Leukocyte telomere length and cardiovascular disease in African Americans: The Jackson Heart Study.
ABSTRACT: BACKGROUND AND AIMS:In European descent populations, shorter leukocyte telomere length (LTL) has been associated with subclinical atherosclerosis, cardiovascular disease (CVD), and mortality, while longer LTL has been associated with greater left ventricular hypertrophy. We evaluated the relationship of LTL with subclinical cardiovascular disease indices and incident clinical events and mortality in African Americans (AAs). METHODS:Analyses were restricted to 2518 participants of the Jackson Heart Study (JHS) with LTL measured by Southern blot in baseline blood samples. RESULTS:Adjusting for established CVD risk factors, longer LTL was significantly associated with lower prevalence of coronary artery calcification (CAC) (odds ratio (OR) = 0.810) per 1 kb increase in LTL; (95% confidence interval [CI] 0.656, 0.9998), p=0.0498). Longer LTL was also associated with higher ankle brachial index (ABI) (? = 0.023; (95% CI 0.004, 0.042), p=0.017) when comparing the highest to the lowest LTL quartile. There were no significant associations between LTL and abdominal aortic calcification, carotid intima-media thickness, or left ventricular mass. After a median follow-up of 9 years, longer LTL was associated with lower risk of incident ischemic stroke (hazard ratio (HR) 0.69 (95% CI 0.48, 0.99), p=0.044) and total mortality (HR 0.81 (95% CI 0.67, 0.97), p=0.026) in age and sex adjusted models, but these associations were no longer significant in fully adjusted models. CONCLUSIONS:Among a community-based cohort of AAs, longer LTL was nominally associated with lower odds of CAC and increased ABI, indicative of decreased prevalence of subclinical atherosclerosis and peripheral arterial disease. These findings do not offer strong support for LTL as an independent biomarker of CVD risk in AAs.
Project description:Circulating adiponectin is associated with both clinical and subclinical cardiovascular disease (CVD). Variants of the adiponectin gene (ADIPOQ) are associated with clinical CVD, but little is known about associations with subclinical CVD. We studied the association of 11 ADIPOQ single-nucleotide polymorphisms (SNPs) with common and internal carotid intima media thickness (cIMT), presence of coronary artery calcification (CAC), and CAC scores (in those with CAC) in 2,847 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were white (n = 712), African American (n = 712), Chinese (n = 718), and Hispanic (n = 705). All models were adjusted for age, sex, and field site, and stratified by race/ethnic group. African Americans with genotypes AG/GG of rs2241767 had 36% greater (95% confidence interval (CI; 16%, 59%), P = 0.0001) CAC prevalence; they also had a larger common cIMT (P = 0.0043). Also in African Americans, genotypes AG/AA of rs1063537 were associated with a 35% (95% CI (14%, 59%), P = 0.0005) greater CAC prevalence. Hispanics with the AA genotype of rs11711353 had a 37% (95% CI (14%, 66%), P = 0.0011), greater CAC prevalence compared to those with the GG genotype. Additional adjustment for ancestry in African-American and Hispanic participants did not change the results. No single SNP was associated with subclinical CVD phenotypes in Chinese or white participants. There appears to be an association between ADIPOQ SNPs and subclinical CVD in African Americans and Hispanics. Replication as well as assessment of other ADIPOQ SNPs is warranted.
Project description:Coronary artery calcification (CAC) is a strong predictor of atherosclerotic cardiovascular disease (CVD). Whites appear to have a higher prevalence of CAC than African-Americans (AAs), but it is unknown if type 2 diabetes, a major cardiovascular risk factor, attenuates this difference. We investigated the relationship of race and CAC in a sample of patients with type 2 diabetes without clinical CVD.multivariable analyses of self-reported ethnicity and CAC scores, stratified by gender, in 861 subjects [32% AA, 66.9% male] with type 2 diabetes.AA race was associated with lower CAC scores in age-adjusted models in males [Tobit ratio for AAs vs. Whites 0.14 (95% CI 0.08-0.24, p<0.001)] and females [Tobit ratio 0.26 (95% CI 0.09-0.77, p=0.015)]. This persisted in men after adjustment for traditional, metabolic and inflammatory risk factors, but adjustment for plasma triglycerides [0.48 (95% CI 0.15-1.49, p=0.201)] and HOMA-IR [0.28 (95% CI 0.08-1.03, p=0.055)] partially attenuated the association in women.relative to African-Americans, White race is a strong predictor of CAC, even in the presence of type 2 diabetes. The relationship in women appears less robust possibly due to gender differences in metabolic risk factors.
