Coronary Artery Calcification In Women Research Articles

Impaired metabolism predicts coronary artery calcification in women with systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases (CVD) which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which can contribute to the elevated prevalence of CVD. A comprehensive analysis of the circulating metabolome and lipidome was conducted in a large cohort of 211 women with SLE who underwent a multi-detector computed tomography scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD). Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factors for developing CAC in women with SLE. The presence of coronary calcium was associated with major alterations of circulating lipidome dominated by an elevated abundance of ceramides with very long chain fatty acids. Alterations in multiple metabolic pathways, including purine, arginine and proline metabolism, and microbiota-derived metabolites, were also associated with CAC in women with SLE. Logistic regression with bootstrapping of lipidomic and metabolomic variables were used to develop prognostic scores. Strikingly, combining metabolic and lipidomic variables with clinical and biological parameters markedly improved the prediction (area under the curve: 0.887, p<0.001) of the presence of coronary calcium in women with SLE. The present study uncovers the contribution of disturbed metabolism to the presence of coronary artery calcium and the associated risk of CHD in SLE. Identification of novel lipid and metabolite biomarkers may help stratifying patients for reducing CVD morbidity and mortality in SLE. INSERM and Sorbonne Université.

Higher exercise capacity, but not omega-3 fatty acid consumption, predicts lower coronary artery calcium scores in women and men with coronary artery disease

Background and aimsHigher coronary artery calcium (CAC) scores are associated with increased cardiovascular (CVD) events and mortality. Exercise capacity is predictive of CVD events. Our aim was to examine the relationship between exercise capacity and CAC in women and men. MethodsCAC was measured in 203 men and 38 women with clinical coronary artery disease using multidetector coronary tomography. They were randomized to 3.36 g eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily or none for 30 months. Maximal exercise treadmill testing was performed at baseline with calculation of metabolic equivalents of task (METs) achieved as a measure of exercise capacity. ResultsDespite similar ages at baseline (64.0 ± 6.7 vs 62.7 ± 7.8 years, respectively, p = 0.225), women had lower CAC scores compared to men: 106.7 Agatston units [AU] vs 535.3, respectively, p < 0.001, and at every age (p < 0.001). Female CAC scores did not equal those of men until women were 20 years older. Higher levels of METs were associated with lower CAC scores in both women and men. After multivariate adjustment, METs was the most important predictor of CAC score in women at baseline and 30 months (p = 0.001 and 0.029, respectively) whereas only age predicted in men (p = 0.019 and 0.004, respectively). Annual CAC progression was significantly greater in men compared to women (94.8 AU/year vs 38.0, respectively, p = 0.014). No difference was observed in CAC progression in the EPA + DHA group compared to control in either men or women. ConclusionsThe association of higher METs with lower CAC scores in both women and men supports recommending exercise to maximize cardiorespiratory fitness as this may minimize CAC scores and thus, potentially decrease risk for CVD events. This may be especially important for women since METs independently predicted baseline and 30 month CAC in women.

Coronary Artery Calcification in women with a premenopausal RRSO compared to women with a postmenopausal RRSO

Introduction: BRCA1/2 pathogenic variant carriers are recommended to undergo premenopausal risk-reducing salpingo-oophorectomy (RRSO) to prevent ovarian cancer, leading to immediate surgical menopause. Although studies show that women with natural premature ovarian are at increased risk of developing cardiovascular disease (CVD), evidence about long-term CVD risk after early surgical menopause is scarce.

Sex differences in the association between minor nonspecific ST-segment and T-wave abnormalities and coronary artery calcification

Background and aimsAlthough minor nonspecific ST-segment and T-wave abnormalities (NSSTTA) have been associated with adverse cardiovascular outcomes, their relationship with subclinical atherosclerosis remains controversial. Therefore, the associations between electrocardiographic (ECG) abnormalities, including NSSTTA, and coronary artery calcification (CAC) were investigated in this study. MethodsThis cross-sectional study included 136,461 Korean participants with no known cardiovascular disease or cancer, who underwent a health checkup including ECG and computed tomography to measure the coronary artery calcium score (CACS) by Agatston method between 2010 and 2018. ECG abnormalities were defined in accordance with the Minnesota Code using an automated ECG analysis program. A multinomial logistic regression model was used to calculate prevalence ratios (PRs) with 95% confidence intervals (CI) for each CACS category. ResultsIn men, both NSSTTA and major ECG abnormalities were associated with all levels of CACS. The multivariable-adjusted PRs (95% CI) for CACS >400 comparing NSSTTA and major ECG abnormalities to the reference (neither NSSTTA nor major ECG abnormalities) were 1.88 (1.29–2.74) and 1.50 (1.18–1.91), respectively. Women with major ECG abnormalities were more likely to have a CACS of 101–400, the PRs (95% CI) comparing major ECG abnormalities to the reference group was 1.75 (1.18–2.57). NSSTTA were not associated with any CACS level in women. ConclusionsNSSTTA and major ECG abnormalities are associated with CAC in men, though NSSTTA were not associated with CAC in women, suggesting that NSSTTA should be considered sex-specific risk factors for coronary artery disease in men, but not in women.

