Abstract
Aims
While coronary artery calcium (CAC) has been extensively validated for predicting clinical events, most outcome studies of CAC have evaluated coronary heart disease (CHD) rather than ...atherosclerotic cardiovascular disease (ASCVD) events (including stroke). Also, virtually all CAC studies are of short- or intermediate-term follow-up, so studies across multi-ethnic cohorts with long-term follow-up are warranted prior to widespread clinical use. We sought to evaluate the contribution of CAC using the population-based MESA cohort with over 10 years of follow-up for ASCVD events, and whether the association of CAC with events varied by sex, race/ethnicity, or age category.
Methods and results
We utilized MESA, a prospective multi-ethnic cohort study of 6814 participants (51% women), aged 45–84 years, free of clinical CVD at baseline. We evaluated the relationship between CAC and incident ASCVD using Cox regression models adjusted for age, race/ethnicity, sex, education, income, cigarette smoking status, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes, lipid-lowering medication, systolic blood pressure, antihypertensive medication, intentional physical exercise, and body mass index. Only the first event for each individual was used in the analysis. Overall, 500 incident ASCVD (7.4%) events were observed in the total study population over a median of 11.1 years. Hard ASCVD included 217 myocardial infarction, 188 strokes (not transient ischaemic attack), 13 resuscitated cardiac arrest, and 82 CHD deaths. Event rates in those with CAC = 0 Agatston units ranged from 1.3% to 5.6%, while for those with CAC > 300, the 10-year event rates ranged from 13.1% to 25.6% across different age, gender, and racial subgroups. At 10 years of follow-up, all participants with CAC > 100 were estimated to have >7.5% risk regardless of demographic subset. Ten-year ASCVD event rates increased steadily across CAC categories regardless of age, sex, or race/ethnicity. For each doubling of CAC, we estimated a 14% relative increment in ASCVD risk, holding all other risk factors constant. This association was not significantly modified by age, sex, race/ethnicity, or baseline lipid-lowering use.
Conclusions
Coronary artery calcium is associated strongly and in a graded fashion with 10-year risk of incident ASCVD as it is for CHD, independent of standard risk factors, and similarly by age, gender, and ethnicity. While 10-year event rates in those with CAC = 0 were almost exclusively below 5%, those with CAC ≥ 100 were consistently above 7.5%, making these potentially valuable cutpoints for the consideration of preventive therapies. Coronary artery calcium strongly predicts risk with the same magnitude of effect in all races, age groups, and both sexes, which makes it among the most useful markers for predicting ASCVD risk.
Background: Recent epidemiologic studies have found that self-reported duration of sleep is associated with obesity, diabetes, hypertension, and mortality. The extent to which self reports of sleep ...duration are similar to objective measures and whether individual characteristics influence the degree of similarity are not known. Methods: Eligible participants at the Chicago site of the Coronary Artery Risk Development in Young Adults Study were invited to participate in a 2003–2005 ancillary sleep study; 82% (n = 669) agreed. Sleep measurements collected in 2 waves included 3 days each of wrist actigraphy, a sleep log, and questions about usual sleep duration. We estimate the average difference and correlation between subjectively and objectively measured sleep by using errors-in-variables regression models. Results: Average measured sleep was 6 hours, whereas the average from subjective reports was 6.8 hours. Subjective reports increased on average by 34 minutes for each additional hour of measured sleep. Overall, the correlation between reported and measured sleep duration was 0.47. Our model suggests that persons sleeping 5 hours over-reported their sleep duration by 1.2 hours, and those sleeping 7 hours over-reported by 0.4 hours. The correlations and average differences between self-reports and measured sleep varied by health, sociodemographic, and sleep characteristics. Conclusion: In a population-based sample of middle-aged adults, subjective reports of habitual sleep are moderately correlated with actigraph-measured sleep, but are biased by systematic over-reporting. The true associations between sleep duration and health may differ from previously reported associations between self-reported sleep and health.
Objective The purpose of this study was to evaluate the relationship of left ventricular (LV) mass and geometry measured with cardiac magnetic resonance imaging (MRI) to incident cardiovascular ...events in the MESA (Multi-Ethnic Study of Atherosclerosis) study. Background MRI is highly accurate for evaluation of heart size and structure and has not previously been used in a large epidemiologic study to predict cardiovascular events. Methods A total of 5,098 participants in the MESA study underwent cardiac MRI at the baseline examination and were followed up for a median of 4 years. Cox proportional hazard models were constructed to predict the end points of coronary heart disease (CHD), stroke, and heart failure (HF) after adjustment for cardiovascular risk factors. Results A total of 216 incident events were observed during the follow-up period. In adjusted models, the end points of incident CHD and stroke were positively associated with increased LV mass-to-volume ratio (CHD, hazard ratio HR: 2.1 per g/ml, p = 0.02; stroke, HR: 4.2 per g/ml, p = 0.005). In contrast, LV mass showed the strongest association with incident HF events (HR: 1.4 per 10% increment, p < 0.0001). The HF events occurred primarily in participants with LV hypertrophy, that is, ≥95th percentile of LV mass (HR: 8.6, 95% confidence interval: 3.7 to 19.9, reference group <50th percentile of LV mass). Conclusions The LV size was related to incident HF, stroke, and CHD in this multiethnic cohort. Whereas body size-adjusted LV mass alone predicted incident HF, concentric ventricular remodeling predicted incident stroke and CHD.
