Incident Coronary Artery Calcification Research Articles

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 (> 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 < .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.

Risk Factors for Incident Coronary Artery Calcium in Younger (Age 32 to 45 Years) Versus Intermediate (46 to 64 Years) Versus Older (65 to 84 Years) Persons

The prognostic value of traditional atherosclerotic cardiovascular disease (ASCVD) risk factors may decrease with age. We sought to determine whether the association between traditional ASCVD risk factors and incident coronary artery calcium (CAC) differs for younger versus older persons. We included 5,108 participants with baseline CAC=0. Repeat CAC scoring occurred over 3 to 11 years of follow-up. Multivariable Cox proportional hazards regression assessed the association between traditional risk factors and incident CAC in young (32 to 45 years), middle-aged (46 to 64 years), and older adults (65 to 84 years). A total of 61% of the participants were women and 37% were Black. The proportion with incident CAC ranged from 22% among young adults, 34% for middle-aged adults, and 45% for older adults. In young adults, traditional risk factors were significantly associated with incident CAC except for diastolic blood pressure and high-density lipoprotein (HDL) cholesterol, whereas only total cholesterol/HDL cholesterol ≥3.5 (p=0.04) was significantly associated with incident CAC in older persons. Non-HDL cholesterol (p=0.02) was more strongly associated with incident CAC in young (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09 to 1.31) and middle aged (HR 1.14, 95% CI 1.07 to 1.23) compared to older adults (HR 1.11, 95% CI 0.99 to 1.23). When added to demographics, traditional risk factors provided a greater C-statistic improvement for incident CAC prediction in young (0.752, +0.070, p <0.001) versus middle-aged (0.645, +0.054, p <0.001) and older adults (0.597,+0.025, p=0.08). In conclusion, traditional risk factors more strongly predict incident CAC in young compared to older adults, underlining the importance of primordial prevention through middle age while identifying the challenges of ASCVD risk assessment in older persons.

Incremental prognostic value of triglyceride glucose index additional to coronary artery calcium score in asymptomatic low-risk population

BackgroundThe triglyceride glucose (TyG) index has been suggested as a reliable surrogate marker of insulin resistance which is a substantial risk factor for atherosclerotic cardiovascular disease (ASCVD). Several recent studies have shown the relationship between the TyG index and cardiovascular disease; however, the role of the TyG index in coronary artery calcification (CAC) progression has not been extensively assessed especially in low-risk population.MethodsWe enrolled 5775 Korean adults who had at least two CAC evaluations. We determined the TyG index using ln (fasting triglycerides [mg/dL] x fasting glucose [mg/dL]/2). The CAC progression was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥ 2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACSs) of subjects with detectable CAC at baseline.ResultsCAC progression was seen in 1,382 subjects (23.9%) during mean 3.5 years follow-up. Based on the TyG index, subjects were stratified into four groups. Follow-up CACS and incidence of CAC progression were markedly elevated with rising TyG index quartiles (group I [lowest]:17.6% vs. group II:22.2% vs. group III:24.6% vs. group IV [highest]: 31.3%, p < 0.001). In multivariate logistic regression analysis, the TyG index was independent predictor of CAC progression (odds ratio: 1.57; 95% confidence interval: 1.33 to 1.81; p < 0.001) especially in baseline CACS ≤ 100 group.ConclusionThe TyG index is an independent predictor of CAC progression in low-risk population. It adds incremental risk stratification over established factors including baseline CACS.

Association of Cardiovascular Health Through Young Adulthood With Genome-Wide DNA Methylation Patterns in Midlife: The CARDIA Study.

