Abstract Background The improvement in discrimination gained by adding nontraditional cardiovascular risk markers cited in the 2013 American College of Cardiology/American Heart Association ...cholesterol guidelines to the atherosclerotic cardiovascular disease (ASCVD) risk estimator (pooled cohort equation PCE) is untested. Objectives This study assessed the predictive accuracy and improvement in reclassification gained by the addition of the coronary artery calcium (CAC) score, the ankle–brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) levels, and family history (FH) of ASCVD to the PCE in participants of MESA (Multi-Ethnic Study of Atherosclerosis). Methods The PCE was calibrated (cPCE) and used for this analysis. The Cox proportional hazards survival model, Harrell’s C statistics, and net reclassification improvement analyses were used. ASCVD was defined as myocardial infarction, coronary heart disease–related death, or fatal or nonfatal stroke. Results Of 6,814 MESA participants not prescribed statins at baseline, 5,185 had complete data and were included in this analysis. Their mean age was 61 years; 53.1% were women, 9.8% had diabetes, and 13.6% were current smokers. After 10 years of follow-up, 320 (6.2%) ASCVD events occurred. CAC score, ABI, and FH were independent predictors of ASCVD events in the multivariable Cox models. CAC score modestly improved the Harrell’s C statistic (0.74 vs. 0.76; p = 0.04); ABI, hsCRP levels, and FH produced no improvement in Harrell’s C statistic when added to the cPCE. Conclusions CAC score, ABI, and FH were independent predictors of ASCVD events. CAC score modestly improved the discriminative ability of the cPCE compared with other nontraditional risk markers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives The purpose of this study was to examine the association of both a low and a high ankle-brachial index (ABI) with incident cardiovascular events in a multiethnic cohort. Background ...Abnormal ABIs, both low and high, are associated with elevated cardiovascular disease (CVD) risk. However, it is unknown whether this association is consistent across different ethnic groups, and whether it is independent of both newer biomarkers and other measures of subclinical atherosclerotic CVD. Methods A total of 6,647 non-Hispanic white, African-American, Hispanic, and Chinese men and women age 45 to 84 years from free-living populations in 6 U.S. field centers and free of clinical CVD at baseline had extensive measures of traditional and newer biomarker risk factors, and measures of subclinical CVD, including the ABI. Incident CVD, defined as coronary disease, stroke, or other atherosclerotic CVD death, was determined over a mean follow-up of 5.3 years. Results Both a low (<1.00) and a high (≥1.40) ABI were associated with incident CVD events. Sex- and ethnic-specific analyses showed consistent results. Hazard ratios were 1.77 (p < 0.001) for a low and 1.85 (p = 0.050) for a high ABI after adjustment for both traditional and newer biomarker CVD risk factors, and the ABI significantly improved risk discrimination. Further adjustment for coronary artery calcium score, common and internal carotid intimal medial thickness, and major electrocardiographic abnormalities only modestly attenuated these hazard ratios. Conclusions In this study, both a low and a high ABI were associated with elevated CVD risk in persons free of known CVD, independent of standard and novel risk factors, and independent of other measures of subclinical CVD. Further research should address the cost effectiveness of measuring the ABI in targeted population groups.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Elevated coronary artery calcium (CAC) is a marker for increase risk of coronary heart disease (CHD). Although most CHD events occur among individuals with advanced CAC, CHD can also occur ...in individuals with little or no calcified plaque. In this study, we sought to evaluate the characteristics associated with incident CHD events in the setting of minimal (score ≤10) or absent CAC (score of zero). Methods Asymptomatic participants in the MESA (N = 6,809) were followed for occurrence of all CHD events (including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death) and hard CHD events (myocardial infarction or CHD death). Time to incident CHD was modeled using age-and gender-adjusted Cox regression. Results The final study population consisted of 3,923 MESA asymptomatic participants (mean age 58 ± 9 years, 39% males) who had CAC scores of 0 to 10. Overall, no detectable CAC was seen in 3415 individuals, whereas 508 had CAC scores of 1 to 10. During follow-up (median 4.1 years), there were 16 incident hard events and 28 all CHD events in individuals with absent or minimal CAC. In age-, gender-, race-, and CHD risk factor-adjusted analysis, minimal CAC (1-10) was associated with an estimated 3-fold greater risk of a hard CHD event (HR 3.23, 95% CI 1.17-8.95) or of all CHD event (HR 3.66, 95% CI 1.71-7.85) compared to those with CAC = 0. Former smoking (HR 3.57, 95% CI 1.08-11.77), current smoking (HR 4.93, 95% CI 1.20-20.30), and diabetes (HR 3.09, 95% CI 1.07-8.93) were significant risk factors for events in those with CAC = 0. Conclusion Asymptomatic persons with absent or minimal CAC are at very low risk of future cardiovascular events. Individuals with minimal CAC (1-10) were significantly increased to 3-fold increased risk for incident CHD events relative to those with CAC scores of zero.