Incident Coronary Artery Calcification Research Articles

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 & 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 >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 a cardiovascular events and mortality in younger adults: a meta-analysis.

ACC/AHA 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 is 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 less than 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 to 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.

Predictive value of lipoprotein(a) in coronary artery calcification among asymptomatic cardiovascular disease subjects: A systematic review and meta-analysis

AimsStudies have indicated inconsistent results regarding the association between plasma levels of Lipoprotein(a) [Lp(a)] and coronary artery calcification (CAC). We performed a systematic review and meta-analysis to investigate the association between elevated levels of Lp(a) and risk of CAC in populations free of cardiovascular disease (CVD) symptoms. Data synthesisPubMed, Web of Science, Embase, and Scopus were searched up to July 2022 and the methodological quality was assessed using Newcastle–Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratio (OR) and 95% confidence interval. Out of 298 studies, data from 8 cross-sectional (n = 18,668) and 4 cohort (n = 15,355) studies were used in meta-analysis. Cohort studies demonstrated a positive significant association between Lp(a) and CAC, so that individuals with Lp(a)≥30–50 exposed to about 60% risk of CAC incidence compared to those with lower Lp(a) concentrations in asymptomatic CVD subjects (OR, 1.58; 95% CI, 1.38–1.80; l2, 0.0%; P, 0.483); Subgroup analysis showed that a cut-off level for Lp(a) measurement could not statistically affect the association, but race significantly affected the relationship between Lp(a) and CAC (OR,1.60; 95% CI, 1.41–1.81). Analyses also revealed that both men and women with higher Lp(a) concentrations are at the same risk for increased CAC. ConclusionsBlood Lp(a) level was significantly associated with CAC incidence in asymptomatic populations with CVD, indicating that measuring Lp(a) may be a useful biomarker for diagnosing subclinical atherosclerosis in individuals at higher risk of CAC score. Prospero registration numberCRD42022350297.

Long-Term High Level of Insulin Resistance Is Associated With an Increased Prevalence of Coronary Artery Calcification: The CARDIA Study.

Background Coronary artery calcification (CAC) is a crucial indicator of subclinical atherosclerotic cardiovascular disease. The relationship between long-term insulin resistance (IR) trajectory and CAC has been explored in few studies. Therefore, this study aimed to investigate whether the long-term IR time series of young adults are associated with the incidence of CAC in midlife. Methods and Results In a cohort study comprising 2777 participants from the CARDIA (Coronary Artery Risk Development in Young Adults) study, the homeostasis model assessment for IR was used to measure IR levels, and group-based trajectory modeling was used to fit three 25-year homeostasis model assessments for IR trajectories. Logistic regression was used to estimate the association between the 3 homeostasis model assessments for IR trajectories and CAC events at year 25. The results showed that among 2777 participants (mean age, 50.10±3.58 years; 56.2% women; 46.4% Black), there were 780 incident CAC events after a 25-year follow-up. After full adjustment, the prevalence of CAC was higher in the moderate- (odds ratio [OR], 1.40 [1.10-1.76]) and the high-level homeostasis model assessments for IR trajectories (OR, 1.84 [1.21-2.78]) than in the low-level trajectory. This association was observed in obese individuals despite the negative interaction between IR and different types of obesity (all P interactions >0.05). Conclusions Our study revealed that young adults with a higher level of IR were more likely to develop CAC in middle age. Furthermore, this association persisted in obese individuals. These findings highlight the importance of identifying subclinical cardiovascular risk factors and implementing primary prevention measures.

Abstract MP67: The Relationship of Cardiorespiratory Fitness, Physical Activity, and Coronary Artery Calcification to Incident Cardiovascular Disease Events in Cardia Participants

Introduction: Coronary artery calcification (CAC) score, physical activity (PA), and cardiorespiratory fitness (CRF) are all associated with cardiovascular disease (CVD) risk. While a U-shaped relationship between PA and CRF with CAC has been reported, CAC presence among highly fit individuals was suggested to be benign. Objective: To determine interactive associations of PA/CRF and CAC with outcomes in a cohort of middle-aged adults and to evaluate the relationship of PA/CRF with CAC incidence. Methods: CARDIA participants with CT-assessed CAC at year 20 (2005-06) were included (n=3141, mean age 45y, 57% female, 45% Black). Moderate to vigorous intensity PA (MVPA) was assessed by self-report and accelerometer. CRF was estimated with a treadmill test. Incident CVD events were adjudicated, and mortality data were obtained through 2019. CAC was reassessed at year 25 (2010-11). Cox models assessed hazard ratios (HRs) for CVD and mortality in groups defined by CAC and MVPA/CRF. Logistic models assessed associations with CAC incidence. Results: At baseline, more favorable CVD risk was found among participants with higher MVPA, higher CRF (&gt; median sex-specific duration), and absence of CAC. During a mean follow-up of 13 years, 166 CVD events and 171 deaths occurred. After multivariable adjustment, compared with no CAC and higher CRF (ref), the HRs (95% CIs) for CVD were 5.04 (2.49-10.20) for CAC and higher CRF, 2.26 (1.24-4.12) for no CAC and lower CRF, and 4.27 (2.24-8.14) for CAC and lower CRF (Figure, left panel). The respective HRs for mortality were 1.12 (0.45-2.77), 1.54 (0.91-2.60), and 3.23 (1.82-5.72) (Figure, right panel). Similar findings were observed with self-reported or accelerometer MVPA replacing CRF. Higher CRF and accelerometer MVPA were dose-responsively associated with a lower probability of developing CAC in a 5-year follow-up (P &lt; .01). Conclusions: PA and CRF were inversely associated with CAC incidence in middle-aged adults. CAC presence eliminated the cardiovascular risk advantage of high PA or high CRF.