Cardiovascular health (CVH) from young adulthood is strongly associated with an individual's future risk of cardiovascular disease (CVD) and total mortality. Defining epigenomic biomarkers of lifelong CVH exposure and understanding their roles in CVD development may help develop preventive and therapeutic strategies for CVD. In 1085 CARDIA study (Coronary Artery Risk Development in Young Adults) participants, we defined a clinical cumulative CVH score that combines body mass index, blood pressure, total cholesterol, and fasting glucose measured longitudinally from young adulthood through middle age over 20 years (mean age, 25-45). Blood DNA methylation at >840 000 methylation markers was measured twice over 5 years (mean age, 40 and 45). Epigenome-wide association analyses on the cumulative CVH score were performed in CARDIA and compared in the FHS (Framingham Heart Study). We used penalized regression to build a methylation-based risk score to evaluate the risk of incident coronary artery calcification and clinical CVD events. We identified 45 methylation markers associated with cumulative CVH at false discovery rate <0.01 (P=4.7E-7-5.8E-17) in CARDIA and replicated in FHS. These associations were more pronounced with methylation measured at an older age. CPT1A, ABCG1, and SREBF1 appeared as the most prominent genes. The 45 methylation markers were mostly located in transcriptionally active chromatin and involved lipid metabolism, insulin secretion, and cytokine production pathways. Three methylation markers located in genes SARS1, SOCS3, and LINC-PINT statistically mediated 20.4% of the total effect between CVH and risk of incident coronary artery calcification. The methylation risk score added information and significantly (P=0.004) improved the discrimination capacity of coronary artery calcification status versus CVH score alone and showed association with risk of incident coronary artery calcification 5 to 10 years later independent of cumulative CVH score (odds ratio, 1.87; P=9.66E-09). The methylation risk score was also associated with incident clinical CVD in FHS (hazard ratio, 1.28; P=1.22E-05). Cumulative CVH from young adulthood contributes to midlife epigenetic programming over time. Our findings demonstrate the role of epigenetic markers in response to CVH changes and highlight the potential of epigenomic markers for precision CVD prevention, and earlier detection of subclinical CVD, as well.

Coronary artery calcium incidence and changes using direct plaque measurements: The MASALA study

Background and aimsWe aimed to identify predictors of change in direct measures of coronary artery calcium (CAC) volume and density in South Asian participants. MethodsWe used data from participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with prevalent CAC and direct measures of CAC by serial computed tomography (CT) exams (2010–2013, 2016–2018). We examined the distribution of incident CAC volume and peak density, as well as progression and identified risk factors for progression of change in volume and density in multivariable models. ResultsThe study cohort consisted of 102 participants with incident CAC and 285 with CAC progression. CAC volume and density were highest, and incident CAC was most common in the left anterior descending artery (LAD). The greatest progression in volume was in the right coronary artery and the greatest change in density was in the left main. In linear regression models for CAC progression adjusted for baseline density, volume, risk factors, smoking (β +190.1, p = 0.02), baseline volume (β +0.24 per mm3, p < 0.01), and scan interval (β +0.15 per day, p = 0.01) were associated with change in total volume whereas Lp(a) (β +0.81 per mg/dL, p = 0.03), exercise (β +0.19 per 10 MET-min/week, p = 0.01), and baseline volume (β +0.15 per mm3, p < 0.01) and density (β −0.55 per unit, p < 0.01) were associated with change in total density. ConclusionsIn this South Asian cohort, smoking was associated with CAC volume progression, while Lp(a) and exercise were associated with progression of peak CAC density.

Deoxycholic Acid and Coronary Artery Calcification in the Chronic Renal Insufficiency Cohort.