Project description:We reviewed published MESA (Multi-Ethnic Study of Atherosclerosis) study articles concerning peripheral arterial disease, subclavian stenosis (SS), abdominal aortic calcium (AAC), and thoracic artery calcium (TAC). Important findings include, compared to non-Hispanic whites, lower ankle-brachial index (ABI) and more SS in African Americans, and higher ABI and less SS in Hispanic and Chinese Americans. Abnormal ABI and brachial pressure differences were associated with other subclinical cardiovascular disease (CVD) measures. Both very high and low ABI independently predicted increased CVD events. Looking at aortic measures, TAC and AAC were significantly associated with other subclinical CVD measures. Comparisons of AAC with coronary artery calcium (CAC) showed that both were less common in ethnic minority groups. However, although CAC was much more common in men than in women in multivariable analysis, this was not true of AAC. Also, when AAC and CAC were adjusted for each other in multivariable analysis, there was a stronger association for AAC than for CAC with CVD and total mortality.
Project description:Abdominal aortic calcification (AAC) is a measure of subclinical cardiovascular disease (CVD). Data are limited regarding its relation to other measures of atherosclerosis.Among 1812 subjects (49% female, 21% black, 14% Chinese, and 25% Hispanic) within the population-based Multiethnic Study of Atherosclerosis, we examined the cross-sectional relation of AAC with coronary artery calcium (CAC), ankle brachial index (ABI), and carotid intimal medial thickness (CIMT), as well as multiple measures of subclinical CVD.AAC prevalence ranged from 34% in those aged 45-54 to 94% in those aged 75-84 (p < 0.0001), was highest in Caucasians (79%) and lowest in blacks (62%) (p < 0.0001). CAC prevalence, mean maximum CIMT ? 1mm, and ABI < 0.9 was greater in those with vs. without AAC: CAC 60% vs. 16%, CIMT 38% vs. 7%, and ABI 5% vs. 1% for women and CAC 80% vs. 37%, CIMT 43% vs. 16%, and ABI 4% vs. 2% for men (p < 0.01 for all except p < 0.05 for ABI in men). The substantially greater prevalence for CAC in men compared to women all ages is not seen for AAC. By age 65, 97% of men and 91% of women have AAC, CAC, increased CIMT, and/or low ABI. The presence of multi-site atherosclerosis (? 3 of the above) ranged from 20% in women to 30% in men (p < 0.001), was highest in Caucasians (28%) and lowest in Chinese (16%) and ranged from 5% in those aged 45-54 to 53% in those aged 75-84 (p < 0.01 to p < 0.001). Finally, increased AAC was associated with 2-3-old relative risks for the presence of increased CIMT, low ABI, or CAC.AAC is associated with an increased likelihood of other vascular atherosclerosis. Its additive prognostic value to these other measures is of further interest.
