥7.5%) ASCVD risk (median 10-year risk 15.8% [IQR 10.4–29.0], observed ASCVD event rate 6.4%). ConclusioIn a sample of rural participants exposed to a multifaceted ASCVD prevention initiative, observed rates of ASCVD were substantially lower compared to estimated ASCVD risk. The potential for significantly lower than predicted ASCVD event rates in certain populations should be included in the clinician-patient risk discussion.

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

IntroductionSome 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.MethodsCross-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.ResultsThe 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.ConclusionsAmong 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.

Coronary Artery Calcium Score to Refine the Use of PCSK9i in Asymptomatic Individuals: A Multicohort Study

BackgroundThe value of coronary artery calcium (CAC) in the allocation of PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitors) among individuals without clinically evident atherosclerotic cardiovascular disease (ASCVD) is unknown for indications that do not require confirmed familial hypercholesterolemia. We aimed to assess the ability of CAC to stratify ASCVD risk under 3 non–familial hypercholesterolemia PCSK9i allocation paradigms.Methods and ResultsWe included participants without clinically evident ASCVD from MESA (Multi‐Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults) study, DHS (Dallas Heart Study), and HNR (Heinz Nixdorf Recall) study. Three PCSK9i eligibility scenarios were defined: a broad scenario informed only by high low‐density lipoprotein cholesterol levels (N=567), a restrictive one combining higher low‐density lipoprotein cholesterol levels and presence of ≥2 additional risk factors (N=127), and a high‐risk scenario where individuals with subclinical organ damage or high estimated risk would be treated to achieve low‐density lipoprotein cholesterol <55 mg/dL (N=471). The high‐risk scenario had the highest ASCVD event rates (27.8% at 10 years). CAC=0 was observed in 35% participants in the broad scenario, 25% in the restrictive scenario, and 16% in the high‐risk scenario. In all, CAC=0 was associated with the lowest incident ASCVD rates at 5 and 10 years, and CAC burden was independently associated with ASCVD events adjusting for traditional risk factors.ConclusionsCAC may be used to refine the allocation of PCSK9i, potentially leading to a more conservative use if CAC=0. The value of CAC testing is greater in scenarios that use low‐density lipoprotein cholesterol levels and/or traditional risk factors to define PCSK9i eligibility (CAC=0 present in 1 of 3–4 patients), whereas its prevalence is lower when allocation is informed by presence of noncoronary subclinical organ damage.

High lipoprotein(a) levels predict severity of coronary artery disease in patients hospitalized for acute myocardial infarction. Data from the French RICO survey

Lipoprotein(a) (Lp(a)) is a well-recognized independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, limited data are available on the relationship between coronary artery disease (CAD) burden and Lp(a) levels in patients with acute myocardial infarction (MI). The objective of this study was to assess the severity of CAD according to Lp(a) levels from a French regional registry of acute MI. CAD burden was assessed in 1213 consecutive patients hospitalized for acute MI in 2019-2020 who underwent coronary angiography. Patients were compared according to their Lp(a) levels: <50 mg/dL (normal), ≥50 mg/dL and ≤100 mg/dL (high) and >100 mg/dL (very high). The prevalence of high and very high Lp(a) was 13% and 6%, respectively. Median age, and rates of diabetes and smoking were similar in all groups. Patients with high or very high Lp(a) were more often under statin therapy, their corrected LDL-cholesterol levels were lower and previous ASCVD rates higher. When compared with lower levels, patients with very high Lp(a) levels had more elevated SYNTAX scores and more frequent multivessel disease. By multivariate logistic regression analysis, the odd ratio for the estimate of multivessel disease was the highest for patients with Lp(a) >100 mg/dL. Moreover, there was a gradual increase in the number of in-hospital deaths across the three Lp(a) groups (p=0.028). In real-world patients hospitalized for acute MI in France, very high Lp(a) levels are independently associated with a severe CAD burden, supporting the need for systematic screening of Lp(a) in these patients.