Abstract 39: Association of Cardiovascular Health With Time Lived Free of Coronary Artery Calcium

Introduction: Zero coronary artery calcium (CAC) is associated with lower risk of cardiovascular disease. More time lived without CAC may delay coronary artery disease morbidity, but prediction of when CAC will first develop is not well understood. To inform cardiovascular prevention, we evaluated how cardiovascular health (CVH) relates to time lived without CAC. Methods: In Multi-Ethnic Study of Atherosclerosis (MESA) participants with zero CAC at baseline followed up to 10 years, we used Kaplan-Meier curves to estimate restricted mean survival time since study entry lived with zero CAC, by baseline CVH per Life’s Simple 7 metrics categorized as high (score 12-14), moderate (8-11), and low (0-7), and stratified by sex and age (45-64, 65-84 years). Results: Among 3416 participants without CAC at baseline (63% female, mean age 58 [SD 9] years, mean CVH score 8.8 [2.1]), mean years lived with zero CAC was 4.9 (SD 3.5) years. Women with high CVH lived on average 6.6 (95% CI 6.4-6.8) years with zero CAC, with moderate CVH 6.2 (6.1-6.3) years with zero CAC, and with low CVH 5.6 (5.3-5.8) years with zero CAC. Men with high CVH lived on average 6.4 (5.9-6.9) years with zero CAC, with moderate CVH 6.1 (5.9-6.3) years with zero CAC, and with low CVH 5.5 (5.1-5.9) years with zero CAC (Figure A). Among participants aged 45-64 years, those with high CVH lived on average 7.4 (7.1-7.6) years with zero CAC, with moderate CVH 6.8 (6.6-6.9) years with zero CAC, and with low CVH 5.9 (5.7-6.2) years with zero CAC. Among participants aged 65-84 years, those with high CVH lived on average 5.1 (4.5-5.7) years with zero CAC, with moderate CVH 5.2 (5.0-5.4) years with zero CAC, and with low CVH 4.9 (4.6-5.2) years with zero CAC (Figure B). Conclusions: High CVH was associated with longer time lived with zero CAC in women and men. Adults aged 45-64 years with high or intermediate CVH at baseline had longer time lived with zero CAC compared with those with low CVH. Older adults had no difference in time lived with zero CAC based on CVH. Maintaining CVH in midlife may delay onset of CAC.

Abstract P337: Determinants and Influence of Breast Arterial Calcifications on Risk of Cardiovascular Disease

Background: Breast arterial calcifications (BAC) are incidentally observed on screening mammography. BAC has been shown to be associated with the presence of coronary artery calcification (CAC) and increased risk of coronary artery disease (CAD). Given that population-based mammography is currently recommended to women, the evaluation of BAC may be important in identifying high-risk women without additional cost or radiation exposure. Aims: We sought to identify reproductive and cardiovascular risk factors associated with the presence of detectable BAC and CAC in women participated to mammography screening. Also, we aimed to determine the association between BAC and presence of CAC. Further, we investigated presence of BAC, CAC and estimated 10-year risk of atherosclerotic cardiovascular disease (ASCVD). Methods: In this cross-sectional study, reproductive history and CVD risk factors were obtained in 215 women ≥ 18 years of age that underwent mammography and cardiac computed tomographic angiography (CCTA) within 2 years of each other between January 2007 and September 2017 at Weill Cornell Medicine/ New York Presbyterian hospital (WCM/NYP). BAC was recorded in two ways: a binary scale (presence/absence) and a semi-quantitative scale (mild, moderate, severe). CAC was calculated using the Agatston method and was recorded as a binary variable (presence/absence). Information regarding reproductive history and CVD risk factors, medical history, and relevant demographics were obtained by chart review. Odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for age at study entry as a potential confounder, were estimated. The 10-year risk of atherosclerotic cardiovascular disease (ASCVD) was calculated using the Pooled Cohort Risk Equations. Results: The odds of presence of BAC increased with increasing age . Women age ≥60 had a near 6-fold higher odds of BAC (OR = 5.77; 95% CI = 2.45 to 16.00) compared with women &lt;60 years old. Other factors associated with presence of BAC after controlling for age were diastolic blood pressure ≥80 ( P = 0.0008), systolic blood pressure ≥140 ( P = 0.0009), number of children (P = 0.01). Younger age at first birth (≤28 years) was associated with 3-fold higher odds of BAC compared with women with age at first birth &gt;28 years. Except for age at study entry, the only factor associated with presence of CAC was hyperlipidemia ( P = 0.002). We found no association between presence of BAC with CAC. We observed women with presence of both BAC and CAC had the highest estimated 10-year risk of ASCVD: 18.54%, followed by presence of BAC but absence of CAC 11.65%, absence of BAC and presence of CAC 6.01%, and women with no BAC and no CAC presence had a mean 10-year risk of ASCVD of 5.25%. Conclusions: These findings support the value of BAC in identifying women at potentially increased risk of future cardiovascular disease without additional cost and radiation exposure.