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective Several studies report a higher prevalence of peripheral arterial disease (PAD) in women and among blacks. These studies based their PAD definition on an ankle-brachial index (ABI) <0.90. ...We hypothesized that there is an inherent contribution of gender and ethnicity to normal ABI values, independent of biologic and social disparities that exist between gender and ethnic groups. Consequently, an ABI threshold that disregards these fundamental gender-related and ethnicity-related differences could partly contribute to reported prevalence differences. Methods A cross-sectional study was designed as part of the Multi-Ethnic Study of Atherosclerosis (MESA), a multicenter United States population study. We selected a subgroup of participants with unequivocally normal ABIs (1.00 to 1.30), and additionally excluded participants with any major PAD risk factor (smoking, diabetes, dyslipidemia, hypertension). In a linear model with ABI as the dependent variable, demographic, clinical, biologic, and social variables were introduced as independent factors. Results Among 1775 healthy participants, there was no association between ABI level and subclinical cardiovascular disease (coronary calcium or carotid plaque). Male gender, weight, and high education level were positively correlated with ABI, whereas black race, triglycerides, pack-years (in past smokers), and pulse pressure were negatively correlated. In the fully adjusted model, women had about 0.02 lower ABI values than men, and blacks showed ABI values about 0.02 lower than non-Hispanic whites. Conclusion These data suggest intrinsic ethnic and gender differences in ABI. Such differences, although small in magnitude, are highly significant and can distort population estimates of disease burden.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
It has been proposed that coronary artery calcium (CAC) can be used to estimate arterial age in adults. Supporting this concept is that chronologic age, as used in cardiovascular risk assessment, is ...a surrogate for atherosclerotic burden. This measure can provide patients with a more understandable version of their CAC scores (e.g., “You are 55 years old, but your arteries are more consistent with an arterial age of 65 years”). The aim of this study was to describe a method of calculating arterial age by equating estimated coronary heart disease (CHD) risk for observed age and CAC. Arterial age is then the risk equivalent of CAC. Data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of 6,814 participants free of clinical cardiovascular disease and followed for an average of 4 years, were used. Estimated arterial age was obtained as a simple linear function of log-transformed CAC. In a model for incident CHD risk controlling for age and arterial age, only arterial age was significant, indicating that observed age does not provide additional information after controlling for arterial age. Framingham risk calculated using this arterial age was more predictive of short-term incident coronary events than Framingham risk on the basis of observed age (area under the receiver-operating characteristic curve 0.75 for Framingham risk on the basis of observed age and 0.79 using arterial age, p = 0.006). In conclusion, arterial age provides a convenient transformation of CAC from Agatston units to a scale more easily appreciated by patients and treating physicians.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Cardiovascular calcification outside of the coronary tree, known as extracoronary calcification (ECC), is highly prevalent, often occurs concurrently in multiple sites, and yet ...its prognostic value is unclear. Objective To determine whether multisite ECC is associated with coronary heart disease (CHD) events, CHD mortality, and all-cause mortality. Methods We evaluated 5903 participants from the Multi-Ethnic Study of Atherosclerosis without diabetes who underwent CT imaging for calcification of the aortic valve, aortic root, mitral valve, and thoracic aorta. Participants were followed for 10.3 years. Multivariable adjusted hazard ratios estimated risk of outcomes for increasing numbers of ECC sites (0, 1, 2, 3, and 4), and receiver operator characteristic analysis assessed model discrimination. Results Prevalence of any ECC was 45%; median age was 62 years. Compared with those without ECC, those with ECC in 4 sites had increased hazards of 4.5, 7.1 and 2.3 for CHD events, CHD mortality, and all-cause mortality, respectively, independent of traditional risk factors (TRF; all P ≤ .05), and had ≥2-fold increased hazards for outcomes independent of coronary artery calcification (CAC). Each additional site of ECC was positively associated with each outcome in a graded fashion. When added to TRF, ECC significantly increased the area under the receiver operator characteristic curve for all outcomes and modestly increased the area under the curve for mortality beyond TRF + CAC (0.799 to 0.802; P = .03). Conclusion Increasing multisite ECC has a graded association with higher CHD and mortality risk, contributing information beyond TRF. Multisite ECC incidentally identified