Serum Low-Density Lipoprotein Cholesterol and Cardiovascular Disease Risk Across Chronic Kidney Disease Stages (Data from 1.9 Million United States Veterans)

In the general population, elevated low-density lipoprotein (LDL) cholesterol levels are an important risk factor for cardiovascular disease (CVD) and mortality; however, the association of LDL with mortality risk and cardiovascular events are less clear in chronic kidney disease (CKD). We sought to examine the relationship of LDL with mortality and rates of atherosclerotic cardiovascular disease (ASCVD) and non-atherosclerotic cardiovascular-related (non-ASCVD) hospitalizations across CKD stages. Our analytical cohort consisted of 1,972,851 United States veterans with serum LDL data between 2004 and 2006. Associations of LDL with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models with adjustment for demographics, comorbid conditions, smoking status, prescription of statins and non-statin lipid-lowering drugs, body mass index, albumin, high-density lipoprotein, and triglycerides. Associations between LDL and ASCVD and non-ASCVD hospitalizations were estimated using negative binomial regression models across CKD stages. The cohort consisted of 5% female, 14% Black, 29% diabetic, 33% statin-users, and 44% current smokers, with a mean patient age of 64 ± 14 years. Patients with high LDL (≥160 mg/dL) had a higher risk of all-cause and cardiovascular mortality as well as ASCVD and non-ASCVD hospitalization rates across all CKD stages compared with the reference (LDL 70 to <100 mg/dL). The associations with all-cause and cardiovascular mortality and ASCVD hospitalization rate were attenuated at higher CKD stages. These trends were reversed with amplification of the association of high LDL with non-ASCVD hospitalization at higher CKD stages. In conclusion, associations of LDL with mortality and both ASCVD and non-ASCVD hospitalizations are modified according to kidney disease stage.

Association of Coronary Plaque With Low-Density Lipoprotein Cholesterol Levels and Rates of Cardiovascular Disease Events Among Symptomatic Adults

Atherosclerosis burden and coronary artery calcium (CAC) are associated with the risk for atherosclerotic cardiovascular disease (ASCVD) events, with absence of plaque and CAC indicating low risk. Whether this is true in patients with elevated levels of low-density lipoprotein cholesterol (LDL-C) is not known. Specifically, a high prevalence of noncalcified plaque might signal high risk. To determine the prevalence of noncalcified and calcified plaque in symptomatic adults and assess its association with cardiovascular events across the LDL-C spectrum. This cohort study included symptomatic patients undergoing coronary computed tomographic angiography from January 1, 2008, to December 31, 2017, from the seminational Western Denmark Heart Registry. Follow-up was completed on July 6, 2018. Data were analyzed from April 2 to December 2, 2021. Prevalence of calcified and noncalcified plaque according to LDL-C strata of less than 77, 77 to 112, 113 to 154, 155 to 189, and at least 190 mg/dL. Severity of coronary artery disease was categorized using CAC scores of 0, 1 to 99, and ≥100, where higher numbers indicate greater CAC burden. Atherosclerotic cardiovascular disease events (myocardial infarction and stroke) and death. A total of 23 143 patients with a median age of 58 (IQR, 50-65) years (12 857 [55.6%] women) were included in the analysis. During median follow-up of 4.2 (IQR, 2.3-6.1) years, 1029 ASCVD and death events occurred. Across all LDL-C strata, absence of CAC was a prevalent finding (ranging from 438 of 948 [46.2%] in patients with LDL-C levels of at least 190 mg/dL to 4370 of 7964 [54.9%] in patients with LDL-C levels of 77-112 mg/dL) and associated with no detectable plaque in most patients, ranging from 338 of 438 (77.2%) in those with LDL-C levels of at least 190 mg/dL to 1067 of 1204 (88.6%) in those with LDL-C levels of less than 77 mg/dL. In all LDL-C groups, absence of CAC was associated with low rates of ASCVD and death (6.3 [95% CI, 5.6-7.0] per 1000 person-years), with increasing rates in patients with CAC scores of 1 to 99 (11.1 [95% CI, 10.0-12.5] per 1000 person-years) and CAC scores of at least 100 (21.9 [95% CI, 19.9-24.4] per 1000 person-years). Among those with CAC scores of 0, the event rate per 1000 person-years was 6.3 (95% CI, 5.6-7.0) in the overall population compared with 6.9 (95% CI, 4.0-11.9) in those with LDL-C levels of at least 190 mg/dL. Across all LDL-C strata, rates were similar and low in those with CAC scores of 0, regardless of whether they had no plaque or purely noncalcified plaque. The findings of this cohort study suggest that in symptomatic patients with severely elevated LDL-C levels of at least 190 mg/dL who are universally considered to be at high risk by guidelines, absence of calcified and noncalcified plaque on coronary computed tomographic angiography was associated with low risk for ASCVD events. These results further suggest that atherosclerosis burden, including CAC, can be used to individualize treatment intensity in patients with severely elevated LDL-C levels.

