Coronary Artery Calcium Measurements Research Articles

Physical Activity and Progression of Coronary Artery Calcification in Men and Women.

Prior cross-sectional studies have suggested that very high levels of physical activity (PA) are associated with a higher prevalence of coronary artery calcium (CAC). However, less is known regarding the association between high-volume PA and progression of CAC over time. To explore the association between PA (measured at baseline and during follow-up) and the progression of CAC over time. This cohort study included data from 8771 apparently healthy men and women 40 years and older who had multiple preventive medicine visits at the Cooper Clinic (Dallas, Texas), with a mean (SD) follow-up time of 7.8 (4.7) years between the first and last clinic visit. Participants with reported PA and CAC measurements at each visit during 1998 to 2019 were included in the study. Data were analyzed from March 2023 to February 2024. PA reported at baseline and follow-up, examined continuously per 500 metabolic equivalent of task minutes per week (MET-min/wk) and categorically: less than 1500, 1500 to 2999, 3000 or more MET-min/wk. Negative binomial regression was used to estimate the rate of mean CAC progression between visits, with potential modification by PA volume, calculated as the mean of PA at baseline and follow-up. In addition, proportional hazards regression was used to estimate hazard ratios for baseline PA as a predictor of CAC progression to 100 or more Agatston units (AU). Among 8771 participants, the mean (SD) age at baseline was 50.2 (7.3) years for men and 51.1 (7.3) years for women. The rate of mean CAC progression per year from baseline was 28.5% in men and 32.1% in women, independent of mean PA during the same time period. That is, the difference in the rate of CAC progression per year was 0.0% per 500 MET-min/wk for men and women (men: 95% CI, -0.1% to 0.1%; women: 95% CI, -0.4% to 0.5%). Moreover, baseline PA was not associated with CAC progression to a clinically meaningful threshold of 100 AU or more over the follow-up period. The hazard ratio for a baseline PA value of 3000 or more MET-min/wk vs less than 1500 MET-min/wk to cross this threshold was 0.84 (95% CI, 0.66 to 1.08) in men and 1.16 (95% CI, 0.57 to 2.35) in women. This study found that PA volume was not associated with progression of CAC in a large cohort of healthy men and women who were initially free of overt cardiovascular disease.

Longitudinal associations of the alternative healthy eating index with coronary artery calcification and pericardial adiposity in US adults with and without type 1 diabetes

Background and aimLong-term associations between the alternative healthy eating index (AHEI) score and two predictive indicators for CVD, pericardial adipose tissue (PAT) and coronary artery calcification (CAC) volume, are lacking. Our study aims to investigate the longitudinal associations of the AHEI score with measures of CAC and PAT in adults with and without type 1 diabetes (T1D). Methods and resultsThe prospective Coronary Artery Calcification in T1D (CACTI) study included 652 people with T1D and 764 people without diabetes (non-DM) (19–56 years old) and was conducted in 2000–2002, 2003–2004, and 2006–2007. At each visit, food frequency questionnaires were collected and PAT and CAC were measured using electron beam computed tomography. Two variables were used for CAC analyses: a continuous variable for the square-root tranformed volume (SRV) for each visit and a second variable identified CAC progression from baseline to visit 3. Mixed effect models and a logistic regression model were used to conduct statistical analyses. A one-point increase in the AHEI score was significantly associated with a −0.12 cm3 (95% CI: −0.17, −0.08; p-value<0.0001) decrease in PAT volume in combined analyses, a −0.16 cm3 (95% CI: −0.22, −0.09; p-value<0.0001) decrease in the non-DM group, a marginally significant −0.07 cm3 (95% CI: −0.14, 0.002; p-value = 0.0571) decrease in the T1D group, and was not associated with either CAC outcome. ConclusionThe AHEI score is inversely associated with PAT; the association revealed greater magnitude of PAT reduction in the non-DM group. The AHEI score did not associate with CAC progression.

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.

Association between BMD and coronary artery calcification: an observational and Mendelian randomization study.

