Incident Coronary Artery Calcification Research Articles

Abstract 4134911: Coronary Artery Calcium Predicts Cardiovascular Events in Individuals with Controlled Atherosclerotic Risk Factors: A Multi-Cohort Study

Background: There is residual risk of atherosclerotic cardiovascular disease (ASCVD) that remains despite adequate risk factor (RF) control. Coronary artery calcium (CAC) has demonstrated value in ASCVD risk stratification. We evaluated the value of CAC in identifying residual risk of ASCVD events among those with traditional RF control. Methods: Participants without clinical ASCVD were pooled from the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. RF control was classified as “guideline-concordant” and “optimal” (Figure 1). Participants were stratified by the number of controlled RFs at baseline and CAC score (CAC = 0, 1-99, ≥100). Cox proportional hazards models examined the association between CAC and incident ASCVD events. Results: The study included 14,780 individuals (mean age 58 years (SD: 11), 54% female, 59% White, 27% Black, 50% CAC = 0). Over a median follow-up of 14.6 years, there were 1,441 incident ASCVD events. The distribution of CAC and ASCVD event incidence is shown in Panel A; 10% of those with 3 optimal RFs and 19% of those with 3 guideline-concordant RFs controlled had CAC > 100. The rate of ASCVD events decreased with more RFs controlled and increased with higher CAC. Overall, optimal RF control was associated with lower ASCVD event rates compared to guideline-concordant control. At every level of RF control, CAC > 100 was associated with increased HRs for incident ASCVD (Panel B). Those with CAC ≥ 100 and controlled RFs experienced ASCVD rates numerically comparable to or exceeding those with uncontrolled RFs but CAC = 0 (Panel A). Adjusted HR (95% CI) for ASCVD events with CAC > 100 compared to CAC = 0 was 5.0 (2.0, 12.9) in optimal RF control and 3.7 (2.6, 5.4) in guideline-concordant RF control. Conclusion: There is significant heterogeneity in residual ASCVD risk among those with optimal or guideline-concordant traditional RF control and CAC can help identify this risk. Irrespective of RF control, a higher CAC burden was associated with increased ASCVD risk. Future studies could use CAC testing to identify those with higher residual ASCVD risk despite effective traditional RF control to target for novel therapies.

Prospective association between the Cardiovascular Health Diet Index and subclinical atherosclerosis: the ELSA-Brasil cohort study.

The Cardiovascular Health Diet Index (CHDI) is a diet quality score based on the dietary guidelines of the American Heart Association for cardiovascular health, but with some adaptations, such as red meat, dairy, beans, and ultra-processed foods in its components. The CHDI has shown good relative validity parameters, however, its association with health outcomes is still unclear. Thus, our aim was to investigate the association between the CHDI score with subclinical atherosclerosis. Data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort were used. Subclinical atherosclerosis was assessed by measuring coronary artery calcification (CAC) at baseline (2008-2010) and second wave (2012-2014) and carotid intima-media thickness (cIMT) at baseline and at the third wave (2017-2019). The CHDI score (ranges from 0 to 110 points) was applied to dietary data obtained from a food frequency questionnaire at baseline. Poisson regression with robust variance, linear regression and linear mixed-effects models were used to evaluate the association of the CHDI score with CAC incidence (n 2,224), CAC progression (n 725), and changes in cIMT (n 7,341) over time, respectively. After a median 8-year follow-up period, a 10-point increase in the CHDI score was associated with a decrease in cIMT of 0.002 mm (95% CI -0.005; -0.001). No association was observed between the CHDI score and CAC incidence and progression after a 4-year follow-up period. Higher scores in the CHDI were prospectively associated with decreased subclinical atherosclerosis after an 8-year follow-up period.

Association of novel dietary and lifestyle inflammation scores with incidence and progression of coronary artery calcification in middle-late adulthood: a longitudinal cohort study