Project description:Introduction:Magnesium (Mg) may protect against arterial calcification. We tested the hypotheses that a higher serum Mg concentration is associated with less arterial calcification and stiffness in patients on hemodialysis (HD) and that these associations are modified by diabetes mellitus. Methods:We performed cross-sectional analyses of 367 incident HD patients from the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) cohort. Measures of arterial calcification and stiffness included coronary arterial calcification (CAC) and thoracic aortic calcification (TAC) scores, ankle brachial index (ABI; high ABI: >1.4 or incompressible vessels), pulse wave velocity (PWV), and pulse pressure. Results:Mean Mg was 1.8 ± 0.2 mEq/l and 58% had diabetes. Among nondiabetic individuals, per 0.1 mEq/l higher Mg, non-zero CAC score was lower (% difference: -15.4%; 95% confidence interval [CI]: -28% to -0.55%; P = 0.03), the odds of having TAC score >0 and the odds of having high ABI were lower (odds ratio [OR]: 0.66; 95% CI 0.47-0.93; P = 0.02, and 0.23; 95% CI: 0.06-0.83, P = 0.03, respectively) while adjusting for demographics, comorbidities, markers of mineral metabolism, and dialysis clearance. Among diabetic individuals, per 0.1 mEq/l higher Mg, the odds of having TAC score >0 was higher (OR: 1.57; 95% CI: 1.09-2.26; P = 0.02). Mg was not associated with CAC or high ABI among diabetic individuals. Mg was not associated with PWV or pulse pressure regardless of diabetes status. Conclusion:Diabetes modified the associations of serum Mg with arterial calcification and stiffness in incident HD patients. Higher Mg was associated with less arterial calcification and less peripheral arterial stiffness among nondiabetic individuals, but Mg was only associated with TAC among diabetic individuals with higher Mg being associated with higher likelihood of having TAC score >0.
Project description:Aims:The aim is to investigate (multifocal) cardiovascular calcification in patients with established cardiovascular disease (CVD), regarding prevalence, risk factors, and relation with recurrent CVD or vascular interventions. Coronary artery calcification (CAC), thoracic aortic calcification (TAC) (including ascending aorta, aortic arch, descending aorta), mitral annular calcification (MAC), and aortic valve calcification (AVC) are studied. Methods:The study concerned 568 patients with established CVD enrolled in the ORACLE cohort. All patients underwent computed tomography. Prevalence of site-specific and multifocal calcification was determined. Ordinal regression analyses were performed to quantify associations of risk factors with cardiovascular calcification, and Cox regression analyses to determine the relation between calcium scores and recurrent CVD or vascular interventions. Results:Calcification was multifocal in 76% (N = 380) of patients with calcification. Age (per SD) was associated with calcification at all locations (lowest OR 2.17; 99%CI 1.54-3.11 for ascending aorta calcification). Diabetes mellitus and systolic blood pressure were associated with TAC, whereas male sex was a determinant of CAC. TAC and CAC were related to the combined endpoint CVD or vascular intervention (N = 68). In a model with all calcium scores combined, only CAC was related to the combined outcome (HR 1.39; 95%CI 1.15-1.68). Conclusion:Cardiovascular calcification is generally multifocal in patients with established CVD. Differences in associations between risk factors and calcification at various anatomical locations stress the divergence in pathophysiological pathways. CAC is most strongly related to recurrent CVD or vascular interventions independent of traditional risk factors, and independent of heart valve and thoracic aorta calcification.
Project description:Low-density lipoprotein particle (LDL-P) has recently been found to be a stronger predictor of cardiovascular disease (CVD) than LDL-cholesterol (LDL-C).Whether LDL-P is associated with subclinical atherosclerosis, independent of LDL-C, as well as other lipid measures has not been fully examined. We aimed to analyze LDL-P associations with measures of subclinical atherosclerosis.We examined 870 Japanese men randomly selected from Kusatsu City, Shiga, Japan, aged 40-79 years from 2006-2008, free of clinical CVD and not using lipid-lowering medication. Cross-sectional associations of lipid measures with carotid intima-media thickness (cIMT) and coronary artery calcification (CAC; >0 Agatston score) were examined.LDL-P was significantly positively associated with cIMT and maintained this association after adjustments for LDL-C and other lipid measures. Although these lipid measures were positively associated with cIMT, model adjustment for LDL-P removed any significant relationships. Higher LDL-P was associated with a significantly higher odds ratio of CAC and further adjustment for LDL-C did not affect this relationship. In contrast, the LDL-C association with CAC was no longer significant after adjustment for LDL-P. Other lipid measures attenuated associations of LDL-P with CAC. Likewise, associations of these measures with CAC were attenuated when model adjustments for LDL-P were made.In a community-based sample of Japanese men, free of clinical CVD, LDL-P was a robust marker for subclinical atherosclerosis, independent of LDL-C and other lipid measures. Associations of LDL-C and other lipid measures with either cIMT or CAC were generally not independent of LDL-P.