Association of Trabecular Bone Score-Adjusted Fracture Risk Assessment Tool with Coronary Artery Calcification in Women.

The trabecular bone score (TBS) was found to be significantly associated with moderate coronary artery calcification (CAC). The aim of this study was to further explore the association between TBS-adjusted Fracture Risk Assessment Tool (FRAX) and CAC score in women. The electronic medical record database of a regional teaching hospital in southern Taiwan yielded women who received both coronary computed tomography and bone mineral density (BMD) measurement during their general health examination. Health history, anthropomorphic measurements, laboratory results, BMD, and T-scores were obtained. TBS values were calculated from database spine dual-energy X-ray absorptiometry files. Linear regression analyses tested the association between CAC score and 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) determined by TBS-adjusted FRAX. Of the 116 women (mean age 55.8 years) studied, 24.1% had osteoporosis. Simple linear regression showed a significant association of CAC score with an increase in MOF and HF risk as measured by TBS-adjusted FRAX. In multiple linear regression adjusted for potential confounders, CAC score remained significantly associated with TBS-adjusted FRAX for right MOF (p = 0.002), left MOF (p = 0 006), right HF (p = 0.005), and left HF (p = 0.015). In conclusion, clinicians should be vigilant to the potential increased risk of coronary events among women with increased TBS-adjusted FRAX for MOF and HF.

Associations of endogenous sex hormone levels with the prevalence and progression of valvular and thoracic aortic calcification in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aimsSex hormones (SH) may contribute to sex differences in cardiovascular disease (CVD). High free testosterone (T) and low sex hormone binding globulin (SHBG) have been associated with progression of coronary artery calcification in women. We now examined the association of SH with extra-coronary calcification (ECC) prevalence and progression among MESA participants. MethodsWe studied 2,737 postmenopausal women and 3,130 men free of clinical CVD with baseline SH levels. ECC measurements [ascending and descending thoracic aortic calcification (ATAC, DTAC), mitral annular calcification (MAC), aortic valve calcification (AVC)] were obtained by computed tomography at baseline and after 2.4 ± 0.9 years. We used multivariable Poisson regression to evaluate associations with ECC prevalence and incidence (Agatston scores >0) and linear mixed effects models for ECC progression, per 1-SD increment in log(SH) in women and men separately. ResultsThe mean age was 65 ± 9 and 62 ± 10 years for women and men, respectively. In women, greater free T and lower SHBG were associated with MAC incidence in a demographic-adjusted model only. In men, lower free T was associated with MAC prevalence, DTAC incidence and progression, while greater SHBG was associated with MAC prevalence and DTAC progression after further adjusting for CVD risk factors. ConclusionsIn this diverse cohort free of CVD, we found some associations of SH with ECC measures. In particular, free T was inversely associated with prevalent MAC and DTAC progression in men independent of CVD risk factors. SH may influence vascular calcification, but further work is needed to understand clinical implications of these findings.