BackgroundDietary patterns and lifestyle factors can influence the intensity of systemic inflammation and, consequently, the development and progression of coronary artery calcification (CAC). This study aimed to explore the relationship between the inflammatory potentials of diet and lifestyle, as captured by novel dietary and lifestyle inflammation scores (DIS and LIS), with CAC incidence and progression.MethodsWe analyzed data on 5949 Black and White men and women ≥ 45 years old participating in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Baseline data on diet and lifestyle factors were collected from 2000 to 2002 and used to construct the DIS and LIS, which reflect the overall inflammatory potential of diet and lifestyle. Cox proportional hazard regression was used to calculate the hazard ratios (HR) and 95% confidence intervals (95% CI) for CAC incidence and progression across quartiles of DIS and LIS, adjusting for potential confounders.ResultsOver a median follow-up of 8.0 years, among 2638 participants with zero CAC score at baseline, 977 individuals developed positive scores, and 1681 out of 2561 participants showed CAC progression. For individuals in the highest (more pro-inflammatory) compared to the lowest (more anti-inflammatory) quartiles of the LIS, the multivariable-adjusted HR for CAC incidence was 1.35 (95% CI, 1.10–1.65; P trend < 0.002). This association was stronger among younger adults aged < 60 years compared to those aged ≥ 60 years, with respective values of 1.76 (1.34–2.30) and 1.02 (0.78–1.35) (P interaction < 0.001). However, the LIS was not significantly associated with the progression of existing CAC. Among the components of the LIS, a body mas index (BMI) ≥ 25 kg/m2 and current smoking were significant predictors for the incidence and progression of CAC, respectively. No significant association was found between DIS and CAC incidence and progression.ConclusionsLifestyle factors, through their impact on systemic inflammation, may be associated with a higher risk of CAC incidence in middle and late adulthood.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear. A total of 2395 participants (41.6% men; mean±SD age, 40.2±3.6 years) with initial CAC =0 from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included. Serial lipid measurements were obtained to calculate mean levels and variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides. CAC incidence was defined as CAC >0 at follow-up. During a mean follow-up of 9.0 years, 534 individuals (22.3%) exhibited CAC incidence. Higher mean levels of total cholesterol, LDL-C, and non-HDL-C were associated with a greater risk of future CAC incidence. Similarly, 1-SD increment of lipid variability, as assessed by variability independent of the mean, was associated with an increased risk of CAC incidence (LDL-C: hazard ratio, 1.139 [95% CI, 1.048-1.238]; P=0.002; non-HDL-C: hazard ratio, 1.102 [95% CI, 1.014-1.198]; P=0.022; and triglycerides: hazard ratio, 1.480 [95% CI, 1.384-1.582]; P<0.001). Combination analyses demonstrated that participants with both high lipid levels and high variability in lipid profiles (LDL-C and non-HDL-C) faced the greatest risk of CAC incidence. Specifically, elevated variability of LDL-C was associated with an additional risk of CAC incidence even in low mean levels of LDL-C (hazard ratio, 1.396 [95% CI, 1.106-1.763]; P=0.005). These findings remained robust across a series of sensitivity and subgroup analyses. Elevated variability in LDL-C and non-HDL-C during young adulthood was associated with an increased risk of CAC incidence in midlife, especially among those with high mean levels of atherogenic lipoproteins. These findings highlight the importance of maintaining consistently low levels of atherogenic lipids throughout early adulthood to reduce subclinical atherosclerosis in midlife. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005130.

Impact of Nonalcoholic Hepatic Steatosis on the Warranty Period of a Coronary Artery Calcium Score of 0: Results From the Multi-Ethnic Study of Atherosclerosis.

For individuals with a coronary artery calcium (CAC) score of 0, CAC rescans at appropriate timings are recommended, depending on individual risk profiles. Although nonalcoholic fatty liver disease, recently redefined as metabolic-associated fatty liver disease, is a risk factor for atherosclerotic cardiovascular disease events, its relationship with the warranty period of a CAC score of 0 has not been elucidated. A total of 1944 subjects from the MESA (Multi-Ethnic Study of Atherosclerosis) with a baseline CAC score of 0, presence or absence of nonalcoholic hepatic steatosis, and at least 1 follow-up computed tomography scan were included. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. The association between nonalcoholic hepatic steatosis and new CAC incidence (CAC score >0) was evaluated using a Weibull survival model. Nonalcoholic hepatic steatosis was identified in 268 (14%) participants. Participants with nonalcoholic hepatic steatosis had higher CAC incidence than those without nonalcoholic hepatic steatosis. Nonalcoholic hepatic steatosis was independently associated with new CAC incidence after adjustment for atherosclerotic cardiovascular disease risk factors (hazard ratio, 1.28 [95% CI, 1.05-1.57]; P=0.015). Using a 25% testing yield (25% of participants with zero CAC at baseline would be expected to have developed a CAC score >0), the warranty period of a CAC score of 0 in participants with nonalcoholic hepatic steatosis was shorter than in those without nonalcoholic hepatic steatosis (4.7 and 6.3 years). This association was consistent regardless of sex, race/ethnicity, age, and 10-year atherosclerotic cardiovascular disease risk. Nonalcoholic hepatic steatosis had an impact on the warranty period of a CAC score of 0. The study suggests that the time period until a CAC rescan should be shorter in those with nonalcoholic hepatic steatosis and a CAC score of 0.