We compared South Asians with four other racial/ethnic groups in the U.S. to determine whether sociodemographic, lifestyle, or metabolic factors could explain the higher diabetes prevalence and ...whether insulin resistance and β-cell dysfunction occurred at younger ages and/or lower adiposity levels compared with other groups.
We performed a cross-sectional analysis of two community-based cohorts, the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study and the Multi-Ethnic Study of Atherosclerosis (MESA); all participants had no known cardiovascular disease and were between 44 and 84 years of age. We compared 799 South Asians with 2,611 whites, 1,879 African Americans, 1,493 Latinos, and 801 Chinese Americans. Type 2 diabetes was classified by fasting plasma glucose ≥126 mg/dL or use of a diabetes medication. Insulin resistance was estimated by the homeostasis model assessment (HOMA) and β-cell function was measured by the HOMA-β model.
South Asians had significantly higher age-adjusted prevalence of diabetes (23%) than the MESA ethnic groups (6% in whites, 18% in African Americans, 17% in Latinos, and 13% in Chinese Americans). This difference increased further after adjustment for potential confounders. HOMA of insulin resistance (HOMA-IR) levels were significantly higher and HOMA-β levels were lower among South Asians compared with all other racial/ethnic groups after adjustment for age and adiposity.
The higher prevalence of diabetes in South Asians is not explained by traditionally measured risk factors. South Asians may have lower β-cell function and an inability to compensate adequately for higher glucose levels from insulin resistance.
Purpose The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a multicenter, community-based cohort study of Hispanic/Latino adults in the United States. A diverse participant sample ...is required that is both representative of the target population and likely to remain engaged throughout follow-up. The choice of sample design, its rationale, and benefits and challenges of design decisions are described in this study. Methods The study design calls for recruitment and follow-up of a cohort of 16,000 Hispanics/Latinos 18–74 years of age, with 62.5% (10,000) over 44 years of age and adequate subgroup sample sizes to support inference by Hispanic/Latino background. Participants are recruited in community areas surrounding four field centers in the Bronx, Chicago, Miami, and San Diego. A two-stage area probability sample of households is selected with stratification and oversampling incorporated at each stage to provide a broadly diverse sample, offer efficiencies in field operations, and ensure that the target age distribution is obtained. Conclusions Embedding probability sampling within this traditional, multisite cohort study design enables competing research objectives to be met. However, the use of probability sampling requires developing solutions to some unique challenges in both sample selection and recruitment, as described here.
The results of cohort studies relating sodium (Na) intake to blood pressure-related cardiovascular disease (CVD) are inconsistent. To understand whether methodological issues account for the ...inconsistency, we reviewed the quality of these studies.
We reviewed cohort studies that examined the association between Na and CVD. We then identified methodological issues with greatest potential to alter the direction of association (reverse causality, systematic error in Na assessment), some potential to alter the direction of association (residual confounding, inadequate follow-up), and the potential to yield false null results (random error in Na assessment, insufficient power). We included 26 studies with 31 independent analyses. Of these, 13 found direct associations between Na and CVD, 8 found inverse associations, 2 found J-shaped associations, and 8 found null associations only. On average there were 3 to 4 methodological issues per study. Issues with greater potential to alter the direction of association were present in all but 1 of the 26 studies (systematic error, 22; reverse causality, 16). Issues with lesser potential to alter the direction of association were present in 18 studies, whereas those with potential to yield false null results were present in 23.
Methodological issues may account for the inconsistent findings in currently available observational studies relating Na to CVD. Until well-designed cohort studies in the general population are available, it remains appropriate to base Na guidelines on the robust body of evidence linking Na with elevated blood pressure and the few existing general population trials of the effects of Na reduction on CVD.
Coronary artery calcification is a subclinical predictor of coronary heart disease. Recent studies have found that sleep duration is correlated with established risk factors for calcification ...including glucose regulation, blood pressure, sex, age, education, and body mass index.
To determine whether objective and subjective measures of sleep duration and quality are associated with incidence of calcification over 5 years and whether calcification risk factors mediate the association.