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

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. 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. 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). Current cigarette smoking, diabetes, and hypertension are independently associated with incident ASCVD over a 16-year follow-up among those with CAC=0.

Vitamin D deficiency in diabetes exacerbates longitudinal risk for atherosclerotic cardiovascular disease in Lanzhou, China.

Vitamin D deficiency has been considered a risk factor for atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to investigate the correlation between serum 25(OH)D concentration and the risk of ASCVD in Chinese, especially in Type 2 diabetes mellitus (T2DM) patients. Based on the "REACTION" study conducted in 2011, some 9,014 Lanzhou residents aged 40-75 years were followed from 2014 to 2016. A total of 7,061 with complete data were analyzed. Baseline population was classified into four groups based on 25(OH)D quartiles. Cox proportional hazard models were used to estimate relations between 25(OH)D concentration and ASCVD. The prevalence of vitamin D deficiency [25(OH)D <20 ng/mL] was 75.1%. Followed-up for 3.3 years, those with the lowest of 25(OH)D concentration had higher rates of ASCVD (HR: 1.748, 95% CI: 1.149-2.660, p<0.01). A 10 ng/mL increase in baseline serum 25(OH)D was accompanied by a 24 % decrease in ASCVD risk (HR: 0.760, 95% CI: 0.590-0.980, p<0.05). For 25(OH)D and ASCVD risk with glycaemic status, low 25(OH)D plus T2DM was highly associated with ASCVD (HR: 2.296, 95% CI: 1.246-4.232, p<0.01). With diabetes, ASCVD risk decreased by 36% when serum 25(OH)D increased by 10 ng/mL (HR: 0.644, 95% CI: 0.440-0.941, p<0.05). Serum 25(OH)D is independently and inversely associated with the risk of ASCVD in Lanzhou Chinese, especially those with T2DM. Maintaining sufficient levels of vitamin D may be an effective measure in ASCVD prevention.

Abstract 9969: Determinants of Incident Atherosclerotic Cardiovascular Disease Events Among Individuals with Absent Coronary Artery Calcium: Results from the Multi-Ethnic Study of Atherosclerosis

Introduction: We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) among individuals with absent coronary artery calcium (CAC=0) over long-term follow-up. Methods: We included participants with CAC=0 at baseline from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of individuals free of clinical ASCVD at baseline. After calculating crude event rates, we used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors [cigarette smoking, diabetes mellitus, 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 events. Results: The study population consisted of 3,416 individuals with CAC=0 (mean (SD) age 58 (9) years; 63% were female, 33% White, 31% Black, 12% Chinese-American, and 24% Hispanic. At a median follow-up of 16 years, there were 189 ASCVD events (101 CHD, 98 stroke). The unadjusted 16-year incidence rates of ASCVD were ≤5 per 1000-person-years among individuals with CAC=0 with the exception of current cigarette smoking (7.30), diabetes mellitus (8.92), hypertension (5.44), and chronic kidney disease (6.75). ASCVD event rates were 6.19 per 1000 person-years among those with estimated baseline ASCVD risk 7.5%–&lt;15% and 5.87 per 1000 person-years among those with estimated ASCVD risk 15%–&lt;20%. After multivariable-adjustment, risk factors that were significantly associated with ASCVD: hazard ratio (HR) 95% confidence interval (CI) included current cigarette smoking: 2.12 (1.32,3.42), diabetes mellitus: 1.68 (1.01,2.80), and hypertension: 1.57 (1.06,2.33). Conclusion: In a middle-age population free of ASCVD at baseline, current cigarette smoking, diabetes mellitus, and hypertension are independently associated with incident ASCVD over 16-year follow-up among those with CAC=0. If considering a long treatment horizon, it may be reasonable to continue to recommend statin therapy in the presence of these risk factors despite the absence of CAC.