Project description:Long working hours may be associated with cardiovascular disease (CVD). The objective was to investigate cross-sectional associations of work hours with carotid intima-media thickness (CIMT) and ankle-brachial index (ABI).Participants were 1694 women and 1868 men from the Multi-Ethnic Study of Atherosclerosis. CIMT and ABI were measured using standard protocols. Information on work hours was obtained from questionnaires. Mean values of CIMT and ABI were examined across five categories of hours worked per week (?20, 21-39, 40, 41-50 and >50) using analysis of variance/analysis of covariance. p Values for trend were obtained from linear regression models.Mean age of participants was 56.9±8.4 years; 52.4% were men. Distinct patterns of association between work hours and the subclinical CVD biomarkers were found for women and men, although this heterogeneity by gender was not statistically significant. Among women only, work hours were positively associated with common (but not internal) CIMT (p=0.073) after full risk factor adjustment. Compared with women working 40 h, those working >50 h were more likely to have an ABI <1 (vs 1-1.4) (OR=1.85, 95% CI 1.01 to 3.38). In men, work hours and ABI were inversely associated (p=0.046). There was some evidence that the association between work hours and ABI was modified by occupational category (interaction p=0.061). Among persons classified as management/professionals, longer work hours was associated with lower ABI (p=0.015). No significant associations were observed among other occupational groups.Working longer hours may be associated with subclinical CVD. These associations should be investigated using longitudinal studies.
Project description:Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less clear.To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD).Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up.The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated.Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio [HR], 0.85; 95% CI, 0.80-0.91; P?<?.001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P?=?.002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (??=?-0.24; 95% CI, -0.45 to -0.03; P?=?.02) and significantly better lobal longitudinal strain (??=?-0.09; 95% CI, -0.14 to -0.05; P?<?.001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P?=?.002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P?=?.006), respectively, along with a more impaired strain (??=?0.15; 95% CI, 0.08-0.23; P?<?.001). No association between change in fitness and CAC was found.Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.
Project description:BACKGROUND AND AIMS:CVD risks associated with coronary artery calcification (CAC) and aortic calcification (AC) are well known, but less is known about other calcified arteries. We aimed to assess the associations of arterial calcification in the breast, splenic, and internal and external iliac arteries with CVD risk factors and mortality. METHODS:We conducted a case-cohort study nested in a cohort of 5196 individuals who self-referred or were referred by a health care provider for whole body computed tomography (CT), including a random subcohort (n = 395) and total and CVD mortality cases (n = 298 and n = 90), who died during a median follow-up of 9.4 years. Arterial calcification in the breast, splenic, and internal and external iliac arteries on CT was scored using a simple visual score. AC and CAC were previously measured using the Agatston technique. Logistic regression models were made to study associations of CVD risk factors with calcification in the different vascular beds. Prentice-weighted Cox proportional hazards models adjusted for CVD risk factors, and calcification in other vascular beds, were used to study associations with mortality. RESULTS:In the subcohort, the mean age was 56.6 years (SD 11.1) and 41.3% were female. The prevalence of calcification on CT, was 11.6% in the splenic, 47.9% in the internal iliac and 9.5% in the external iliac arteries, while 3.7% of women had breast artery calcification (BAC). Calcification in the splenic and iliac arteries was associated with calcification in the abdominal aorta but differentially associated with other CVD risk factors in logistic regression models. The prevalence of BAC was too low to fit these multivariable models. Calcification of the external iliac arteries was significantly associated with both all-cause and CVD mortality, but no longer significant when adjusted for CVD risk factors. Breast artery calcification was associated with both all-cause and CVD mortality independent of CVD risk factors and AAC and CAC (all-cause HR 5.67 [95% CI 1.50-21.41]). CONCLUSIONS:Risk factors associated with calcification, and the association of calcification with risk of mortality differ across vascular beds, possibly reflecting different pathophysiology.