The Relationship of Cardiorespiratory Fitness, Physical Activity, and Coronary Artery Calcification to Cardiovascular Disease Events in CARDIA Participants.

Moderate-to-vigorous-intensity physical activity (MVPA), cardiorespiratory fitness (CRF), and coronary artery calcification (CAC) are associated with cardiovascular disease (CVD) risk. While a U-shaped relationship between CRF or MVPA and CAC has been reported, the presence of CAC among highly fit individuals might be benign. We examined interactive associations of CRF or MVPA and CAC with outcomes and evaluated the relationship of CRF and MVPA to CAC incidence. CARDIA participants with CAC assessed in 2005-06 were included (n=3,141, mean age 45). MVPA was assessed by self-report and accelerometer. CRF was estimated with a maximal graded exercise test. Adjudicated CVD events and mortality data were obtained through 2019. CAC was reassessed in 2010-11. Cox models were constructed to assess hazard ratios (HRs) for CVD, coronary heart disease (CHD), and mortality in groups defined by CAC presence/absence and lower/higher CRF or MVPA levels. Logistic models were constructed to assess associations with CAC incidence. Adjustment was made for sociodemographic and CVD risk factors. Relative to participants with no CAC and higher CRF, the adjusted HRs for CVD were 4.68 for CAC and higher CRF, 2.22 for no CAC and lower CRF, and 3.72 for CAC and lower CRF. For CHD, the respective HRs were 9.98, 2.28, and 5.52. For mortality, the HRs were 1.15, 1.58, and 3.14, respectively. Similar findings were observed when MVPA, measured either by self-report or accelerometer, was substituted for CRF. A robust inverse association of CRF and accelerometer-derived MVPA with CAC incidence was partly accounted for by adjusting for CVD risk factors. In middle-aged adults, CRF and MVPA demonstrated an inverse association with CAC incidence but did not mitigate the increased cardiovascular risk associated with CAC, indicating that CAC is not benign in individuals with higher CRF or MVPA levels.

Progression of Coronary Artery Calcification and Risk of Clinical Events in CKD: The Chronic Renal Insufficiency Cohort Study

Coronary artery calcification (CAC) progresses rapidly in people with chronic kidney disease (CKD) compared with the general population. We studied the association between CAC progression and higher risks of atherosclerotic cardiovascular disease (CVD), congestive heart failure, and all-cause mortality among adults with CKD. Prospective cohort study. & Participants: 1,310 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had at least one CAC scan with no prior history of CVD and with observed or imputed data on changes in CAC over time. Observed or imputed CAC progression, categorized as incident CAC among participants with zero CAC on the baseline scan, or progressive CAC when the baseline scan demonstrated CAC and there was an increase in CAC ≥50 Agatston units per year. Atherosclerotic CVD (myocardial infarction or stroke), congestive heart failure, and all-cause mortality. Cause-specific Cox proportional hazards regression, stratified by presence of CAC at baseline. A total of 545 participants without and 765 with prevalent CAC at baseline were included. During a mean 3.3 years between CAC assessments, 177 (32.5%) participants without baseline CAC developed incident CAC while 270 participants (35.3%) with baseline CAC developed a ≥50 Agatston units per year increase in CAC. After multivariable adjustment, incident CAC was associated with 2.42-fold higher rate of atherosclerotic CVD (95% confidence interval [CI]: 1.23-4.79) and 1.82-fold higher rate of all-cause mortality (95% CI: 1.03-3.22). Progressive CAC (≥50 units per year) was not associated with atherosclerotic CVD (hazard ratio [HR]: 1.42; 95% CI: 0.85-2.35) but was associated with a 1.73-fold higher rate of all-cause mortality (95% CI: 1.31-2.28). Progressive CAC was not associated with incident heart failure. Residual confounding and limited statistical power for some outcomes. Among adults with CKD stages 2-4, CAC progression over a mean 3.3 years was associated with higher risk of atherosclerotic CVD and all-cause mortality. The associations were strongest among participants without CAC at baseline.