Observational studies have reported inconsistent associations between bone mineral density (BMD) and coronary artery calcification (CAC). We examined the observational association of BMD with CAC in 2 large population-based studies and evaluated the evidence for a potential causal relation between BMD and CAC using polygenic risk scores (PRS), 1- and 2-sample Mendelian randomization (MR) approaches. Our study populations comprised 1414 individuals (mean age 69.9yr, 52.0% women) from the Rotterdam Study and 2233 individuals (mean age 56.5yr, 50.9% women) from the Framingham Heart Study with complete information on CAC and BMD measurements at the total body (TB-), lumbar spine (LS-), and femoral neck (FN-). We used linear regression models to evaluate the observational association between BMD and CAC. Subsequently, we compared the mean CAC across PRSBMD quintile groups at different skeletal sites. In addition, we used the 2-stage least squares regression and the inverse variance weighted (IVW) model as primary methods for 1- and 2-sample MR to test evidence for a potentially causal association. We did not observe robust associations between measured BMD levels and CAC. These results were consistent with a uniform random distribution of mean CAC across PRSBMD quintile groups (P-value > .05). Moreover, neither 1- nor 2-sample MR supported the possible causal association between BMD and CAC. Our results do not support the contention that lower BMD is (causally) associated with an increased CAC risk. These findings suggest that previously reported epidemiological associations of BMD with CAC are likely explained by unmeasured confounders or shared etiology, rather than by causal pathways underlying both osteoporosis and vascular calcification processes.

Circulating isomiRs May Be Superior Biomarkers Compared to Their Corresponding miRNAs: A Pilot Biomarker Study of Using isomiR-Ome to Detect Coronary Calcium-Based Cardiovascular Risk in Patients with NAFLD.

Circulating miRNAs are increasingly being considered as biomarkers in various medical contexts, but the value of analyzing isomiRs (isoforms of canonical miRNA sequences) has not frequently been assessed. Here we hypothesize that an in-depth analysis of the full circulating miRNA landscape could identify specific isomiRs that are stronger biomarkers, compared to their corresponding miRNA, for identifying increased CV risk in patients with non-alcoholic fatty liver disease (NAFLD)-a clinical unmet need. Plasma miRNAs were sequenced with next-generation sequencing (NGS). Liver fat content was measured with magnetic-resonance spectrometry (MRS); CV risk was determined, beyond using traditional biomarkers, by a CT-based measurement of coronary artery calcium (CAC) score and the calculation of a CAC score-based CV-risk percentile (CAC-CV%). This pilot study included n = 13 patients, age > 45 years, with an MRS-measured liver fat content of ≥5% (wt/wt), and free of overt CVD. NGS identified 1103 miRNAs and 404,022 different isomiRs, of which 280 (25%) and 1418 (0.35%), respectively, passed an abundance threshold. Eighteen (sixteen/two) circulating miRNAs correlated positively/negatively, respectively, with CAC-CV%, nine of which also significantly discriminated between high/low CV risk through ROC-AUC analysis. IsomiR-ome analyses uncovered 67 isomiRs highly correlated (R ≥ 0.55) with CAC-CV%. Specific isomiRs of miRNAs 101-3p, 144-3p, 421, and 484 exhibited stronger associations with CAC-CV% compared to their corresponding miRNA. Additionally, while miRNAs 140-3p, 223-3p, 30e-5p, and 342-3p did not correlate with CAC-CV%, specific isomiRs with altered seed sequences exhibited a strong correlation with coronary atherosclerosis burden. Their predicted isomiRs-specific targets were uniquely enriched (compared to their canonical miRNA sequence) in CV Disease (CVD)-related pathways. Two of the isomiRs exhibited discriminative ROC-AUC, and another two showed a correlation with reverse cholesterol transport from cholesterol-loaded macrophages to ApoB-depleted plasma. In summary, we propose a pipeline for exploring circulating isomiR-ome as an approach to uncover novel and strong CVD biomarkers.

Artificial Intelligence in Coronary Artery Calcium Scoring Detection and Quantification.

Coronary artery calcium (CAC) is a marker of coronary atherosclerosis, and the presence and severity of CAC have been shown to be powerful predictors of future cardiovascular events. Due to its value in risk discrimination and reclassification beyond traditional risk factors, CAC has been supported by recent guidelines, particularly for the purposes of informing shared decision-making regarding the use of preventive therapies. In addition to dedicated ECG-gated CAC scans, the presence and severity of CAC can also be accurately estimated on non-contrast chest computed tomography scans performed for other clinical indications. However, the presence of such "incidental" CAC is rarely reported. Advances in artificial intelligence have now enabled automatic CAC scoring for both cardiac and non-cardiac CT scans. Various AI approaches, from rule-based models to machine learning algorithms and deep learning, have been applied to automate CAC scoring. Convolutional neural networks, a deep learning technique, have had the most successful approach, with high agreement with manual scoring demonstrated in multiple studies. Such automated CAC measurements may enable wider and more accurate detection of CAC from non-gated CT studies, thus improving the efficiency of healthcare systems to identify and treat previously undiagnosed coronary artery disease.

