Thoracic versus coronary calcification for atherosclerotic cardiovascular disease events prediction.

This study compared the prognostic value of quantified thoracic artery calcium (TAC) including aortic arch on chest CT and coronary artery calcium (CAC) score on ECG-gated cardiac CT. METHODS: A total of 2412 participants who underwent both chest CT and ECG-gated cardiac CT at the same period were included in the Multi-Ethnic Study of Atherosclerosis Exam 5. All participants were monitored for incident atherosclerotic cardiovascular disease (ASCVD) events. TAC is defined as calcification in the ascending aorta, aortic arch and descending aorta on chest CT. The quantification of TAC was measured using the Agatston method. Time-dependent receiver-operating characteristic (ROC) curves were used to compare the prognostic value of TAC and CAC scores. RESULTS: Participants were 69±9 years of age and 47% were male. The Spearman correlation between TAC and CAC scores was 0.46 (p<0.001). During the median follow-up period of 8.8 years, 234 participants (9.7%) experienced ASCVD events. In multivariable Cox regression analysis, TAC score was independently associated with increased risk of ASCVD events (HR 1.31, 95% CI 1.09 to 1.58) as well as CAC score (HR 1.82, 95% CI 1.53 to 2.17). However, the area under the time-dependent ROC curve for CAC score was greater than that for TAC score in all participants (0.698 and 0.641, p=0.031). This was particularly pronounced in participants with borderline/intermediate and high 10-year ASCVD risk scores. CONCLUSION: Our study demonstrated a significant association between TAC and CAC scores but a superior prognostic value of CAC score for ASCVD events. These findings suggest TAC on chest CT provides supplementary data to estimate ASCVD risk but does not replace CAC on ECG-gated cardiac CT.

Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies.

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium. METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction. RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions. CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.

Prevalence of Aortic Valve Calcium and the Long-Term Risk of Incident Severe Aortic Stenosis.

BACKGROUND: Aortic valve calcification (AVC) is a principal mechanism underlying aortic stenosis (AS). OBJECTIVES: This study sought to determine the prevalence of AVC and its association with the long-term risk for severe AS. METHODS: Noncontrast cardiac computed tomography was performed among 6,814 participants free of known cardiovascular disease at MESA (Multi-Ethnic Study of Atherosclerosis) visit 1. AVC was quantified using the Agatston method, and normative age-, sex-, and race/ethnicity-specific AVC percentiles were derived. The adjudication of severe AS was performed via chart review of all hospital visits and supplemented with visit 6 echocardiographic data. The association between AVC and long-term incident severe AS was evaluated using multivariable Cox HRs. RESULTS: AVC was present in 913 participants (13.4%). The probability of AVC >0 and AVC scores increased with age and were generally highest among men and White participants. In general, the probability of AVC >0 among women was equivalent to men of the same race/ethnicity who were approximately 10 years younger. Incident adjudicated severe AS occurred in 84 participants over a median follow-up of 16.7 years. Higher AVC scores were exponentially associated with the absolute risk and relative risk of severe AS with adjusted HRs of 12.9 (95% CI: 5.6-29.7), 76.4 (95% CI: 34.3-170.2), and 380.9 (95% CI: 169.7-855.0) for AVC groups 1 to 99, 100 to 299, and ≥300 compared with AVC = 0. CONCLUSIONS: The probability of AVC >0 varied significantly by age, sex, and race/ethnicity. The risk of severe AS was exponentially higher with higher AVC scores, whereas AVC = 0 was associated with an extremely low long-term risk of severe AS. The measurement of AVC provides clinically relevant information to assess an individual's long-term risk for severe AS.

Association Between Omega-3 Fatty Acid Levels and Aortic Valve Calcium (from the Multi-Ethnic Study of Atherosclerosis).

Calcific aortic valve disease, a condition of chronic inflammation, is associated with increased cardiovascular events and all-cause mortality. Omega-3 fatty acids (O3FAs) reduce both acute and chronic inflammation, but their associations with aortic valve calcium (AVC) have not been studied. The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of 6,814 adults without clinical cardiovascular disease. Plasma fatty acid levels and cardiac computed tomography (CT) scans were performed at baseline, and CT scans were performed at subsequent clinical visits over a median 9-year period. We assessed whether plasma levels of O3FAs and their species correlate with the presence, severity, and progression of AVC measured by CT in Multi-Ethnic Study of Atherosclerosis. The mean age of the 6,510 included participants with baseline fatty acid levels, AVC, and covariate data was 62.1 ± 10.2 years, and 47.1% of the participants were male. Race distribution was 38.6% White, 27.2% Black, 22.1% Hispanic/Latino, and 12.1% Chinese. Among the 6,510 participants, 5,884 had a subsequent CT scan, and 3,304 had a third CT scan with AVC measurements. At baseline, 862 participants (13.2%) had prevalent AVC (Agatston score >0), and were more likely to be of older age, male, of the White race, have a lower education level, and have co-morbidities that are associated with a higher risk for AVC. Plasma tertiles of eicosapentaenoic acid, docosahexaenoic acid, and total O3FA were not associated with prevalent AVC at baseline, incident AVC, or change in AVC. In conclusion, plasma levels of O3FAs in subjects not routinely supplemented with O3FAs are not useful for predicting the presence or development of AVC. Whether high plasma O3FA levels, achievable by high-dose O3FA over-the-counter supplementation or pharmacotherapy, is associated with AVC requires further investigation.