Association of Lipoprotein(a) with Progression of Coronary Artery Calcification: Retrospective Longitudinal Study.

Atherosclerotic cardiovascular disease (ASCVD) is a major health concern, and lipoprotein(a) (Lp(a)) is an independent risk factor. However, there is limited evidence regarding Lp(a) and the risk of ASCVD in Asian populations. This study aimed to assess the predictive value of changes in coronary artery calcification (CAC) for ASCVD risk associated with Lp(a) level. Participants (n=2,750) were grouped according to their Lp(a) levels, and the association between Lp(a) and CAC progression was examined. CAC progression was defined as the occurrence of incident CAC or a difference ≥2.5 between the square root (√) of baseline and follow-up coronary artery calcium scores (CACSs) (Δ√transformed CACS). To adjust for differences in follow-up periods, Δ√transformed CACS was divided by the follow- up period (in years). Over an average follow-up of 3.07 years, 18.98% of participants experienced CAC progression. Those with disease progression had notably higher Lp(a) levels. Higher Lp(a) tertiles correlated with increased baseline and follow-up CACS, CAC progression (%), and Δ√transformed CACS. Even after adjustment, higher Lp(a) levels were associated with CAC progression. However, annualized Δ√transformed CACS analysis yielded no significant results. This study demonstrated an association between elevated Lp(a) levels and CAC progression in a general population without ASCVD. However, longer-term follow-up studies are needed to obtain meaningful results regarding CAC progression. Further research is necessary to utilize Lp(a) level as a predictor of cardiovascular disease and to establish clinically relevant thresholds specific to the Korean population.

GlycA Levels Independently Predict Coronary Artery Calcium Incidence and Progression in the ELSA-Brasil Cohort (Brazilian Longitudinal Study of Adult Health)

Atherosclerosis is an inflammatory disease. Coronary artery calcium (CAC) is a marker of atherosclerotic disease events and mortality risk. Elevated GlycA, an emerging marker of inflammation, is associated with a higher risk for coronary artery disease (CAD). However, there is conflicting evidence on whether GlycA predicts subclinical CAD progression. We hypothesized that GlycA can predict subclinical CAC incidence/progression in healthy individuals. We included 2,690 ELSA-Brasil cohort participants without cardiovascular/chronic inflammatory disease not receiving statin therapy who had GlycA levels measured and two interval CAC assessments between 2010 through 2018. Multivariable logistic and linear regression models were computed to evaluate GlycA as a predictor of CAC incidence and progression. CAC incidence required a baseline CAC of 0. CAC progression required a baseline CAC > 0. The mean age of participants was 48.6 ± 7.7 years, 56.7% were female, 54.6% and 16.1% (429/2690) were White and Black, respectively. The mean CAC interscan period was 5.1 ± 0.9 years, the mean GlycA level was 414.7 ± 65 μmol/L, and the incidence of CAC was 13.1% (280/2,129). GlycA level odds ratio (OR) for CAC incidence was 1.002 [95% confidence interval (CI) 1.0005-1.005, p=0.016] adjusted for demographics, lifestyle, a family history of early CAD (≤60 years), lipids, and comorbidities. The GlycA (≤p25 vs ≥p75) OR for CAC progression (Berry definition) was 1.77 (95% CI 1.07-2.96, p=0.03) in a similar multivariable-adjusted model. Higher GlycA levels were associated with CAC incidence and progression in a healthy Brazilian cohort.

Abstract P113: Associations of Immune Cell Subsets With Coronary Artery Calcium Incidence and Progression in the Multi-Ethnic Study of Atherosclerosis