Comparative Associations of Nonalcoholic Fatty Liver Disease and Metabolic Dysfunction-Associated Fatty Liver Disease With Coronary Artery Calcification: A Cross-Sectional and Longitudinal Cohort Study.

In cross-sectional and retrospective cohort studies, we examined comparative associations between nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) and risk of having or developing coronary artery calcification (CAC). Participants who had health examinations between 2010 and 2019 were analyzed. Liver ultrasonography and coronary artery computed tomography were used to diagnose fatty liver and CAC. Participants were divided into a MAFLD and no-MAFLD group and then NAFLD and no-NAFLD groups. Participants were further divided into no fatty liver disease (reference), NAFLD-only, MAFLD-only, and both NAFLD and MAFLD groups. Logistic regression modeling was performed. Cox proportional hazard model was used to examine the risk of incident CAC in participants without CAC at baseline and who had at least two CAC measurements. In cross-sectional analyses, 162 180 participants were included. Compared with either the no-NAFLD or no-MAFLD groups, the NAFLD and MAFLD groups were associated with a higher risk of prevalent CAC (NAFLD: adjusted odds ratio [OR], 1.34 [95% CI, 1.29-1.39]; MAFLD: adjusted OR, 1.44 [95% CI, 1.39-1.48]). Among the 4 groups, the MAFLD-only group had the strongest association with risk of prevalent CAC (adjusted OR, 1.60 [95% CI, 1.52-1.69]). Conversely, the NAFLD-only group was associated with a lower risk of prevalent CAC (adjusted OR, 0.76 [95% CI, 0.66-0.87]). In longitudinal analyses, 34 233 participants were included. Compared with either the no-NAFLD or no-MAFLD groups, the NAFLD and MAFLD groups were associated with a higher risk of incident CAC (NAFLD: adjusted hazard ratio, 1.68 [95% CI, 1.43-1.99]; MAFLD: adjusted hazard ratio, 1.82 [95% CI, 1.56-2.13]). Among these 4 groups, the MAFLD-only group had the strongest associations with risk of incident CAC (adjusted hazard ratio, 2.03,[95% CI, 1.62-2.55]). The NAFLD-only group was not independently associated with risk of incident CAC (adjusted hazard ratio, 0.88 [95% CI, 0.44-1.78]) Conclusions: Both NAFLD and MAFLD are significantly associated with an increased prevalence and incidence of CAC. These associations tended to be stronger for MAFLD.

Cardiovascular risk-enhancing factors and coronary artery calcium in South Asian American adults: The MASALA study

ObjectivesThe 2018 and 2019 U.S. guidelines for the management of cholesterol and primary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend consideration of cardiovascular risk-enhancing factors (REFs), including South Asian ancestry, to refine ASCVD risk estimation. However, the associations of REFs with atherosclerosis are unclear in South Asian American adults, who have a disproportionately elevated premature coronary heart disease risk. In the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort, we investigated associations of individual REFs, or the number of REFs, with coronary artery calcium (CAC). MethodsUsing baseline and follow-up data from MASALA, we evaluated the association of REFs (family history of ASCVD, low-density lipoprotein cholesterol ≥160 mg/dL, triglycerides ≥175 mg/dL, lipoprotein(a) >50 mg/dL, high-sensitivity C-reactive protein [hsCRP] ≥2.0 mg/dL, ankle-brachial index <0.9, chronic kidney disease, metabolic syndrome), individually and combined, with baseline prevalent CAC, any CAC progression (including incident CAC and CAC progression), and annual CAC progression rates using multivariable logistic regression and generalized linear models. ResultsAmong 866 adults, mean age was 55 [SD 9] years and 47% were female. There were no significant associations of REFs with baseline prevalent CAC or any CAC progression (incident CAC and CAC progression at Exam 2) after adjustment. Among the 56% of participants who had any CAC progression, having 3+ REFs was associated with a significantly higher annual CAC progression rate (adjusted rate ratio [aRR] 1.94, 95% CI 1.39–2.72) vs. having 0 REFs. The annual CAC progression rate was 20% higher per additional REF (aRR 1.20, 95% CI 1.09–1.32). Findings were similar after excluding statin users, and among those with low 10-year ASCVD risk (<5%). ConclusionsAmong South Asian American adults, we found no association of REFs with prevalent CAC at baseline or having any CAC progression. Among those with any CAC progression, a higher number of REFs was associated with higher annual CAC progression rates.