Serum vitamin D and sex hormones levels in men and women: The Multi-Ethnic Study of Atherosclerosis (MESA).

INTRODUCTION: 25-hydroxyvitamin D [25(OH)D] deficiency has been associated with low testosterone levels in men, but there are conflicting reports of its associations with sex hormones in women. Less is known about whether these associations are independent of adiposity and lifestyle factors, and whether they differ by race/ethnicity. AIM: To examine associations of 25(OH)D concentrations with sex hormone levels. METHODS: Cross-sectional analysis of 3017 men and 2929 women in a multi-ethnic cohort. MAIN OUTCOME MEASURES: Testosterone, estradiol, dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and free testosterone. RESULTS: The mean (SD) levels of 25(OH)D in men and women were 25.7(10.4) and 26.1(12.0)ng/ml, respectively. In men, after adjusting for demographic and lifestyle variables, a 10ng/ml [25nmol/L] decrease in 25(OH)D was associated with an average difference of -0.70nmol/L (95%CI -1.36, -0.05) in SHBG and 0.02 percent (0.01, 0.04) in free testosterone, but was not associated with low total testosterone level (<10.41nmol/L). In women, a 10ng/ml decrease in 25(OH)D levels was associated with an average difference of -0.01nmol/L (-0.01, -0.00) for estradiol, -8.29nmol/L (-10.13, -6.45) for SHBG, 0.06 percent (0.04, 0.07) for free testosterone, and 0.40nmol/L (0.19, 0.62) for DHEA. There was no significant interaction by race/ethnicity. CONCLUSIONS: Lower 25(OH)D concentrations were associated with lower SHBG levels and higher free testosterone levels in both men and women, and lower estradiol and higher DHEA levels in women, independent of adiposity and lifestyle. We observed no significant association of 25(OH)D with total testosterone in men. Future studies are needed to determine whether vitamin D supplementation influences sex hormone levels.

Associations of Coffee, Tea, and Caffeine Intake with Coronary Artery Calcification and Cardiovascular Events.

BACKGROUND: Coffee and tea are 2 of the most commonly consumed beverages in the world. The association of coffee and tea intake with coronary artery calcium and major adverse cardiovascular events remains uncertain. METHODS: We examined 6508 ethnically diverse participants with available coffee and tea data from the Multi-Ethnic Study of Atherosclerosis. Intake for each was classified as never, occasional (<1 cup per day), and regular (≥1 cup per day). A coronary artery calcium progression ratio was derived from mixed effect regression models using loge(calcium score+1) as the outcome, with coefficients exponentiated to reflect coronary artery calcium progression ratio versus the reference. Cox proportional hazards analyses were used to evaluate the association between beverage intake and incident cardiovascular events. RESULTS: Over a median follow-up of 5.3 years for coronary artery calcium and 11.1 years for cardiovascular events, participants who regularly drank tea (≥1 cup per day) had a slower progression of coronary artery calcium compared with never drinkers after multivariable adjustment. This correlated with a statistically significant lower incidence of cardiovascular events for ≥1 cup per day tea drinkers (adjusted hazard ratio 0.71; 95% confidence interval 0.53-0.95). Compared with never coffee drinkers, regular coffee intake (≥1 cup per day) was not statistically associated with coronary artery calcium progression or cardiovascular events (adjusted hazard ratio 0.97; 95% confidence interval 0.78-1.20). Caffeine intake was marginally inversely associated with coronary artery calcium progression. CONCLUSIONS: Moderate tea drinkers had slower progression of coronary artery calcium and reduced risk for cardiovascular events. Future research is needed to understand the potentially protective nature of moderate tea intake.

Metal mixtures in urban and rural populations in the US: The Multi-Ethnic Study of Atherosclerosis and the Strong Heart Study.