Introduction: Coronary artery calcium (CAC) and its progression strongly associates with incident cardiovascular disease (CVD). Although immune dysregulation and related inflammation are important causes of coronary artery disease, few data exist on associations between specific immune cell subsets and CAC presence and progression. Hypothesis: We hypothesized innate &amp; adaptive immune cell subsets are associated with longitudinal CAC changes Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), we examined associations of immune cell subsets (measured at baseline in peripheral blood by flow cytometry) with incident CAC and CAC progression. Of 975 participants sampled who had CAC and immune cell subsets measured at baseline (2000-02), 378 had CAC 0 at baseline and were used to examine incident CAC from MESA exam 2 (2002-04) through 5 (2010-12); the remaining 597 participants were included to analyze CAC progression from exam 1-5. Incident CAC analyses (N=378) used Weighted Cox regressions to determine hazard ratios of incident CAC, adjusted for age, gender, race, MESA site, education, smoking status, blood pressure, body-mass index, diabetes status, cholesterol, HDL cholesterol, statin use, and antihypertensive medication. CAC progression analyses among individuals with nonzero CAC at baseline (N=597) used weighted multivariable-adjusted linear mixed models to investigate associations of baseline immune cell subsets with CAC progression, with Benjamini-Hochberg correction for multiple comparisons. Results: Among 378 participants with CAC 0 and immune cell subsets measured at baseline, 149 had incident CAC between MESA examination 2-5. Of 19 subsets measured, natural killer (NK) cells (CD3-CD16+CD56+) were associated with an elevated risk of incident CAC (hazard ratio (HR) 1.26 per standard deviation (SD) higher NK cells; 95% confidence interval (CI) 1.03-1.56, p=0.03). Two CD4+ T cell subsets, Th1 (HR 0.81, 95% CI 0.66-0.99, p=0.04) and Th2 (HR 0.80, 95% CI 0.64-0.99, p=0.04) were associated with a borderline lower risk for incident CAC. In analyses of CAC progression for participants with nonzero CAC at baseline (N=597), CD19+ B-cells were associated with CAC progression (beta-coefficient=53.1 Agatston units per SD higher B-cells proportion, 95% CI 2.0-104.2, p=0.04), while intermediate monocytes (CD14+CD16+) (beta = -71.6 Agatston units per SD higher, 95% CI -134.9 - -8.3, p=0.03) and higher T-regulatory cells (CD4+CD25+CD127-) (beta = -71.6 Agatston units per SD higher, 95% CI -119.1 - -4.8, p=0.03) were negatively associated with CAC progression. Conclusions: Among individuals with CAC 0 at baseline, NK cells were associated with incident CAC. In individuals with nonzero CAC at baseline, T-regulatory cells and intermediate monocytes were negatively associated with CAC progression, whereas B-cells were positively associated with CAC progression.

Abstract 20: Dairy Consumption in Young Adulthood and Risk of Coronary Artery Calcification Later in Life

Introduction: The relationship of dairy with cardiovascular disease (CVD) remains controversial. Meta-analyses have shown a modest, protective association of dairy, and other recent evidence has indicated that whole-fat dairy may not be inferior to low-fat dairy, despite concerns about its saturated fat content. Hypothesis: Intakes of total, whole-fat and low-fat dairy during young adulthood are inversely associated with risk of incident coronary artery calcification (CAC), a subclinical marker of atherosclerosis and predictor of future CVD events. Methods: In 3,110 young adult participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study, dairy consumption was assessed via a validated diet history. Intake was averaged between baseline (1985-86) and year 7 exams. The first occurrence of CAC score &gt;0 among years 15, 20 and 25 was identified in 904 participants; the remainder were censored at the last available of these exams. Cox proportional hazards regression was used to estimate associations of CAC incidence with each of total, low-fat, and whole-fat dairy. Results: Median daily consumption of total dairy was 1.2 servings in quartile 1 and 5.4 servings in quartile 4. After adjustment for energy intake and other variables, associations of total and low-fat dairy with CAC were null. However, a monotonic trend was observed across quartiles of whole-fat dairy intake, where individuals in the highest quartile had a lower risk of CAC (hazard ratio: 0.74 (0.60, 0.93)) compared to those in the lowest quartile. Conclusions: Whole-fat dairy showed an inverse association with CAC 15 to 25 years later. Possible explanations for this finding include potentially cardioprotective effects of the unique profile of fatty acids or other fat-soluble constituents found in dairy products, as well as the displacement of foods and beverages in the diet. These results challenge dietary guidelines that recommend replacing whole-fat dairy with low-fat alternatives.

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

Background and aimsSouth 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. MethodsWe 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). ResultsWe 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]. ConclusionsOptimal 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.

Impact of optimal cholesterol levels on subclinical atherosclerosis in the absence of risk factors in young adults

Background and aimsWe aimed to assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs). MethodsA total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32–46 years free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL. Results1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30–1.36), incidence (1.30–1.32), and progression (1.31–1.35) of coronary artery calcium (CAC) and a 42–44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 μm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures. ConclusionsAmong adults aged 32–46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy.