Impact of coronary artery calcium on the prognosis of heterozygous familial hypercholesterolemia

Abstract Aims This study was designed to examine the association between coronary artery calcium (CAC) and major adverse cardiac events (MACEs) and to estimate CAC progression in patients with familial hypercholesterolemia (FH) in primary prevention settings. Methods and results Data of patients with FH admitted to our university hospital between 2000 and 2020, who underwent CAC measurement and were followed up (N = 622, male = 306), were retrospectively reviewed. Risk factors for MACEs were determined using the Cox proportional hazard model. The median follow-up duration was 13.2 years (interquartile range: 9.8–18.4 years). We observed 132 MACEs during the follow-up period. The event rate per 1,000 person-years for CAC scores of 0 (N = 283 [45.5%]), 1–100 (N = 260 [41.8%]), and &amp;gt;100 (N = 79 [12.7%]) was 1.2, 17.0, and 78.8, respectively. Log (CAC score+1) was a significant predictor of the occurrence of MACEs (hazard ratio: 3.24; 95% confidence interval: 1.68–4.80; p = 5.6×10−5) in the multivariate Cox regression analysis, independent of other factors. The risk discrimination of MACEs was enhanced by adding CAC information to other conventional risk factors (C-statistics: 0.833–0.934; p = 1.4×10−15). The regression equations between age and the CAC score in male and female were Y = 0.074X–1.52 and Y = 0. 087X–3.21, respectively. Conclusion CAC score helps in further risk stratification in patients with FH. Furthermore, the average age of CAC onset was 21 years in male and 37 years in females.

Abstract 13721: Coronary Artery Calcium for Risk Stratification Among Persons With Very-High High-Density Lipoprotein Cholesterol

Introduction: Persons with very-high high-density lipoprotein-cholesterol (HDL-C) may experience an increased mortality risk. However, the predictors of mortality among those with very-high HDL-C remain unknown. Hypothesis: Compared to traditional risk factors, coronary artery calcium (CAC) will more strongly stratify risk among individuals with very-high HDL-C. Aims: Among individuals with very-high HDL-C, to 1) calculate crude all-cause mortality rates across the burden of traditional risk factors and CAC, and 2) identify independent risk factors associated with all-cause mortality. Methods: There were 335 primary prevention patients from the CAC Consortium who had very-high HDL-C ( &gt; 80 mg/dL in men, &gt; 100 mg/dL in women) and available information on traditional CVD risk factors. Crude all-cause mortality rates were calculated per 1,000 person-years. Multivariable Cox proportional hazards regression assessed the association of traditional risk factors and CAC with mortality. Results: The mean age was 58.6 years old, 51.0% were women, 51.3% had prevalent CAC, and the median HDL-C was 100 mg/dL. There were 20 deaths (6.0%) over a median follow-up of 10.5 years, 7 (2.1%) of which were attributable to CVD. There was a stepwise higher crude mortality rate per 1,000 person-years across increasing CAC burden ( Central Illustration ). Independent of traditional risk factors, each 100 Agatston Unit increase in CAC score was associated with a 7% higher hazard of all-cause mortality (HR: 1.07, 95% CI: 1.01-1.12) and individuals with CAC &gt; 1000 experienced a 5.75-fold higher hazard of mortality when compared to CAC=0 (HR: 5.75, 95% CI: 1.26-26.24). Beyond age, no traditional risk factor was associated with mortality in multivariable analyses. Conclusion: Measurement of CAC on non-contrast cardiac computed tomography may facilitate risk assessment among individuals with very-high HDL-C.