BackgroundDeoxycholic acid (DCA) is a secondary bile acid that may promote vascular calcification in experimental settings. Higher DCA levels were associated with prevalent coronary artery calcification (CAC) in a small group of individuals with advanced chronic kidney disease. Whether DCA levels are associated with CAC prevalence, incidence, and progression in a large and diverse population of individuals with chronic kidney disease stages 2 to 4 is unknown.Methods and ResultsIn the CRIC (Chronic Renal Insufficiency Cohort) study, we evaluated cross‐sectional (n=1057) and longitudinal (n=672) associations between fasting serum DCA levels and computed tomographic CAC using multivariable‐adjusted regression models. The mean age was 57±12 years, 47% were women, and 41% were Black. At baseline, 64% had CAC (CAC score >0 Agatston units). In cross‐sectional analyses, models adjusted for demographics and clinical factors showed no association between DCA levels and CAC >0 compared with no CAC (prevalence ratio per 1‐SD higher log DCA, 1.08 [95% CI, 0.91–1.26). DCA was not associated with incident CAC (incidence per 1‐SD greater log DCA, 1.08 [95% CI, 0.85–1.39]) or CAC progression (risk for increase in ≥100 and ≥200 Agatston units per year per 1‐SD greater log DCA, 1.05 [95% CI, 0.84–1.31] and 1.26 [95% CI, 0.77–2.06], respectively).ConclusionsAmong CRIC study participants, DCA was not associated with prevalent, incident, or progression of CAC.

Comprehensive Meta-Analysis of Functional and Structural Markers of Subclinical Atherosclerosis in Women with Polycystic Ovary Syndrome.

The relationship between polycystic ovary syndrome (PCOS) and subclinical atherosclerosis remains unclear. We performed a comprehensive systematic review and meta-analysis to evaluate the effect of PCOS on functional and structural markers of subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT), flow-mediated vasodilation (FMD), nitroglycerin-mediated vasodilation (NMD), pulse wave velocity (PWV), and coronary artery calcium (CAC). Standard mean differences (SMDs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Ninety-six articles involving 5550 PCOS patients and 5974 controls were included. Compared with controls, PCOS patients showed significantly thicker cIMT (SMD (95% CI) = .587 (.398, .776), P < .001), lower FMD (SMD (95% CI) = -.649 (-.946, -.353), P < .001) and NMD (SMD (95% CI) = -.502 (-.686, -.317), P < .001), as well as higher PWV (SMD (95% CI) = .382 (.019, .746), P = .039), and increased CAC incidence (OR (95% CI) = 2.204 (1.687, 2.879), P < .001). When analyzing subgroups by age and body mass index (BMI), results were still significant (P < .05) except for PWV in the BMI subgroup. There was no significant result on sensitivity analysis, and Begg' test or Egger's test. PCOS contributes to subclinical atherosclerosis, resulting in functional and structural changes in cIMT, FMD and NMD, PWV, and CAC incidence.

Exposure to Neighborhood-Level Racial Residential Segregation in Young Adulthood to Midlife and Incident Subclinical Atherosclerosis in Black Adults: The Coronary Artery Risk Development in Young Adults Study.

Neighborhood-level racial residential segregation has been linked to several cardiovascular disease risk factors and outcomes in Black adults, but its impact on subclinical atherosclerosis remains unknown. In addition, although the impact of segregation on health may vary over the life course, most studies have examined segregation exposure at a single point in time. This article takes a life course approach by examining associations of exposure to neighborhood-level racial residential segregation in young adulthood and patterns of exposure from young adulthood to midlife with coronary artery calcification (CAC) incidence. We used data on 1125 Black CARDIA study (Coronary Artery Risk Development in Young Adults) participants free of CAC. Residential segregation was assessed using the Gi* statistic and measured when participants were young adults (18-30 years old, in 1985-1986) and as the pattern from young adulthood to midlife (15 years later). Poisson regression with generalized estimating equations models was used to measure CAC incidence. We found participants living in low segregation neighborhoods in young adulthood had 0.52 (rate ratio [95% CI: 0.28-0.98]) times lower risk of developing CAC compared with high segregation after adjusting for young adulthood sociodemographic characteristics and neighborhood poverty. Associations were attenuated and no longer statistically significant with adjustment for midlife CAC risk factors hypothesized to be on the causal pathway (rate ratio: 0.56 [95% CI: 0.29-1.09]). Findings for patterns of segregation over time suggest participants living in low segregation neighborhoods in young adulthood were less likely to develop CAC than those who started out in medium/high segregation neighborhoods, regardless of where they lived in midlife (rate ratio for increase from low to medium/high: 0.42 [95% CI: 0.19-0.95]; rate ratio for continuously low versus continuously medium/high segregation neighborhoods: 0.75 [95% CI: 0.31-1.83]). We found that participants living in more segregated neighborhoods in young adulthood were more likely to develop CAC due at least in part to differences in CAC risk factor burden accumulated over follow-up.