Sex Differences in Coronary Arterial Calcification in Symptomatic Patients

Despite the increasing use of Coronary Artery Calcium (CAC) scoring for cardiovascular risk stratification in asymptomatic patients, the gender differences in CAC among symptomatic patients have not been well evaluated. We analyzed patients presenting to the emergency department (ED) with chest pain suggesting possible coronary artery disease (CAD) who received coronary computed tomography angiography (CCTA). Ordinal logistic regression was used to determine the odds ratio for the association of traditional cardiovascular risk factors and CAC. Patients with a CAC score ≥ 100 were followed for cardiovascular events or changes in medical management. Our cohort included 542 individuals (263 male, 279 female). Ordinal logistic regression model showed that among traditional cardiovascular risk factors, male sex had the highest odds ratio (OR) of 3.04 (p < 0.001, 95% CI [2.01, 4.59]) for the presence of CAC. Also, males had more diffuse distribution of coronary atherosclerosis (p=0.01). Subgroup analysis revealed that obesity was a bigger risk factor in male patients (OR 2.16), while smoking showed the greatest effect (OR 4.27) on CAC in women. Of patients who had CAC > 100 with an average follow-up of 346 days, there was an increase in both aspirin and statin use, yet significant sex differences were observed especially in patients with non-obstructive lesions on CCTA. Among male patients with non-obstructive lesions, 68.2% were on aspirin and 86.4% were on statin therapy after the CCTA compared to 27.3% and 45.5% respectively in their female counterparts. In conclusion, sex not only is the most powerful predictor for higher CAC among traditional cardiovascular risk factors in symptomatic patients but also influences the contribution of various traditional risk factors to elevated CAC. Furthermore, the discovery of CAD led to the initiation of medical therapy in male patients more frequently than in female patients, even after adjusting for the degree of luminal stenosis detected on coronary CT angiography.

Gestational Diabetes History and Glucose Tolerance After Pregnancy Associated With Coronary Artery Calcium in Women During Midlife: The CARDIA Study.

Gestational diabetes (GD) leads to earlier onset and heightened risk of type 2 diabetes, a strong risk factor for cardiovascular disease (CVD). However, it is unclear whether attaining normoglycemia can ameliorate the excess CVD risk associated with GD history. This study sought to evaluate GD history and glucose tolerance after pregnancy associated with coronary artery calcification (CAC) in women, a manifestation of atherosclerotic CVD and a predictor of CVD clinical events. Data were obtained from the CARDIA study (Coronary Artery Risk Development in Young Adults), a US multicenter, community-based prospective cohort of young Black (50%) and White adults aged 18 to 30 years at baseline (1985-1986). The sample included 1133 women without diabetes at baseline, who had ≥1 singleton births (n=2066) during follow-up, glucose tolerance testing at baseline and up to 5 times during 25 years (1986-2011), GD status, and CAC measurements obtained from 1 or more follow up examinations at years 15, 20, and 25 (2001-2011). CAC was measured by noncontrast cardiac computed tomography; dichotomized as Any CAC (score>0) or No CAC (score=0). Complementary log-log models for interval-censored data estimated adjusted hazard ratios of CAC and 95% confidence intervals for GD history and subsequent glucose tolerance groups (normoglycemia, prediabetes, or incident diabetes) on average 14.7 years after the last birth adjusted for prepregnancy and follow-up covariates. Of 1133 women, 139 (12.3%) reported GD and were 47.6 years of age (4.8 SD) at follow-up. CAC was present in 25% (34/139) of women with GD and 15% (149/994) of women with no GD. In comparison with no GD/normoglycemia, adjusted hazard ratios (95% CIs) were 1.54 (1.06-2.24) for no GD/prediabetes and 2.17 (1.30-3.62) for no GD/incident diabetes, and 2.34 (1.34-4.09), 2.13 (1.09-4.17), and 2.02 (0.98-4.19) for GD/normoglycemia, GD/prediabetes, and GD/incident diabetes, respectively (overall P=0.003). Women without previous GD showed a graded increase in the risk of CAC associated with worsening glucose tolerance. Women with a history of GD had a 2-fold higher risk of CAC across all subsequent levels of glucose tolerance. Midlife atherosclerotic CVD risk among women with previous GD is not diminished by attaining normoglycemia.

Sex Differences in Coronary Artery Calcium and Mortality From Coronary Heart Disease, Cardiovascular Disease, and All Causes in Adults With Diabetes: The Coronary Calcium Consortium.