449-P: Truncations of Apolipoproteins C-I and C-II Are Associated with Coronary Artery Calcium Progression in Multiethnic Study of Atherosclerosis (MESA)

Higher 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, including lower triglycerides (TG) and higher HDL levels. Here we examined the relationships of C-I’/C-II and C-II’/C-II, and total apoC-I and apoC-II concentrations with coronary artery calcium (CAC) progression. Apo C-I and C-II proteoforms were measured by mass spectrometry immunoassay in 5,791 baseline MESA plasma samples. Total apo C-I and C-II concentrations were assayed in 3,851 samples. CAC was measured 1 to 4 times (mean 2.5) over 10 years. Repeated measures regression models were adjusted for age, gender, race/ethnicity, and follow-up time (Model 1), then for BMI, diabetes, systolic BP, use of tobacco, statins and antihypertensive medications (Model 2), and then for plasma HDL and TG (Model 3). Among 5,069 participants with at least one follow-up CAC CT scan, 2,513 had CAC progression defined as events of CAC changing from 0 to &amp;gt; 0, or ≥ 10 units/yr from CAC &amp;gt; 0 but ≤ 100, or ≥ 10%/yr from CAC &amp;gt; 100. Progression was inversely associated with C-I’/C-I (Risk Ratio per 1 SD: 0.93 [95% CI 0.87, 0.97], Model 3). In those with baseline CAC = 0 (n = 2,581), risk of CAC &amp;gt; 0 (897 events) was inversely associated with C-I’/C-I in Model 1 only (0.85 [0.79, 0.93]). In those with baseline CAC &amp;gt; 0, C-II’/C-II was positively associated with follow-up change in density score (β-estimate per 1 SD 0.02 [95% CI: 0.001, 0.03] units) in Model 3, indicating a potentially more stable plaque. Baseline-adjusted follow-up density score was also positively related to total apoC-I in Model 2 (0.02 [0.004, 0.04]). None of the CAC measures were related to total apoC-II. In conclusion, increased truncation of apo C-I and C-II is associated with reduced CAC progression and/or improved stability of coronary atherosclerotic plaque that is not explained by total concentrations of both apolipoproteins. Disclosure J.Koska: None. J.Furtado: Employee; Biogen. Y.Hu: None. D.Billheimer: Advisory Panel; AstraZeneca. M.Allison: None. M.Budoff: Research Support; Novo Nordisk, Novartis, Boehringer Ingelheim Inc., Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance. D.Nedelkov: None. R.Mcclelland: None. P.Reaven: Research Support; Dexcom, Inc. Funding National Heart, Lung, and Blood Institute (R01HL138969, 75N92020D00001, HHSN268201500003I, N01HC95159, 75N92020D00005, N01HC95160, 75N92020D00002, N01HC95161, 75N92020D00003, N01HC95162, 75N92020D00006, N01HC95163, 75N92020D00004, N01HC95164, 75N92020D000

Female specific cardiovascular risk factors

The proportion of total deaths attributable to CVD in Europe is greater for women (51%) than for men (42%). Classic manifestations of cardiovascular diseases (CVD) develop on average 7-10 years later in women than in men. The risk in women is systematically underestimated < 65 years of age, as we still consider them along the male standard. High risk women at middle-age often have (several) female-specific risk factors that are overlooked in the standard SCORE charts. These are for instance premenopausal migraine, multiple pregnancy losses, hypertensive pregnancy disorders, endometriosis, PCOS, early menopause etc. Measurement of Coronary Artery Calcium (CAC) scores with computed tomography (CT) scans is nowadays a well validated, safe and non-expensive tool to identify individuals at increased cardiovascular disease (CVD) risk at middle-age (> 40 years old). In the European and North American prevention lipid guidelines, the use of CAC is endorsed for risk clarification in patients at intermediate risk of CVD who may be good candidates for preventive therapies. The CAC score enables to identify high risk women that are overlooked in the commonly used SCORE charts. In this lecture an overview will be provided on the current knowledge of female-specific risk factors and how to use them in clinical practice.

Coronary artery calcium among patients with heterozygous familial hypercholesterolaemia.

We aimed to determine if coronary artery calcium (CAC) is associated with cardiovascular disease (CVD) events, defined as CVD-related death, unstable angina, myocardial infarction, or staged revascularization among patients with heterozygous familial hypercholesterolaemia (HeFH) under primary prevention settings. Data of patients with FH admitted to Kanazawa University Hospital between 2000 and 2020, who underwent CAC measurement and were followed up (n = 622, male = 306, mean age = 54 years), were retrospectively reviewed. Risk factors for CVD events were determined using the Cox proportional hazard model. The median follow-up duration was 13.2 years (interquartile range: 9.8-18.4 years). We observed 132 CVD events during the follow-up period. The event rate per 1000 person-years for CAC scores of 0 [n = 283 (45.5%)], 1-100 [n = 260 (41.8%)], and >100 [n = 79 (12.7%)] was 1.2, 17.0, and 78.8, respectively. Log (CAC score + 1) was a significant predictor of the occurrence of CVD events (hazard ratio: 3.24; 95% confidence interval: 1.68-4.80; P < 0.0001) in the multivariate Cox regression analysis, independent of other factors. The risk discrimination of CVD events was enhanced by adding CAC information to other conventional risk factors (C-statistics: 0.833-0.934; P < 0.0001). The CAC score helps in further risk stratification in patients with HeFH.