Metabolomic Analysis of Coronary Heart Disease in an African American Cohort From the Jackson Heart Study

African American individuals have disproportionate rates of coronary heart disease (CHD) but lower levels of coronary artery calcium (CAC), a marker of subclinical CHD, than non-Hispanic White individuals. African American individuals may have distinct metabolite profiles associated with incident CHD risk compared with non-Hispanic White individuals, and examination of these differences could highlight important processes that differ between them. To identify novel biomarkers of incident CHD and CAC among African American individuals and to replicate incident CHD findings in a multiethnic cohort. This analysis targeted plasma metabolomic profiling of 2346 participants in the Jackson Heart Study (JHS), a prospective population-based cohort study that included 5306 African American participants who were examined at baseline (2000-2004) and 2 follow-up visits. Replication of CHD-associated metabolites was sought among 1588 multiethnic participants from the Women's Health Initiative (WHI), a prospective population-based multiethnic cohort study of 161 808 postmenopausal women who were examined at baseline (1991-1995) and ongoing follow-up visits. Regression analyses were performed for each metabolite to examine the associations with incident CHD and CAC scores. Data were collected from the WHI between 1994 and 2009 and from the JHS between 2000 and 2015. All data were analyzed from November 2020 to August 2021. Plasma metabolites. Incident CHD was defined as definite or probable myocardial infarction or definite fatal CHD in both the JHS and WHI cohorts. In the JHS cohort, silent myocardial infarction between examinations (as determined by electrocardiography) and coronary revascularization were included in the incident CHD analysis. Coronary artery calcium was measured using a 16-channel computed tomographic system and reported as an Agatston score. Among 2346 African American individuals in the JHS cohort, the mean (SD) age was 56 (13) years, and 1468 individuals (62.6%) were female. Among 1588 postmenopausal women in the WHI cohort, the mean (SD) age was 67 (7) years; 217 individuals (13.7%) self-identified as African American, 1219 (76.8%) as non-Hispanic White, and 152 (9.6%) as other races or ethnicities. In the fully adjusted model including 1876 individuals, 46 of 303 targeted metabolites were associated with incident CHD (false discovery rate q <0.100). Data for 32 of the 46 metabolites were available in the WHI cohort, and 13 incident CHD-associated metabolites from the JHS cohort were replicated in the WHI cohort. A total of 1439 participants from the JHS cohort with available CAC scores received metabolomic profiling. Nine metabolites were associated with CAC scores. Minimal overlap was found between the results from the incident CHD and CAC analyses, with only 3 metabolites shared between the 2 analyses. This cohort study identified metabolites that were associated with incident CHD among African American individuals, including 13 incident CHD-associated metabolites that were replicated in a multiethnic population and 9 novel metabolites that included N-acylamides, leucine, and lipid species. These findings may help to elucidate common and distinct metabolic processes that may be associated with CHD among individuals with different self-identified race.