While diabetes has been previously noted to be a stronger risk factor for cardiovascular disease (CVD) in women compared with men, whether this is still the case is not clear. Coronary artery calcium (CAC) predicts coronary heart disease (CHD) and CVD in people with diabetes; however, its sex-specific impact is less defined. We compared the relation of CAC in women versus men with diabetes for total, CVD, and CHD mortality. We studied adults with diabetes from a large registry of patients with CAC scanning with mortality follow-up over 11.5 years. Cox regression examined the relation of CAC with mortality end points. Among 4,503 adults with diabetes (32.5% women) aged 21-93 years, 61.2% of women and 80.4% of men had CAC >0. Total, CVD, and CHD mortality rates were directly related to CAC; women had higher total and CVD death rates than men when CAC >100. Age- and risk factor-adjusted hazard ratios (HRs) per log unit CAC were higher among women versus men for total mortality (1.28 vs. 1.18) (interaction P = 0.01) and CVD mortality (1.47 vs. 1.27) (interaction P = 0.04) but were similar for CHD mortality (1.48 and 1.48). For CVD mortality, HRs with CAC scores of 101-400 and >400 were 3.67 and 6.27, respectively, for women and 1.63 and 3.48, respectively, for men (interaction P = 0.04). For total mortality, HRs were 2.56 and 4.05 for women, respectively, and 1.88 and 2.66 for men, respectively (interaction P = 0.01). CAC predicts CHD, CVD, and all-cause mortality in patients with diabetes; however, greater CAC predicts CVD and total mortality more strongly in women.

Abstract P126: Comparing Cardiovascular Risk Factor Progression Between South Asian Men and Women With Diabetes: A Longitudinal Analysis From the Masala Study

Introduction: South Asians have a high incidence of type 2 diabetes(DM) and cardiovascular disease (CVD). Women with DM may have greater CVD risk compared to men with DM and women without DM. No study has determined whether the incidence or progression of coronary artery calcium (CAC) score, a measure of atherosclerosis burden, differs between South Asian men and women with DM. Hypothesis: We hypothesize that CAC progression is greater in women with DM as compared to men with DM and women without DM. Methods: We used the data from the MASALA study, a community-based prospective cohort of South Asians from 2 clinical sites without CVD at baseline. We conducted a longitudinal analysis of diabetic participants who were reassessed after 5 years and compared with those without diabetes. We classified incident CAC as any CAC at exam 2 in a participant who had no CAC at baseline. To examine the progression of CVD risk factors over time, we compared change in CAC score, waist circumference, systolic and diastolic blood pressure, HbA1c and lipid levels amongst the diabetic and non-diabetic population by sex. We conducted multivariable linear regression models stratified by diabetes status to determine whether sex was independently associated with change in CAC score and other CVD risk factors. Results: Of 749 participants who were seen in follow-up, 176 (23%) had diabetes at baseline, 65% were men, and mean age was 58 years. Approximately 64% women with DM vs. 28% men with DM had CAC=0, and men had higher median CAC score (49 (IQR 0-247) vs. 0 (IQR 0-46, p&lt;0.001). After mean follow-up of 4.8±0.8 years, incident CAC did not differ between men and women with diabetes (p=0.85). Progression of CAC was greater in men with DM (94, IQR 13-290) compared to women with DM (0, IQR 0-30) (p &lt;0.001). Baseline statin and aspirin use was lower in women with DM (statins: 37% in women vs. 56% in men, p&lt;0.001; aspirin 16% in women vs. 43% in men, p&lt;0.001). In multivariable models, the fold-change in CAC in women (0.22, 95% CI 0.10 - 0.47) was lower than in men (4.54, 95% CI 2.08 - 9.89) and comparable to women without DM (0.30 95%CI 0.21 -0.43), after adjusting for age, baseline CAC, systolic and diastolic blood pressure, total and LDL cholesterol, duration of diabetes, smoking and any medication use (statin, diabetes, or hypertension med). Sex was not associated with change in any CVD risk factor among those with diabetes; but women without DM had greater change in total and LDL cholesterol and waist circumference than men without DM. Conclusion: In this South Asian population, change in CAC score was lower in women with DM than in men with DM, and was comparable to women without DM. These results suggest among South Asians with DM, overall CVD risk may be greater in men than in women.Continued follow-up of the MASALA cohort will determine whether there are sex differences in CVD outcomes.

Abstract 07: Association of Social Network Characteristics With Cardiovascular Health and Coronary Artery Calcium in South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study