Coronary artery calcium progression and all-cause mortality.

Coronary artery calcium (CAC) has been demonstrated as a noninvasive, low-cost means of assessing atherosclerotic burden and risk of major cardiovascular events. While it has been previously shown that CAC progression predicts all-cause mortality, we sought to quantify this association by examining a large cohort over a follow-up period of 1-22 years. We studied 3260 persons aged 30-89 years referred by their primary physician for CAC measurement, with a follow-up scan at least 12 months from the initial scan. Receiver operator characteristic (ROC) curves assessed a level of annualized CAC progression that predicted all-cause mortality. Multivariate analyses using Cox proportional hazards models were used to compute hazard ratios and 95% confidence intervals (CIs) for the association between annualized CAC progression and death after adjusting for relevant cardiovascular risk factors. The average time between scans was 4.7 ± 3.2 years with an additional average of 9.1 ± 4.0 years of follow-up time. The average age of the cohort was 58.1 ± 10.5 years, 70% being male, and 164 deaths occurred. Annualized CAC progression of 20 units optimized sensitivity (58%) and specificity (82%) in ROC curve analysis. Annualized CAC progression of 20 units was significantly associated with mortality while adjusting for age, sex, race, diabetes, hypertension, hyperlipidemia, smoking, baseline CAC level, family history, and time between scans, hazard ratio 1.84 (95% CI, 1.28-2.64) P = 0.001. Annualized CAC progression of greater than 20 units per year significantly predicts all-cause mortality. This may add clinical value in encouraging close surveillance and aggressive treatment of individuals within this range.

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.

Coronary Artery Calcium Dispersion and Cause-Specific Mortality

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

High- vs. Low-Intensity Statin Therapy and Changes in Coronary Artery Calcification Density after One Year.

Statin therapy promotes the progression of coronary artery calcification (CAC). Comparing patients on high (HIST) vs. low-to-intermediate intensity statin therapy (LIST), randomized controlled trials with a one-year follow-up failed to document a relevant difference in the Agatston score and CAC volume. We evaluated whether statin intensity modifies CAC density at one year. We performed a pooled analysis of two randomized-controlled trials (BELLES, EBEAT), comparing the effects of HIST (Atorvastatin 80 mg) vs. LIST (Pravastatin 40 mg, Atorvastatin 10 mg) on CAC measures after one year. The differences in CAC density and its change were compared using the two-sided t-test. Data from 852 patients (66.7% female) with available baseline and follow-up CT were evaluated from both trials. HIST vs. LIST more effectively reduced LDL-cholesterol (annualized change: -45.8 ± 38.5 vs. -72.9 ± 46.0 mg/dL, p &lt; 0.001). Mean CAC density increased from 228.8 ± 35.4 HU to 232.6 ± 37.0 HU (p &lt; 0.0001) at one-year follow-up. Comparing patients on HIST vs. LIST, CAC density at follow-up (HIST: 231.9 ± 36.1 HU vs. LIST: 233.3 ± 37.7 HU, p = 0.59) and its change from baseline (HIST: 4.0 ± 19.1 HU vs. LIST: 3.6 ± 19.6 HU, p = 0.73) did not differ. Subgroup analyses, stratifying by LDL reduction (&lt;median: 2.0 ± 24.3 HU, ≥median: 3.6 ± 21.9 HU, p = 0.34), Agatston score at baseline (&lt;100: 2.6 ± 22.5 HU vs. 3.2 ± 25.6 HU, p = 0.82; ≥100: 4.8 ± 17.0 HU vs. 3.8 ± 16.6 HU, p = 0.44, for HIST vs. LIST; respectively), and equal number of lesions in both CT scans (3.7 ± 20.3 HU vs. 7.0 ± 22.2 HU, p = 0.24) showed similar results. HIST vs. LIST leads to a higher reduction in cholesterol levels, which does not translate into relevant differences in the change of CAC density at one-year follow-up.