Abstract 9187: Risk Factors for the Onset of Coronary Artery Calcium in Younger versus Older Persons

Introduction: Modifiable traditional atherosclerotic cardiovascular disease (ASCVD) risk factors (RFs) have a decreased predictive strength with higher ages. Whether the strength of relationship between these RFs and incident coronary artery calcium (CAC) changes with age is unknown. Hypothesis: Modifiable traditional ASCVD RFs will have a weaker association with incident CAC in older versus young adults. Methods: There were 5108 CARDIA and MESA participants without clinical ASCVD and baseline CAC=0. Repeat CAC scoring occurred 10 years later in CARDIA and 3-11 years later in MESA. Multivariable Cox proportional hazards regression calculated hazard ratios and C-statistics for RFs with incident CAC in young (32-45 years), middle-aged (46-64 years) and older adults (65-84 years). Results: A total of 61% of adults were women and 37% were African American. The proportion with incident CAC increased from young (22%) to middle-aged (33%) and older adults (45%). All modifiable traditional RFs were significantly associated with incident CAC except for diastolic blood pressure and HDL-C in young adults, whereas among older adults only a total cholesterol/HDL-C &gt; 3.5 (p=0.04) was significantly associated with incident CAC. Systolic blood pressure was the modifiable RF with the strongest association per 1 standard deviation change for incident CAC in young adults (HR=1.29, 95% CI: 1.13-1.48), conferring lower risks in middle-aged (HR=1.20, 95% CI: 1.06-1.36) and older adults (HR=1.10, 95% CI: 0.96-1.27). Modifiable traditional RFs provided a greater improvement in the C-statistic for incident CAC prediction in young versus middle-aged and older adults ( Table ). Conclusion: Modifiable traditional ASCVD RFs were stronger predictors of incident CAC for young compared to older adults, which may be due to their higher prevalence with increasing age. Further research is needed to examine whether nontraditional RFs improve incident CAC prediction in adults &gt; 65 years old.

Abstract 9962: Associations of Prepregnancy Cardiovascular Health and Adverse Pregnancy Outcomes with Incident Coronary Artery Calcium During Midlife: A Mediation Analysis in the Coronary Artery Risk Development in Young Adults Study

Introduction: Adverse pregnancy outcomes (APOs) are emerging as critical risk markers for the development of cardiovascular disease (CVD). Risk of APOs are higher among women with worse prepregnancy cardiovascular health (CVH), but it remains unclear if APOs mediate the relationship between prepregnancy CVH and incident coronary artery calcium (CAC). Methods: We included individuals in the Coronary Artery Risk Development in Young Adults study with at least one singleton birth prior to 2001 and data on prepregnancy CVH (1985-1996) and CAC (2000-2011). Data on APOs were self-reported at each visit (gestational diabetes, hypertensive disorders of pregnancy, preterm birth and small for gestational age). We quantified prepregnancy CVH by summing across the American Heart Association’s Life’s Simple 7 (score 0-14). We used Cox proportional hazards models to obtain hazard ratios (HRs) for a one-point higher (better) prepregnancy CVH score for incident CAC (CAC &gt; 0) adjusted for age, self-reported race, education (years) and parity. We used causal mediation analyses to estimate the proportion of the association between prepregnancy CVH and incident CAC mediated through any APO and each APO subtype. Results: Of the 906 included participants, 46.1% were Black, mean age ± SD was 28.1 ± 4.5 years at baseline and 43.0 ± 4.8 years at follow-up. Among individuals with low (0-7), intermediate (8-11) and high (12-14) prepregnancy CVH, APOs developed in 41.8%, 29.5% and 19.5% respectively, and CAC developed in 38.8%, 14.8% and 11.6% of women, respectively. Adjusted HR (95% CI) for one-point higher (better) prepregnancy CVH on incident CAC was 0.79 (0.72, 0.87). APOs did not significantly mediate the relationship between prepregnancy CVH and CAC ( TABLE ). Conclusions: Higher or more favorable prepregnancy CVH is associated with lower risk of subclinical CVD in midlife, regardless of APO status, and highlights the importance optimizing CVH early in the life course prior to pregnancy.