High levels of lipoprotein(a) are associated with the severity of coronary disease in patients with acute myocardial infarction. Data from the RICO survey

Abstract Background High level of lipoprotein(a), Lp(a), is a well-recognized independent risk factor for atherosclerotic cardiovascular disease (ASCVD) including acute myocardial infarction (MI). However, limited data are available on the relationship between coronary artery disease (CAD) burden and Lp(a) levels in patients with acute MI. Methods CAD burden was addressed in 1213 consecutive patients hospitalized for an acute MI in 2019–2020 who underwent coronary angiography from the RICO survey. Patients were compared according to Lp(a) levels (Lp(a) &amp;lt;50 mg/dL (normal), ≥50 mg/dL and ≤100 mg/dL (high) and &amp;gt;100 mg/dL (very high)). Results The prevalence of high and very high Lp(a) was elevated (13% and 6%, respectively). Median (IQR) age (normal: 68 (58–79)y; high: 70 (61–80)y; very high: 69 (60–78)y, p=0.502) and rate of diabetes (p=0.448) were similar across the 3 groups. When compared with normal Lp(a), patients with very high Lp(a) had more frequently hypertension, were more often under chronic statin therapy and their corrected LDL-cholesterol was lower. There was a gradual increase in prior ASCVD rates across the 3 Lp(a) groups (p=0.001). When compared with patients with high or normal Lp(a), patients with very high Lp(a) levels had elevated SYNTAX score at coronary angiography, (17 (6–25) vs 12 (6–19) and 10 (5–18), p=0.006, respectively), and had more frequently multivessel disease (74% vs 64% and 56%, p=0.003). By multivariate analysis, very high Lp(a) (OR(95% CI): 1.879 (1.065–3.312)) remained associated with high CAD burden, beyond confounding including age, diabetes and dyslipidemia. Conclusion Among real world patients hospitalized for an acute MI, high Lp(a) levels are common (≈20%) and independently associated with a severe CAD burden, beyond traditional risk factors, identifying a subset of patients with features of high ASCVD risk. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): CHU Dijon Bourgogne ARS Bourgogne Franche Comté

Prevention of Atherosclerotic Cardiovascular Disease in Children with Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH), a common inherited disorder of LDL-C metabolism that predisposes to premature cardiovascular disease, is underdiagnosed. Despite recommendations for screening all children and initiation of lipid-lowering medication beginning at 8-10years of age, adherence to guidelines is low. Most individuals with FH are inadequately treated, especially women and children. The purpose of this review is to discuss current literature and recommendations for the diagnosis and treatment of heterozygous FH (HeFH) in the pediatric population. Twenty-year outcome data demonstrate lower rates of atherosclerotic cardiovascular disease (ASCVD) related events and death in individuals with FH who were treated with statins from childhood, compared to those who initiated statins in adulthood. While diagnosis rates of FH are slowly improving, most clinicians do not adhere to recommendations for cholesterol screening in youth. Identifying youth with FH offers the opportunity for early intervention to prevent ASCVD and identify affected relatives through reverse cascade screening.

Prevention of atherosclerotic cardiovascular disease in South Asians in the US: A clinical perspective from the National Lipid Association

It is now well recognized that South Asians living in the US (SAUS) have a higher prevalence of atherosclerotic cardiovascular disease (ASCVD) that begins earlier and is more aggressive than age-matched people of other ethnicities. SA ancestry is now recognized as a risk enhancer in the US cholesterol treatment guidelines. The pathophysiology of this is not fully understood but may relate to insulin resistance, genetic and dietary factors, lack of physical exercise, visceral adiposity and other, yet undiscovered biologic mechanisms. In this expert consensus document, we review the epidemiology of ASCVD in this population, enumerate the challenges faced in tackling this problem, provide strategies for early screening and education of the community and their healthcare providers, and offer practical prevention strategies and culturally-tailored dietary advice to lower the rates of ASCVD in this cohort.

Familial hypercholesterolemia and cardiovascular disease in older individuals

Background and aimsFamilial hypercholesterolemia (FH) is characterized by high LDL-cholesterol (LDL-C) and early atherosclerotic cardiovascular disease (ASCVD). With a lipid lowering therapy (LLT), most individuals with FH may have a longer ASCVD-free survival. However, there is scant data about older individuals with FH. MethodsWe compared characteristics of genetically defined FH older individuals with age-matched non-FH counterparts. ResultsFrom 4111 genotyped individuals, 462 older than 60 years were included (198 positive and 264 negative for FH variants). There were no differences regarding median age [%25; 75%] 66.0 (62.0; 71.0) and 66.0 (62.2; 71.0) years, p = 0.68 for FH and non-FH, respectively. In both groups, there was a higher frequency of females, however, there were more males in the FH group 37.4% vs. 24.2%, p = 0.002. No differences were seen between FH and non-FH in LLT use: 88.5% vs. 91.5%, p = 0.29. Despite a longer LLT duration in FH patients (with 11.0 (7.0; 20.0) vs. 7.0 (3.0; 13.0) years, p < 0.001), treatment was started late in both groups: at 54.0 (47.0; 61.0) and 59.0 (52.0; 64.0) years, p < 0.001, in FH and non-FH, respectively. FH had greater frequencies of previous and early ASCVD (40.9% vs. 27.3%, p = 0.002, and 22.2% vs. 9.0%, p < 0.001). In FH, male sex [HR (95%CI)] 2.67 (1.50–4.73), p = 0.001, and LLT onset age 0.96 (0.93–0.99), p = 0.009, were independently associated with ASCVD. ConclusionsAmong hypercholesterolemic older individuals participating in a cascade screening program, the genetic diagnosis of FH was associated with higher ASCVD rates, emphasizing the relevance of a monogenic defect as the cause of long-lasting hypercholesterolemia and ASCVD risk, particularly in men.