Abstract 9971: Distribution of Coronary Artery Calcium and Risk for Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis

Introduction: We tested the hypothesis that specific arteries with coronary artery calcium (CAC) would be associated with higher risk for incident cardiovascular disease (CVD) outcomes, even after accounting for traditional risk factors, and that adding this metric to current risk scores would improve event prediction. Methods: We analyzed data from 3,255 MESA participants with baseline CAC and event follow-up. Cox proportional hazards models assessed the independent associations between CAC presence in each of the main coronary arteries and incident myocardial infarction (MI), hard coronary artery disease (CHD), and hard CVD, adjusting for the ASCVD risk score and CAC volume and density. Area under the receiver operating characteristic curve (AUC) analyses assessed for risk discrimination by adding CAC distribution to existing risk models. Results: At baseline [mean age 66 years (SD 9.6); 1,893 female (58%)], 2,909 (89%) participants had CAC in the left anterior descending (LAD), 1,871 (58%) in the left circumflex (LCx), 1,691 (52%) in the right coronary artery (RCA), and 693 (21%) in the left main (LM). Over a median of 15.5 years, 275 developed MI, 408 CHD, and 598 CVD. After adjustment for the ASCVD risk score and CAC volume and density, only the RCA remained significant for MI and CHD, and was borderline for CVD (Table). AUC increased after adding RCA CAC presence to the ASCVD risk score for MI (0.5992 to 0.6660; 95% CI 0.031-0.102) and CHD (0.6483 to 0.6818; 95% CI, 0.003-0.064), but not for CVD, and there was no significant increase for any endpoints when added to models accounting for CAC volume and density. Conclusion: Prevalent CAC was most common in the LAD, followed by the LCx and RCA. Accounting for risk factors and CAC measures, the RCA was the only artery independently associated with additional MI and CHD risk. Moreover, MI and CHD risk prediction were improved with the addition of CAC distribution to the ASCVD score but not when also accounting for CAC volume and density.

Abstract 10296: Relation of Lipoprotein(a) to Progression of Coronary Artery Calcium: Results From a Pooled Cohort of Mesa, Cardia, and Framingham Offspring Studies

Background: Lipoprotein(a) [Lp(a)] levels and coronary artery calcium (CAC) are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events. Progression of CAC is also associated with greater ASCVD risk. Less well-established is the relation of Lp(a) with progression of atherosclerosis as assessed by progression of CAC. Methods: We included a pooled cohort of 9454 persons without ASCVD at baseline (mean age 55.6 years, 53.5% female, and 31% black) and with multiple measures of CAC (up to 4 over a mean of 7.3 + 3.3 years from baseline CAC measures) from the Multiethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, and Framingham Offspring Studies. Lp(a) was assessed continuously and by category (&lt;15 mg/dL [reference], 15-29 mg/dL, 30-49 mg/dL, 50-69 mg/dL, 70-89 mg/dL, and &gt; 90 mg/dL) in relation to progression of CAC (annualized change in Agatston score) incorporating multiple CAC measures utilizing mixed model regression with time (in years), adjusted for age, sex, race, baseline CAC, and other covariates. Subgroup analyses were done separately in those with baseline CAC. Results: A 50 mg/dL increment of Lp(a) was associated with an adjusted annualized change in CAC score of 3.97 units. Compared to those with Lp(a) levels of &lt;15 mg/dL, those with levels of 50-69 mg/dL, 70-89 mg/dL, and &gt; 90 mg/dL had a statistically significant annualized progression of CAC that was 3.09, 8.70, and 9.46 units greater in adjusted analyses. Progression was greater in those with baseline CAC&gt;0 (Table). Conclusions: Higher levels of Lp(a) are associated with greater progression of atherosclerosis as measured by CAC scores.

Alpha 2-Heremans-Schmid glycoprotein gene polymorphism (rs4918) is associated with coronary artery calcification in incident peritoneal dialysis patients.