Introduction: South Asian Americans (SAs) have disproportionately high burden of poor cardiovascular health (CVH) and CVD, which may be influenced by people within their social network (SN). We examined the association of SN characteristics and SN member (“alter”) health with CVH and coronary artery calcium (CAC) in SAs to identify targets for CVD prevention in this high-risk community. Hypothesis: Smaller SN size and worse alter health is associated with poor CVH and CAC in SAs. Methods: In 699 SAs in the MASALA Study, SN characteristics (size, density, proportion of kin or SA ethnicity), alter health status (self-report of an alter with high blood pressure [HTN], hyperlipidemia [HL], heart disease, diabetes, or stroke), CVH score (0-14, based on poor, intermediate, or ideal blood pressure, cholesterol, glucose, physical activity, diet, weight, and smoking), and CAC data were collected between 2016-2018. Multiple logistic regression evaluated the association of SN characteristics or alter health with prevalent CVH and CAC. Results: Participants were mean age 59±9 years and 43% women. Mean CVH score was 8.9±1.9, median CAC score 8 (range 0 - 4217). SNs were mean 6±3 people, density 79±26%, 72±28% kin, 88±23% SA ethnicity; 48% had an alter with HTN, 42% with HL, 18% with heart disease, 40% with diabetes, and 2% with stroke. A 1-person larger SN size was associated with a 19% higher odds of ideal vs. poor CVH in men (p=0.02), and an 11% lower odds of CAC in women (p=0.05, Table). In men, having at least 1 alter with HTN or HL was associated with a 58% or 54% lower odds of ideal vs. poor CVH (p=0.03, p=0.04), and having at least 1 alter with HL was associated with a 78% higher odds of CAC (p=0.05). No associations were seen between other SN characteristics, nor alters with other CVD risk factors, and CVH or CAC. Conclusions: In SAs, larger SN size was associated with better CVH. Having a SN member with HTN or HL may be associated with poorer CVH and CAC. Interventions to increase SN size or target SN member CVH may promote CVH in this high-risk population.

Abstract P435: Associations of Endogenous Sex Hormone Levels With the Prevalence and Progression of Valvular and Thoracic Aortic Calcification in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Sex hormone (SH) levels may contribute to sex differences in cardiovascular disease (CVD) risk among women and men. We previously found that high free testosterone (T) and low sex hormone binding globulin (SHBG) were associated with progression of coronary artery calcification in women. Extra-coronary calcification (ECC) predicts incident clinical CVD independent of traditional risk factors. We examined whether SH were also associated with ECC prevalence and progression among MESA participants free of clinical CVD at baseline. Methods: We studied 2883 postmenopausal women and 3164 men who had endogenous SH levels measured at baseline. ECC was measured by non-contrast cardiac CT at baseline and at a follow-up visit up to 5 years later. ECC included ascending and descending thoracic aortic calcification (ATAC, DTAC), mitral annular calcification (MAC) and aortic valve calcification (AVC). We used multivariable Poisson regression to evaluate associations with ECC prevalence and risk of developing ECC (Agatston scores &gt;0) and linear mixed effects models for ECC progression, per 1 SD increment in log (SH) level in women and men separately. Results: The mean (SD) age was 64 (9) years for women and 62 (10) years for men. In women, greater free T and lower SHBG were associated with MAC incidence in a demographic-adjusted model but were no longer statistically significant after adjustment for CVD risk factors ( Table ). In men, lower free T was associated with MAC prevalence, DTAC incidence and progression while greater SHBG was associated with MAC prevalence and DTAC progression in fully adjusted models. We did not find associations of SH with AVC or ATAC in either men or women. Conclusion: In this diverse cohort free of CVD, we found certain associations of SH with measures of ECC. In particular, free T was inversely associated with prevalent MAC and DTAC progression in men independent of CVD risk factors. SH may influence vascular calcification but further work is needed to understand the clinical implications of these findings.

Early Onset of Coronary Artery Calcification in Women With Previous Preeclampsia.

Preeclampsia, coronary artery calcification (CAC), and atherosclerotic plaque are risk factors for the development of cardiovascular disease. We determined at what age CAC becomes apparent on coronary computed tomography after preeclampsia and to what extent modifiable cardiovascular risk factors were associated. We measured cardiovascular risk factors, CAC by coronary computed tomography, and coronary plaque by coronary computed tomography angiography in 258 previously preeclamptic women aged 40-63. Results were compared to 644 age- and ethnicity-equivalent women from the Framingham Heart Study with previous normotensive pregnancies. Any CAC was more prevalent after preeclampsia than after a normotensive pregnancy (20% versus 13%). However, this difference was greatest and statistically significant only in women ages 45 to 50 (23% versus 10%). The degree of CAC advanced 4× faster between the ages of 40 to 45 and ages 45 to 50 in women with a history of preeclampsia (odds ratio, 4.3 [95% CI, 1.5-12.2] versus odds ratio, 1.2 [95% CI, 0.6-2.3]). Women with a preeclampsia history maintained greater advancement of CAC with age into their early 60s, although this difference declined after the perimenopausal years. Women with a previous normotensive pregnancy were 4.9 years (95% CI, 1.8-8.0) older when they had similar CAC scores as previously preeclamptic women. These observations were not explained by the greater prevalence of cardiovascular disease risk factors, and the higher Framingham Risk Scores also observed in women with a history of preeclampsia. Previously preeclamptic women have more modifiable cardiovascular risk factors and develop CAC ≈5 years earlier from the age of 45 years onwards compared to women with normotensive pregnancies. Therefore, women who experienced preeclampsia might benefit from regular cardiovascular screening and intervention before this age. Registration: URL: https://www.trialregister.nl/trial/5406; Unique identifier: NTR5531.