Association of Vitamin K Status with Arterial Calcification and Stiffness in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort

BackgroundArterial calcification and stiffness are common in people with chronic kidney disease (CKD). Higher vitamin K status has been associated with less arterial calcification and stiffness in CKD in cross-sectional studies. ObjectivesTo determine the association of vitamin K status with coronary artery calcium (CAC) and arterial stiffness [pulse wave velocity (PWV)] at baseline and over 2–4 follow-up years in adults with mild-to-moderate CKD. MethodsParticipants (n = 2722) were drawn from the well-characterized Chronic Renal Insufficiency Cohort. Two vitamin K status biomarkers, plasma phylloquinone and plasma dephospho-uncarboxylated matrix gla protein [(dp)ucMGP], were measured at baseline. CAC and PWV were measured at baseline and over 2–4 y of follow-up. Differences across vitamin K status categories in CAC prevalence, incidence, and progression (defined as ≥100 Agatston units/y increase) and PWV at baseline and over follow-up were evaluated using multivariable-adjusted generalized linear models. ResultsCAC prevalence, incidence, and progression did not differ across plasma phylloquinone categories. Moreover, CAC prevalence and incidence did not differ according to plasma (dp)ucMGP concentration. Compared with participants with the highest (dp)ucMGP (≥450 pmol/L), those in the middle category (300–449 pmol/L) had a 49% lower rate of CAC progression (incidence rate ratio: 0.51; 95% CI: 0.33, 0.78). However, CAC progression did not differ between those with the lowest (<300 pmol/L) and those with the highest plasma (dp)ucMGP concentration (incidence rate ratio: 0.82; 95% CI: 0.56, 1.19). Neither vitamin K status biomarker was associated with PWV at baseline or longitudinally. ConclusionsVitamin K status was not consistently associated with CAC or PWV in adults with mild-to-moderate CKD.

Abstract 9978: Non-Traditional Risk Markers for Incident Coronary Artery Calcium Among Persons ≥65 Years Old: The Multi-Ethnic Study of Atherosclerosis

Introduction: Initiation of coronary artery calcium (CAC) is an important milestone associated with a marked increase in cardiovascular disease (CVD) risk. However, traditional risk factors do not perform well for CVD risk stratification among older persons. Hypothesis: Contrasting to measures of subclinical CVD, blood-based non-traditional risk factors will not strongly predict incident CAC in older adults. Methods: There were 815 participants &gt; 65 years old with CAC=0 at Visit 1. We calculated multivariable Cox hazards ratios and C-statistics for the association of non-traditional risk factors with incident CAC. Results: The mean age was 70.2 years old, 67% were women, and 35% were Black. A total of 55% developed incident CAC with a median follow-up time to incident CAC of 3.6 years. The largest proportion of persons with incident CAC was among those with microalbuminuria (Figure). Albuminuria (aHR=1.54, 95% CI: 1.10-2.16) and thoracic calcification (TAC) (aHR=1.38, 95% CI: 1.10-1.75) were significantly associated with incident CAC, while 1-SD higher level of apolipoprotein-B, lipoprotein(a), high-sensitivity troponin T, N-terminal pro-brain natriuretic peptide and C-reactive protein were not. When added to demographic information, albuminuria and TAC provided a greater C-statistic improvement (+0.044, p=0.01) versus all traditional risk factors combined (+0.029, p=0.09). Conclusions: Among non-traditional risk factors and measures of subclinical CVD, only albuminuria and TAC were significantly associated with incident CAC in persons &gt;65 years old. Identification of older persons with albuminuria or TAC may help guide the utility and timing of repeat CAC scoring in older persons with baseline CAC=0.

Dietary patterns and subclinical atherosclerosis incidence and progression: Results from ELSA-Brasil

Background and aimsCardiovascular disease (CVD) is the main cause of disease burden worldwide. Coronary artery calcification (CAC) score is a subclinical atherosclerosis marker able to predict the risk of CVD in asymptomatic patients, and few studies have investigated the association between dietary patterns (DP) and CAC score prospectively. Thus, the aim of this study was to estimate the association between baseline DP and CAC score incidence and progression on the ELSA-Brasil cohort. Methods and resultsThis study is a longitudinal prospective analysis of the ELSA-Brasil participants who underwent a CAC exam on baseline and follow-up (n = 2,824). CAC incidence was defined as a baseline CAC score equal to zero (n = 2,131) and subsequent follow-up CAC score greater than zero. CAC progression was defined according to the Hokanson method for the individuals who presented a CAC score greater than zero at the baseline (n = 639). Dietary data were assessed at the baseline using a food frequency questionnaire (FFQ), and factor analysis was applied to identify DP. Poisson regression models with robust variance and linear regression models were applied to estimate the association between baseline DP and CAC incidence and progression. The incidence of CAC was 14.6%, while 60.3% of the individuals presented CAC progression. Three DP were identified: convenience, Brazilian traditional, and prudent. We did not find a significant association between baseline DP and CAC incidence or progression. ConclusionOur findings from this longitudinal prospective analysis showed that baseline DP are not associated with CAC incidence or progression.