Nontraditional Risk Markers for Incident Coronary Artery Calcium Among Persons ≥65 Years of Age

BackgroundThe initiation of coronary artery calcium (CAC) is an important physiologic milestone associated with increased cardiovascular disease risk. However, traditional risk factors (RF) do not perform well for predicting incident CAC among the 54 million older U.S. adults. ObjectivesThe authors sought to assess the association between nontraditional cardiovascular disease RF and incident CAC in older persons. MethodsThere were 815 MESA (Multi-Ethnic Study of Atherosclerosis) participants ≥65 years of age who had CAC = 0 at Visit 1 and a follow-up CAC scan. Multivariable adjusted Cox hazards ratios (aHR) and C-statistics were calculated to examine the association of nontraditional RF with incident CAC. ResultsThe mean age was 70.2 years and 67% were women. The median follow-up time to repeat CAC scan was 3.6 years (IQR: 2.6-9.2 years) and 45% of participants developed incident CAC. Albuminuria (aHR: 1.50, 95% CI: 1.07-2.09), carotid plaque (aHR: 1.32, 95% CI: 1.04-1.66), and thoracic aortic calcification (TAC) (aHR: 1.38, 95% CI: 1.10-1.75) were significantly associated with incident CAC, while higher levels of nontraditional RF including apolipoprotein-B, lipoprotein(a), high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide were not. When added to demographics, albuminuria, carotid plaque, and TAC provided a greater C-statistic improvement (+0.047, P = 0.004) vs all traditional RF combined (+0.033, P = 0.05). ConclusionsAmong nontraditional RF and measures of subclinical atherosclerosis, only albuminuria, carotid plaque, and TAC were significantly associated with incident CAC in persons ≥65 years of age. Identification of albuminuria or extracoronary atherosclerosis may help guide the timing of repeat CAC scoring in older persons with baseline CAC = 0.

Coronary artery calcium and the risk of cardiovascular events and mortality in younger adults: a meta-analysis.

American College of Cardiology/American Heart Association 2019 prevention guidelines recommend utilizing coronary artery calcium (CAC) to stratify cardiovascular risk in selected cases. However, data regarding CAC and risk in younger adults are less robust due to the lower prevalence of CAC and lower incidence of events. The objective of this meta-analysis is to determine the ability of CAC to predict the risk of cardiovascular events and mortality in adults <50. PubMed and Cochrane CENTRAL databases were electronically searched through May 2022 for studies with a primary prevention cohort under age 55 who underwent CAC scoring. Six observational studies with a total of 45 919 individuals with an average age of 43.1 and mean follow-up of 12.1 years were included. The presence of CAC was associated with an increased risk of adverse events [pooled hazard ratio (HR) = 1.80, 95% confidence interval (CI) 1.26-2.56, P = 0.012, I2 = 65.5]. Compared with a CAC of 0, a CAC of 1-100 did carry an increased risk of cardiovascular events (pooled HR = 1.85, 95% CI 1.08-3.16, P = 0.0248, I2 = 50.3), but not mortality (pooled HR = 1.20, 95% CI 0.85-1.69, P = 0.2917), while a CAC > 100 did carry an increased risk of cardiovascular events (pooled HR = 6.57, 95% CI 3.23-13.36, P < 0.0001, I2 = 72.6) and mortality (pooled HR = 2.91, 95% CI 2.23-3.80, P < 0.0001). In a meta-analysis of younger adults undergoing CAC scoring, a CAC of 1-100 was associated with a higher likelihood of cardiovascular events, while a CAC > 100 was associated with a higher likelihood of cardiovascular events and mortality.

Abstract 17639: Association of Retinal Microvascular Changes With Incidence and Progression of Coronary Artery Calcium Score in Individuals With vs Without Diabetes Mellitus; Data From the Multi-Ethnic Study of Atherosclerosis