Pericardial Adipose Tissue and Coronary Calcium in Type 1 Diabetes—The CACTI Study

Type 1 diabetes (T1D) and menopause are associated with higher risk of coronary artery calcium (CAC). Accumulation of pericardial adipose tissue (PAT), a pro-inflammatory visceral fat higher in post-menopausal women and associated with increased CAC, may be a mechanism by which T1D is associated with higher CAC risk. We examined the effect of PAT on the relationship between T1D and CAC in women over time. PAT and CAC volume data were collected from CT heart scans over 4 study visits from 725 women enrolled in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study (mean baseline age ± SD, 37 ± 9 years). We used repeated measures modeling to examine changes in square root-transformed CAC volume over time by T1D, menopausal status, and quartile of PAT volume after adjusting for age, central obesity, and study visit. PAT levels did not differ by T1D status (33.5 vs. 33.7, p=0.8), but there was a significant interaction between PAT, menopause, and T1D (p=0.02) in relation to CAC volume (Figure 1). In T1D women, higher PAT was associated with higher CAC volume regardless of menopause status, but the effect was greater in post-menopausal women. There was no difference in CAC in nondiabetic (non-DM) women across PAT quartiles or by menopause status. CAC was higher in T1D than non-DM women regardless of menopause status and PAT quartile. PAT has a greater effect on CAC in women with T1D than non-DM women, despite similar PAT volumes. Disclosure A. Keshawarz: None. L. Pyle: None. A.C. Alman: None. C. Sassano: None. E. Westfeldt: None. R.M. Sippl: None. J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation.

Blood Pressure Patterns and Subsequent Coronary Artery Calcification in Women Who Delivered Preterm Births.

Women who delivered preterm infants have excess cardiovascular disease, but vascular pathways linking these conditions are not understood. We considered that higher blood pressure over 25 years among women with preterm delivery may be associated with coronary artery calcification (CAC). The CARDIA study (Coronary Artery Risk Development in Young Adults) enrolled 1049 black and white women with births between 1985 and 2010 (n=272 ever preterm [<37 weeks]; n=777 all term births [≥37 weeks]). Latent mixture modeling identified blood pressure trajectories across 20 years, and these were related to CAC at years 20 and 25. Three systolic blood pressure (SBP) patterns were identified: low stable (n=563; 53%), moderate (n=416; 40%), and moderate increasing (n=70; 7%). Women with moderate-increasing SBP were more likely to have delivered preterm compared with those in the low-stable group (40% versus 21%; P<0.0001), and they were more likely to have CAC (38.5% versus 12.2%). The SBP and CAC association varied by preterm birth (P interaction=0.04). Women with preterm delivery and a moderate-increasing SBP had a 2.17-fold higher hazards of CAC (95% confidence interval, 1.14-4.12) compared with women with term births and a lower SBP pattern, adjusted for cardiovascular disease risk factors and other pregnancy features. There was no excess CAC in women with moderate-increasing SBP and term births (adjusted hazard ratio, 1.02; 95% confidence interval, 0.49-2.14). Associations were stronger in women with hypertensive disorders of pregnancy but also detected in those with normotensive preterm deliveries. Women who deliver preterm infants are more likely to follow a high-risk blood pressure pattern throughout the childbearing years that is associated with CAC at midlife.

High-Density Lipoprotein Subspecies Defined by Apolipoprotein C-III and Subclinical Atherosclerosis Measures: MESA (The Multi-Ethnic Study of Atherosclerosis).