Coronary artery calcification (CAC) is a common and severe complication in peritoneal dialysis (PD) patients, and it progresses in a majority of patients. Fetuin-A, encoded by the alpha 2-Heremans-Schmid glycoprotein (AHSG) gene, is a serum calcification inhibitor. The study aimed to examine the role of AHSG gene polymorphism rs4918 in CAC and CAC progression of PD patients. Incident PD patients at Huashan Hospital Fudan University in China from August 2007 to July 2018 were recruited in this prospective study and followed up for 2 years. Patients underwent CAC measurements at recruitment and 2 years later. AHSG gene polymorphism rs4918 and serum fetuin-A were determined at baseline. The demographic characteristics, clinical data, and laboratory data were collected during the follow-up period. Binary logistic regression was performed to explore the association between rs4918 with CAC and CAC progression. A total of 202 PD patients (112 men, 55.4%) were recruited, with a mean age of 54 ± 16 years. The multivariate logistic regression identified genotype GG as an independent risk factor that correlates to CAC (odds ratio [OR]=2.153; 95% CI: 1.182-3.925; p=.012) and CAC progression (OR=2.482; 95% CI: 1.422-4.330; p=.001). The serum fetuin-A level was influenced by the rs4918 variants of AHSG, with a dose-dependent effect depending on the number of the G allele. AHSG gene polymorphism rs4918 affects serum fetuin-A levels and is significantly associated with both CAC and CAC progression in a cohort of patients receiving PD.

Heterogeneity in the Association Between the Presence of Coronary Artery Calcium and Cardiovascular Events: A Machine-Learning Approach in the MESA Study.

Coronary artery calcium (CAC) has been widely recognized as an important predictor of cardiovascular disease (CVD). Given the finite resources, it is important to identify individuals who would receive the most benefit from detecting positive CAC by screening. However, the evidence is limited as to whether the burden of positive CAC on CVD differs by multidimensional individual characteristics. We sought to investigate the heterogeneity in the association between positive CAC and incident CVD. This cohort study included adults from MESA (Multi-Ethnic Study of Atherosclerosis) ages ≥45 years and free of cardiovascular disease. After propensity score matching in a 1:1 ratio, we applied a machine learning causal forest model to (1) evaluate the heterogeneity in the association between positive CAC and incident CVD, and (2) predict the increase in CVD risk at 10-years when CAC>0 (versus CAC=0) at the individual level. We then compared the estimated increase in CVD risk when CAC>0 to the absolute 10-year atherosclerotic CVD (ASCVD) risk calculated by the 2013 American College of Cardiology/American Heart Association pooled cohort equations. Across 3328 adults in our propensity score-matched analysis, our causal forest model showed the heterogeneity in the association between CAC>0 and incident CVD. We found a dose-response relationship of the estimated increase in CVD risk when CAC>0 with higher 10-year ASCVD risk. Almost all individuals (2293 of 2428 [94.4%]) with borderline risk of ASCVD or higher showed ≥2.5% increase in CVD risk when CAC>0. Even among 900 adults with low ASCVD risk, 689 (69.2%) showed ≥2.5% increase in CVD risk when CAC>0; these individuals were more likely to be male, Hispanic, and have unfavorable CVD risk factors than others. The expected increases in CVD risk when CAC>0 were heterogeneous across individuals. Moreover, nearly 70% of people with low ASCVD risk showed a large increase in CVD risk when CAC>0, highlighting the need for CAC screening among such low-risk individuals. Future studies are needed to assess whether targeting individuals for CAC measurements based on not only the absolute ASCVD risk but also the expected increase in CVD risk when CAC>0 improves cardiovascular outcomes.

Cholesterol mass efflux capacity and coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis

We assessed the cross-sectional and longitudinal relationships of high-density lipoprotein (HDL)-mediated cholesterol mass efflux capacity (CMEC) with coronary artery calcium (CAC) score and CAC density. CMEC was measured in 1626 Multi-Ethnic Study of Atherosclerosis (MESA) participants in samples obtained between 2000 and 2002 as part of two nested case-control studies, one with cases of incident cardiovascular disease and the other with cases of carotid plaque progression by ultrasound. Cardiac CT examinations for the presence of CAC were performed at baseline and at two additional examinations. CAC scores (Agatston and volume) and density scores (for those with positive CAC) were calculated. Multivariable linear regression modeling per SD increment of CMEC was used to estimate the associations of CMEC with each of these CAC measures. We found no association between higher CMEC and either lower CAC scores or a higher CAC density. We also found no association between higher CMEC and progression of any of these CAC measures. These findings suggest that HDL-mediated cholesterol efflux may be associated with cardiovascular risk via mechanisms unrelated to burden of calcified plaque.