Introduction: Retinopathy (RP) is a microvascular complication of diabetes mellitus (DM); however, it is also increasingly recognized in persons without DM. Microvascular disease may play a prominent role in coronary heart disease (CHD) development. We performed this study to evaluate the association of grades of RP with incidence of CAC (Coronary Artery Calcium) among those with zero CAC at baseline. Hypothesis: We performed this study to evaluate the association of grades of RP with incidence of CAC among those with zero CAC at baseline and to Identify the association of grades of MA and RP with progression of CAC among those with positive CAC at baseline. Methods: We included 5709 subjects with and without DM from the Multi-Ethnic Study of Atherosclerosis (MESA), who had retinal photos and CAC score available. We analyzed the association of grades of RP with incidence and progression of CAC among subjects with and without DM with zero CAC and positive CAC at baseline from robust regression models. The grades of RP were defined as: no retinopathy, minimal non-proliferative R (NPR) (level 14 -20), early to moderate NPR (level 31-41) and severe NPR or proliferative RP (level 51-80). Results: Among those with zero CAC, in the diabetic group, early to moderate (95% CI [1.2, 2]) and severe (95% CI [1.3, 3]) NPR had significantly higher incident CAC risk than the non-retinopathy group. Among those with positive CAC at baseline, in the diabetic group, the early to moderate NPR group had higher CAC progression than the non-retinopathy group. (95% CI [-146, 228]). In the non-diabetic group, the minimal NPR group had significantly higher CAC progression than the non-retinopathy group (95% CI [1.8, 52.7]). Conclusions: In conclusion, after adjustment for major CHD risk factors, RP with any severity was associated with incident CAC in DM individuals, however only early to moderate NPDR was associated with CAC progression in them.

Abstract 13657: Cholesterol Content of VLDL Particles and Incident Coronary Artery Calcification Among ELSA-Brasil Participants - A Metabolomic Approach

Background: Very-low density lipoproteins (VLDL) are the smallest and most atherogenic particles. Research question: The association of cholesterol content in VLDL particles with incident coronary artery calcification (CAC) is unclear. Aim: To analyze the association of VLDL cholesterol content with 5-year CAC status among ELSA-Brasil participants. Methods: Data from 832 participants (50.3±7.2 years, 50.4% women) free of cardiovascular disease and statin use were analyzed. The cholesterol content of VLDL lipoproteins were assessed by high-throughput proton Nuclear Magnetic Resonance metabolomics platform. CAC score was assessed by computed tomography at baseline and after 5-year follow-up, being classified as absent CAC (baseline and follow-up CAC=0), prevalent CAC (baseline CAC&gt;0) and incident CAC (baseline CAC=0 and follow-up CAC&gt;0). Distribution of cholesterol content were compared by U-Mann Whitney test according to CAC status. Generalized linear models compared cholesterol concentrations according to CAC status, adjusted by sociodemographic (age, sex, race, education, health insurance), lifestyle (physical activity, alcohol and smoking) and comorbidities (hypertension, diabetes, obesity and total cholesterol ≥200mg/dL). Results: CAC incident was 6.6% of sample (n=55), whereas 26.2% was CAC prevalent (n=218) and 67.2% was CAC absent (n=559). VLDL cholesterol concentrations in CAC incident participants were higher than those with CAC absent, but similar to those with CAC prevalent - Figure 1. Regression models showed higher concentrations of all lipids in CAC incident than CAC absent, but there was no difference between CAC incident and CAC prevalent. The associations remained beyond adjustment for sociodemographic and lifestyle factors, but lost significance after adjustment for comorbidities. Conclusions: This finding suggests a predictive role of VLDL cholesterol content for CAC incidence among ELSA-Brasil participants.

Abstract 15674: Association of Diastolic Blood Pressure and Coronary Artery Calcium Score in South Asian Adults: The MASALA Study

Background: Diastolic blood pressure (DBP) is associated with coronary artery calcium (CAC). Prior evaluation of this relationship has not included South Asian populations, who experience a disproportionate burden of cardiovascular disease. Hypothesis: High DBP is associated with CAC independent of systolic BP in South Asian adults. Methods: In the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study, we evaluated the cross-sectional association of sex-specific DBP quartiles and CAC≥100 with robust Poisson regression adjusted for age, sex, systolic BP, body mass index, smoking, low- and high-density lipoprotein cholesterol, triglycerides, diabetes, lipid-lowering and hypertension (HTN) medication use. Restricted cubic splines examined the continuous association of DBP with CAC probability. Secondary analysis examined the association between baseline DBP quartile and incident CAC over median 4.7 years of follow-up. Results: Among 1164 participants (48% female, mean age 57 years), mean (standard deviation) DBP was 74 (10) mmHg, 67% were not on HTN medications, 22% had CAC ≥100. The probability of CAC≥100 across levels of DBP is modeled in the Figure. DBP in quartiles 3 and 4 was significantly associated with CAC≥100 with adjusted prevalence ratio (PR, versus quartile 1) of 1.57 [95% CI, 1.20-2.06] and 1.50 [1.08-2.07], respectively. Among those not on HTN medication, the PR for CAC≥100 for DBP quartiles 3 and 4 was 1.98 [1.29-3.04] and 1.80 [1.00-3.24], respectively. Baseline DBP quartile was not associated with incident CAC, but those in quartile 4 had greater risk of CAC≥100 over follow-up compared to quartile 1 (RR 2.47, 1.17-5.23). Conclusion: Among South Asian adults in MASALA, having DBP in quartiles 3 or 4 was associated with a higher probability of CAC≥100. DBP may be an important clinical risk factor when assessing cardiovascular risk among South Asian adults.