BackgroundApolipoprotein C‐III (apoC‐III), a small proinflammatory protein present on 6% to 7% of high‐density lipoprotein (HDL) particles, defines a subspecies of HDL adversely associated with coronary heart disease in primarily white cohorts. In a multi‐ethnic population free of clinical cardiovascular disease, we evaluated the relationship between apoC‐III–defined HDL subspecies and subclinical markers of atherosclerotic pathology.Methods and ResultsWe investigated cross‐sectional associations between apolipoprotein A‐I concentrations of apoC‐III–defined HDL subspecies, measured via ELISA and imaging measures of subclinical atherosclerosis, among 4659 participants in the MESA (The Multi‐Ethnic Study of Atherosclerosis) at baseline (2000–2002). HDL particles containing and lacking apoC‐III were divergently associated with coronary artery calcification in women (P‐heterogeneity=0.002) but not in men (P‐heterogeneity=0.31) and with carotid plaque score (P‐heterogeneity=0.02) and intima‐media thickness (P‐heterogeneity=0.06) in the overall study population. HDL lacking apoC‐III was inversely associated with all outcome measures (coronary artery calcification, women: odds ratio per SD=0.81 [95% confidence interval [CI], 0.73–0.90]; carotid plaque, overall: odds ratio per SD=0.92 [95% CI, 0.84–1.00]; intima‐media thickness, overall: mean difference per SD=−14.0 µm [95% CI, −21.1 to −6.7 μm]), whereas HDL containing apoC‐III was positively associated (coronary artery calcification, women: odds ratio=1.10 [95% CI, 0.99–1.22]; plaque, overall: odds ratio=1.10 [95% CI, 1.01–1.19]) or unassociated. Neither total HDL nor HDL subspecies was associated with changes in subclinical atherosclerosis measures up to 10 years later.ConclusionsThe presence of apoC‐III defined a subspecies of HDL not inversely associated with baseline measures of subclinical atherosclerosis, supporting a role of apoC‐III in the pathophysiology of cardiovascular disease.

Factor VII-activating protease: sex-related association with coronary artery calcification.

: Factor VII-activating protease (FSAP) may regulate development of cardiovascular disease (CVD). We evaluated sex differences in FSAP measures and examined the association between FSAP and coronary artery calcification (CAC) in a middle-aged population. Participants were randomly selected citizens aged 50 or 60 without CVD, diabetes mellitus, Marburg I polymorphism, or hormone replacement therapy (HRT). FSAP protein concentration (total FSAP), FSAP urokinase-activating capacity (FSAP GP), and FSAP GP/total FSAP (specific FSAP activity) were measured. Cardiac computed tomography (CT) determined the Agatston score, dividing the study population in three groups: (1) Agatston score = 0 U, (2) Agatston score = 1-99 U, or (3) Agatston score more than 99 U. A total of 134 women and 116 men were included. Total FSAP, FSAP GP, and specific FSAP activity were independently higher in women (97.4%, 81.1%, 0.84, respectively) compared with men (87.5%, 68.7%, 0.79, respectively) (P < 0.001). In women, total FSAP was significantly different between (3) Agatston score (111.5%) and (1) Agatston score (95.4%), respectively, (2) Agatston score (96.8%), (P < 0.05). Also, the specific activity of FSAP was significantly different between (3) Agatston score (0.77) and (1) Agatston score (0.85), respectively, (2) Agatston score (0.86) (P < 0.05). No difference in FSAP measures was observed in men. FSAP measures are higher in women compared with age-matched men. The extent of CAC in women is positively associated with total FSAP, but negatively associated with the specific activity of FSAP suggesting that FSAP may play a role in the evolution of CVD in women.

Serum cystatin C levels are associated with coronary artery calcification in women without chronic kidney disease

BackgroundChronic renal disease (CKD) is a determinant of coronary artery calcification (CAC), which is a predictor of cardiovascular events. However, in a population without CKD, the association between CAC and renal function is unclear. CAC is affected by sex. This study aimed to determine whether serum cystatin C, a sensitive marker of kidney function, or sex differences are associated with CAC in patients without CKD. MethodsWe evaluated 456 consecutive patients (61±13 years, 42% women) without CKD and evidence of coronary artery disease. The CAC (Agatston) score was examined by multidetector computed tomography. ResultsWhen patients were categorized into three CAC groups based on the Agatston score, mild (<10), moderate (11–399), and severe (≥400) in each sex, serum cystatin C levels gradually increased by severity of CAC in women, but not men. Receiver operating characteristic curve analysis showed that, in women, a cut-off value of 0.97mg/l for cystatin C discriminated patients with severe CAC with a sensitivity of 71% and specificity of 77% (area under the curve, 0.74; 95% CI: 0.62–0.86; p<0.01). Multivariate logistic analysis showed that serum cystatin C was not associated with severe CAC in all patients and men, but this association was observed in women (OR: 7.80 for cystatin C≥0.97mg/l, 95% CI: 1.76–34.6, p<0.01). ConclusionHigher serum cystatin C levels are associated with greater CAC in women without CKD. Measurement of cystatin C may be useful for identifying women who are at high risk for cardiovascular disease.