on imaging can be used to improve individualized risk prediction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Although a coronary artery calcium (CAC) score of 0 is associated with a very low 10-year risk for cardiac events, this risk is nonzero. Subjects with a family history of coronary heart disease (CHD) ...has been associated with more subclinical atherosclerosis than subjects without a family history of CHD. The purpose of this study was to assess the significance of a family history for CHD in subjects with a CAC score of 0. The Multi-Ethnic Study of Atherosclerosis cohort includes 6,814 participants free of clinical cardiovascular disease (CVD) at baseline. Positive family history was defined as reporting a parent, sibling, or child who had a heart attack. Time to incident CHD or CVD event was modeled using the multivariable Cox regression; 3,185 subjects were identified from the original Multi-Ethnic Study of Atherosclerosis cohort as having a baseline CAC score of 0 (mean age 58 years, 37% men). Over a median follow-up of 10 years, 101 participants (3.2%) had CVD events and 56 (1.8%) had CHD events. In age- and gender-adjusted analyses, a family history of CHD was associated with an ∼70% increase in CVD (hazard ratio 1.73, 95% confidence interval 1.17 to 2.56) and CHD (hazard ratio 1.72, 95% confidence interval 1.01 to 2.91) events. CVD events remained significant after further adjustment for ethnicity, risk factors, and baseline medication use. In conclusion, asymptomatic subjects with a 0 CAC score and a positive family history of CHD are at increased risk for CVD and CHD events compared with those without a family history of CHD, although absolute event rates remain low.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Systemic inflammation has been linked to the development of heart failure in population studies including Multi-Ethnic Study of Atherosclerosis (MESA), but little evidence exists regarding ...potential mechanism of this relationship. In this study, we used longitudinal magnetic resonance imaging follow-up analysis to examine whether C-reactive protein (CRP) levels relate to progressive myocardial functional deterioration as a potential mechanism of incident heart failure. Methods Regional myocardial functional data from MESA participants who had baseline CRP measurement and also underwent tagged cardiac magnetic resonance imaging both at baseline and at 5-year follow-up were analyzed. Left ventricular midwall and midslice peak circumferential strain (Ecc), of which a more negative value denotes stronger regional myocardial function, was measured. Circumferential strain change was calculated as the difference between baseline and follow-up Ecc. Results During the follow-up period, participants (n = 785) with elevated CRP experienced a decrease in strain, independent of age, gender, and ethnicity ( B = 0.081, ∆Ecc change per 1 mg/L CRP change, 95% CI 0.036-0.126, P < .001, model 1) and, additionally, beyond systolic blood pressure, heart rate, diabetes, smoking status, body mass index, current medication, and glomerular filtration rate ( B = 0.099, 0.052-0.145, P < .001, model 2). The relationship remained statistically significant after further adjustment for left ventricular mass, coronary calcium score, and interim clinical coronary events ( B = 0.098, 0.049-0.147, P < .001, model 3). Conclusion Higher CRP levels are related to progressive myocardial functional deterioration independent of subclinical atherosclerosis and clinical coronary events in asymptomatic individuals without previous history of heart disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Depression, chronic stress, and low levels of social support have known associations with cardiovascular disease (CVD). Physical activity has been shown to promote psychological health, reduce the ...frequency of depressive symptoms, and is associated with fewer cardiovascular events in depressed subjects with known CVD. The purpose of the present study was to test the hypothesis that physical activity attenuates the association between psychosocial factors and incident CVD. The Multi-Ethnic Study of Atherosclerosis cohort includes 6,814 participants free of clinical CVD at baseline. Complete data on physical activity were available for 6,795 subjects (mean age 62 years; 47% men). Psychosocial factors were assessed using standardized questionnaires. Cox proportional hazard models were used to evaluate the association between psychosocial factors and CVD events and its modulation by physical activity. In models adjusted for age, gender, and race/ethnicity, both depression and chronic burden were associated with CVD events (hazard ratio HR = 1.38 1.04 to 1.84, p = 0.028 for depression; HR = 1.15 1.05 to 1.24, p = 0.001 for chronic burden). Adjusting for physical activity, the relation between depression, chronic burden, and CVD events was not significantly reduced (HR = 1.35 1.02 to 1.80, p = 0.039 for depression; HR = 1.14 1.05 to 1.23, p = 0.001 for chronic burden). Although physical activity is an important component of physical and psychological health and well-being, it did not significantly attenuate the strong relation between depression or chronic burden and incident CVD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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