Abstract 9867: Associations of Urinary Isoprostane Levels with Prevalence and Progression of Coronary Artery Calcification and Carotid Plaque in the Multi-Ethnic Study of Atherosclerosis (mesa)

Introduction: Urinary isoprostanes reflect oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC) &amp; carotid plaque are markers of subclinical atherosclerosis and prognostic of ASCVD risk. We examined if the urinary isoprostane iPF2α-III and its metabolite iPF2α-III-M were associated with CAC &amp; carotid plaque. Hypothesis: Higher urinary isoprostanes are associated with a greater prevalence, incidence, burden, and progression of CAC &amp; carotid plaque. Methods: 1097 MESA participants free of ASCVD had urinary isoprostanes measured at baseline. All participants underwent cardiac CT at baseline; 1083 underwent repeat CT ~10 yrs later. CAC was measured by Agatston scoring. All participants had carotid ultrasound (US) at baseline; 837 underwent repeat carotid US ~10 yrs later. Carotid plaque score (CPS) was defined as the number of carotid segments containing plaque. Isoprostane levels were divided into tertiles. Relative risk regression and linear mixed effect models determined prevalence/incidence and burden/progression respectively of CAC &amp; CPS. Results: Mean age of participants at baseline was 62.2 (8.3) yrs; 49% were women. There was no association of isoprostanes with CAC at baseline. There was a positive, but not statistically significant association, comparing the highest vs lowest tertiles of iPF2α-III-M and CAC progression over 10 yrs (Fig 1a). There was a statistically significant association comparing the highest vs lowest tertiles of isoprostanes with prevalence and burden of carotid plaque at baseline, but not with CPS incidence/progression (Fig 1b). Conclusions: In this multiethnic cohort, urinary isoprostanes were weakly but positively associated with carotid plaque burden and prevalence in cross sectional analysis and also showed a non-significant trend toward CAC progression, suggesting this measure of oxidative stress may be associated with ASCVD.

Association of inflammatory markers and lipoprotein particle subclasses with progression of coronary artery calcium: The multi-ethnic study of atherosclerosis

Background and aimsAtherosclerosis is a complex phenomenon manifesting several features typical of chronic inflammation and disorders of lipid metabolism. We assessed association of nuclear magnetic resonance (NMR) lipid variables and inflammatory markers with incident coronary artery calcium (CAC) and CAC progression among participants with baseline CAC ≥0. MethodsMESA is a longitudinal cohort study of 6,814 participants (aged 45–85). 3,115 had CAC = 0 and 2,896 had CAC>0 at baseline. Repeat CAC measurements were obtained (mean duration of follow up, 6.5 years). ResultsIL-6 (log pg/mL) and fibrinogen (50 mg/dL) were associated with a higher relative risk (RR) of incident CAC (HU) (RR = 1.09, p=0.010 & RR 1.05, p=0.004, respectively). Small LDL (100 nmol/L) (RR = 1.03, p<0.001) and log large VLDL (log nmol/L) (RR = 1.06, p=0.001) were associated with higher risks, whereas large HDL (μmol/L) was associated with an inverse risk of incident CAC (RR = 0.97, p< 0.001) in a model adjusted for follow up time, age, gender and race. Among participants with baseline CAC>0, progression of CAC was positively associated with hsCRP (log mg/L) (β = 1.99), IL-6 (log pg/mL) (β = 2.9), fibrinogen (50 mg/dL) (β = 1.0), large VLDL (log nmol/L) (β = 2.2), and small LDL (100 nmol/L) (β = 0.36) (all p values < 0.05) in a model adjusted for scanner type, age, gender and race. Relationships with inflammatory markers and NMR lipoprotein particles lost significance after adjustment for traditional risk factors and statin use. Traditional risk factors were strongly associated with both CAC incidence and progression with the exception of cholesterol parameters not associated with CAC progression in adjusted model. ConclusionsInflammatory markers and lipoprotein particles were associated with CAC incidence and progression in minimally adjusted models, but not after adjustment for traditional risk factors.