Abstract 12124: GlycA is Associated With Both Coronary Artery Calcium Incidence and Progression: ELSA-Brasil Cohort Analysis

Introduction: GlycA is an emerging systemic inflammatory marker and quantifies N-acetyl glucosamine within the glycan region of acute phase proteins. Elevated levels of GlycA, are associated with a higher risk for coronary artery disease (CAD). There is conflicting evidence on whether GlycA levels can predict subclinical CAD progression in healthy adults. Hypothesis: High GlycA levels can predict subclinical CAD progression in healthy patients. Methods: We included 2,690 participants from the ELSA-Brasil cohort without cardiovascular/chronic inflammatory disease not receiving statin therapy who had GlycA level measured and two interval coronary artery calcium score (CAC) assessments between 2010 through 2018. Multivariable regression models adjusted for demographics, lifestyle, comorbidities, and laboratory parameters were used to assess the consistency of GlycA levels and CAC incidence and progression (Berry definition). CAC incidence required that the first CAC = 0. CAC progression required that the first CAC &gt; 0. Therefore, the presence of CAC incidence and progression were mutually exclusive. Results: The mean age of participants was 48.6 ± 7.7 years, 56.7% were female, 54.6% and 16.1% (429/2690) were White and Black, respectively. The mean CAC interscan period was 5.1 ± 0.9 years, the mean GlycA level was 414.7 ± 65 μmol/L, and the incidence of CAC was 13.1%. GlycA level odds ratio (OR) for CAC incidence was 1.002 (95% CI 1.0005-1.005, p = .016) adjusted for demographics, lifestyle, early (≤60 years) CAD family history, lipid panel, and comorbidities. The GlycA (≤p25 vs &gt;p75) OR for CAC progression (Berry definition) was 1.77 (95% CI 1.07-2.96, p = .03) in a similar multivariable adjustment model. Conclusions: Higher GlycA levels were associated with CAC incidence and progression even after adjusting for multivariable risk factors in a healthy Brazilian cohort. GlycA may have potential to further stratify CAD risk in healthy patients.

Association of apolipoproteins C-I and C-II truncations with coronary heart disease and progression of coronary artery calcium: Multi-Ethnic Study of Atherosclerosis

Background and aimsHigher truncated-to-native proteoform ratios of apolipoproteins (apo) C-I (C-I’/C-I) and C-II (C-II’/C-II) are associated with less atherogenic lipid profiles. We examined prospective relationships of C-I’/C-II and C-II’/C-II with coronary heart disease (CHD) and coronary artery calcium (CAC). MethodsApoC-I and apoC-II proteoforms were measured by mass spectrometry immunoassay in 5790 MESA baseline plasma samples. CHD events (myocardial infarction, resuscitated cardiac arrest, fatal CHD, n = 434) were evaluated for up to 17 years. CAC was measured 1–4 times over 10 years for incident CAC (if baseline CAC = 0), and changes (follow-up adjusted for baseline) in CAC score and density (if baseline CAC>0). ResultsC-II’/C-II was inversely associated with CHD (n = 434 events) after adjusting for non-lipid cardiovascular risk factors (Hazard ratio: 0.89 [95% CI: 0.81–0.98] per SD), however, the association was attenuated after further adjustment for HDL levels (0.93 [0.83–1.03]). There was no association between C-I’/C-I and CHD (0.98 [0.88–1.08]). C-II’/C-II was positively associated with changes in CAC score (3.4% [95%CI: 0.6, 6.3]) and density (6.3% [0.3, 4.2]), while C-I’/C-I was inversely associated with incident CAC (Risk ratio: 0.89 [95% CI: 0.81, 0.98]) in fully adjusted models that included plasma lipids. Total apoC-I and apoC-II concentrations were not associated with CHD, incident CAC or change in CAC score. ConclusionsIncreased apoC-II truncation was associated with reduced CHD, possibly explained by differences in lipid metabolism. Increased apoC-I and apoC-II truncations were also associated with less CAC progression and/or development of denser coronary plaques.