BACKGROUND: Natural and anthropogenic sources of metal exposure differ for urban and rural residents. We searched to identify patterns of metal mixtures which could suggest common environmental sources and/or metabolic pathways of different urinary metals, and compared metal-mixtures in two population-based studies from urban/sub-urban and rural/town areas in the US: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Strong Heart Study (SHS). METHODS: We studied a random sample of 308 White, Black, Chinese-American, and Hispanic participants in MESA (2000-2002) and 277 American Indian participants in SHS (1998-2003). We used principal component analysis (PCA), cluster analysis (CA), and linear discriminant analysis (LDA) to evaluate nine urinary metals (antimony [Sb], arsenic [As], cadmium [Cd], lead [Pb], molybdenum [Mo], selenium [Se], tungsten [W], uranium [U] and zinc [Zn]). For arsenic, we used the sum of inorganic and methylated species (∑As). RESULTS: All nine urinary metals were higher in SHS compared to MESA participants. PCA and CA revealed the same patterns in SHS, suggesting 4 distinct principal components (PC) or clusters (∑As-U-W, Pb-Sb, Cd-Zn, Mo-Se). In MESA, CA showed 2 large clusters (∑As-Mo-Sb-U-W, Cd-Pb-Se-Zn), while PCA showed 4 PCs (Sb-U-W, Pb-Se-Zn, Cd-Mo, ∑As). LDA indicated that ∑As, U, W, and Zn were the most discriminant variables distinguishing MESA and SHS participants. CONCLUSIONS: In SHS, the ∑As-U-W cluster and PC might reflect groundwater contamination in rural areas, and the Cd-Zn cluster and PC could reflect common sources from meat products or metabolic interactions. Among the metals assayed, ∑As, U, W and Zn differed the most between MESA and SHS, possibly reflecting disproportionate exposure from drinking water and perhaps food in rural Native communities compared to urban communities around the US.

Serum 25-hydroxyvitamin D, calcium, phosphorus, and electrocardiographic QT interval duration: findings from NHANES III and ARIC.

CONTEXT: Disturbances in 25-hydroxyvitamin D, calcium, and phosphorus concentrations have been associated with increased risks of total and cardiovascular mortality. It is possible that changes in electrocardiographic QT interval duration may mediate these effects, but the association of 25-hydroxyvitamin D, phosphorus, and calcium concentrations with QT interval duration has not been evaluated in general population samples. OBJECTIVE: The objective of the study was to evaluate the association of 25-hydroxyvitamin D, phosphorus, and calcium concentrations with QT interval duration in two large samples of the U.S. general population. DESIGN: This study included cross-sectional analyses the Third National Health and Nutrition Survey (NHANES III) and the Atherosclerosis Risk in Communities (ARIC) study. SETTING: The study was conducted in the general community. PATIENTS OR OTHER PARTICIPANTS: Patients included 7,312 men and women from NHANES III and 14,825 men and women from the ARIC study. INTERVENTIONS: Serum 25-hydroxyvitamin D, total and ionized calcium, and inorganic phosphorus were measured in NHANES III, and serum total calcium and inorganic phosphorus were measured in ARIC. MAIN OUTCOME MEASURE: QT interval duration was obtained from standard 12-lead electrocardiograms. RESULTS: In NHANES III, the multivariate adjusted differences in average QT interval duration comparing the highest vs. the lowest quartiles of serum total calcium, ionized calcium, and phosphorus were -3.6 msec (-5.8 to -1.3; P for trend = 0.005), -5.4 msec (-7.4 to -3.5; P for trend <0.001), and 3.9 msec (2.0-5.9; P for trend <0.001), respectively. The corresponding differences in ARIC were -3.1 msec (-4.3 to -2.0; P for trend <0.001), -2.9 msec (-3.8 to -1.9; P for trend <0.001), and 2.3 msec (1.3-3.3; P for trend <0.001). No association was found between 25-hydroxyvitamin D concentrations and QT interval duration. CONCLUSIONS: In two large samples of the general population, QT interval duration was inversely associated with the serum total and ionized calcium and positively associated with serum phosphorus.

Coffee, alcohol, smoking, physical activity and QT interval duration: results from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Abnormalities in the electrocardiographic QT interval duration have been associated with an increased risk of ventricular arrhythmias and sudden cardiac death. However, there is substantial uncertainty about the effect of modifiable factors such as coffee intake, cigarette smoking, alcohol consumption, and physical activity on QT interval duration. METHODS: We studied 7795 men and women from the Third National Health and Nutrition Survey (NHANES III, 1988-1994). Baseline QT interval was measured from the standard 12-lead electrocardiogram. Coffee and tea intake, alcohol consumption, leisure-time physical activities over the past month, and lifetime smoking habits were determined using validated questionnaires during the home interview. RESULTS: In the fully adjusted model, the average differences in QT interval comparing participants drinking ≥6 cups/day to those who did not drink any were -1.2 ms (95% CI -4.4 to 2.0) for coffee, and -2.0 ms (-11.2 to 7.3) for tea, respectively. The average differences in QT interval duration comparing current to never smokers was 1.2 ms (-0.6 to 2.9) while the average difference in QT interval duration comparing participants drinking ≥7 drinks/week to non-drinkers was 1.8 ms (-0.5 to 4.0). The age, race/ethnicity, and RR-interval adjusted differences in average QT interval duration comparing men with binge drinking episodes to non-drinkers or drinkers without binge drinking were 2.8 ms (0.4 to 5.3) and 4.0 ms (1.6 to 6.4), respectively. The corresponding differences in women were 1.1 (-2.9 to 5.2) and 1.7 ms (-2.3 to 5.7). Finally, the average differences in QT interval comparing the highest vs. the lowest categories of total physical activity was -0.8 ms (-3.0 to 1.4). CONCLUSION: Binge drinking was associated with longer QT interval in men but not in women. QT interval duration was not associated with other modifiable factors including coffee and tea intake, smoking, and physical activity.