Distribution of calcium volume, density, number, and type of coronary vessel with calcified plaque in South Asians in the US and other race/ethnic groups: The MASALA and MESA studies

Background and aimsSouth Asians (SA) experience disproportionately higher rates of atherosclerotic cardiovascular disease (ASCVD) events than non-Hispanic whites (NHW) and several other Asian groups. The coronary artery calcium (CAC) Agatston score may not capture the unique characteristics of coronary plaque in SA. We therefore evaluated the prevalence and patterns of advanced CAC measures (specific coronary vessel involvement, CAC volume and density) in SA versus other race/ethnicities. MethodsWe combined data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts. We used multivariable-adjusted linear regression models to compare advanced CAC measures between SA and other ethnicities. ResultsOur analyses included 7,625 individuals (810 SA, 2,622 whites, 1,893 African Americans, 1,496 Hispanics, 803 Chinese Americans) with mean (SD) age 62 (10) years and 48% men. In adjusted analyses, compared to NHW, SA had lower overall CAC volume [beta coefficient (95% CI)] [-0.46 (−0.62,-0.29)] but higher overall CAC density [0.14 (0.11,0.18)]. These trends were similar when SA were compared to non-whites (Hispanics, Chinese Americans, and African Americans). SA had higher overall [0.07 (0.03,0.12)] and right coronary artery [0.09 (0.03,0.16)] CAC density compared to non-whites, while CAC volume was not significantly different between these two groups. ConclusionsSA have lower CAC volume compared to NHW but similar compared to non-whites. Overall CAC density is higher among SA compared to NHW and non-whites. Future longitudinal studies of ASCVD events are required to confirm the prognostic significance of these findings among SA.

Abstract 14662: Relationships Between Physical Activity, Coronary Artery Calcium, and Cardiovascular Outcomes in the Multi-Ethnic Study of Atherosclerosis: MESA

Introduction: Physical activity is associated with decreased rates of atherosclerotic cardiovascular disease (ASCVD) and mortality. However, high levels of physical activity (PA) have paradoxically been linked with elevated levels of coronary artery calcium (CAC). It remains unclear whether high levels of physical activity in the presence of high CAC are associated with adverse outcomes in a diverse, multi-ethnic population. Hypothesis: We hypothesized that high compared to low levels of PA are associated with a reduction in incident ASCVD and all-cause mortality, even in the presence of high CAC. Methods: Baseline total PA (MET-min/week) in the Multi-Ethnic Study of Atherosclerosis (MESA), obtained via questionnaire, was divided into quartiles. CAC was dichotomized into low (CAC &lt;100 Agatston Units (AU)) and high (CAC ≥100 AU) categories. Outcomes of interest included ASCVD and all-cause mortality. Cox proportional hazard regression analysis was used to assess associations between PA, ASCVD, and all-cause mortality among low and high CAC groups. Results: Among the 6,814 participants included in this study, the average age was 62 years, 53% were female, and 38% were non-Hispanic white. In participants with CAC &lt;100 AU and PA in the highest quartile, we observed a significant reduction in ASCVD and all-cause mortality compared with participants in the lowest PA quartile (Table1). In participants with CAC ≥100 AU and PA in the highest quartile, we observed a significant reduction in all-cause mortality, but no difference in the risk of ASCVD compared with participants in the lowest PA quartile. Conclusions: Our study suggests that high levels of PA are associated with a reduced risk of ASCVD and all-cause mortality among individuals with low CAC, and a reduced risk of all-cause mortality among individuals with high CAC. There was no evidence to suggest an increased risk of ASCVD from high levels of PA in individuals with high CAC.