Observational cohort of home monitoring in a healthy middle-aged population of 495 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort Chicago site (black and white men and women aged 35-47 years at year 15 of the study in 2000-2001 with follow-up data at year 20 in 2005-2006). Potential confounders (age, sex, race, education, apnea risk, smoking status) and mediators (lipids, blood pressure, body mass index, diabetes, inflammatory markers, alcohol consumption, depression, hostility, self-reported medical conditions) were measured at both baseline and follow-up. Sleep metrics (wrist actigraphy measured duration and fragmentation, daytime sleepiness, overall quality, self-reported duration) were examined for association with incident calcification. Participants had no detectable calcification at baseline.
Coronary artery calcification was measured by computed tomography in 2000-2001 and 2005-2006 and incidence of new calcification over that time was the primary outcome.
Five-year calcification incidence was 12.3% (n = 61). Longer measured sleep duration was significantly associated with reduced calcification incidence (adjusted odds ratio, 0.67 per hour 95% confidence interval, 0.49-0.91 per hour; P = .01). No potential mediators appreciably altered the magnitude or significance of sleep (adjusted odds ratio estimates ranged from 0.64 to 0.68 per sleep hour; maximum P = .02). Alternative sleep metrics were not significantly associated with calcification.
Longer measured sleep is associated with lower calcification incidence independent of examined potential mediators and confounders.
Clinical practice guidelines state there is insufficient evidence to support advising patients with peripheral artery disease (PAD) to participate in a home-based walking exercise program.
To ...determine whether a home-based walking exercise program that uses a group-mediated cognitive behavioral intervention, incorporating both group support and self-regulatory skills, can improve functional performance compared with a health education control group in patients with PAD with and without intermittent claudication.
Randomized controlled clinical trial of 194 patients with PAD, including 72.2% without classic symptoms of intermittent claudication, performed in Chicago, Illinois between July 22, 2008, and December 14, 2012.
Participants were randomized to 1 of 2 parallel groups: a home-based group-mediated cognitive behavioral walking intervention or an attention control condition.
The primary outcome was 6-month change in 6-minute walk performance. Secondary outcomes included 6-month change in treadmill walking, physical activity, the Walking Impairment Questionnaire (WIQ), and Physical and Mental Health Composite Scores from the 12-item Short-Form Health Survey.
Participants randomized to the intervention group significantly increased their 6-minute walk distance (reported in meters 357.4 to 399.8 vs 353.3 to 342.2 for those in the control group; mean difference, 53.5 95% CI, 33.2 to 73.8; P < .001), maximal treadmill walking time (intervention, 7.91 to 9.44 minutes vs control, 7.56 to 8.09; mean difference, 1.01 minutes 95% CI, 0.07 to 1.95; P = .04), accelerometer-measured physical activity over 7 days (intervention, 778.0 to 866.1 vs control, 671.6 to 645.0; mean difference, 114.7 activity units 95% CI, 12.82 to 216.5; P = .03), WIQ distance score (intervention, 35.3 to 47.4 vs control, 33.3 to 34.4; mean difference, 11.1 95% CI, 3.9 to 18.1; P = .003), and WIQ speed score (intervention, 36.1 to 47.7 vs control, 35.3-36.6; mean difference, 10.4 95% CI, 3.4 to 17.4; P = .004).
A home-based walking exercise program significantly improved walking endurance, physical activity, and patient-perceived walking endurance and speed in PAD participants with and without classic claudication symptoms. These findings have implications for the large number of patients with PAD who are unable or unwilling to participate in supervised exercise programs.
clinicaltrials.gov Identifier: NCT00693940.
Single measures of blood pressure (BP) levels are associated with the development of atherosclerosis; however, long-term patterns in BP and their effect on cardiovascular disease risk are poorly ...characterized.
To identify common BP trajectories throughout early adulthood and to determine their association with presence of coronary artery calcification (CAC) during middle age.
Prospective cohort data from 4681 participants in the CARDIA study, who were black and white men and women aged 18 to 30 years at baseline in 1985-1986 at 4 urban US sites, collected through 25 years of follow-up (2010-2011). We examined systolic BP, diastolic BP, and mid-BP (calculated as SBP+DBP/2, an important marker of coronary heart disease risk among younger populations) at baseline and years 2, 5, 7, 10, 15, 20, and 25. Latent mixture modeling was used to identify trajectories in systolic, diastolic, and mid-BP over time.
Coronary artery calcification greater than or equal to Agatston score of 100 Hounsfield units (HU) at year 25.
We identified 5 distinct mid-BP trajectories: low-stable (21.8%; 95% CI, 19.9%-23.7%; n=987), moderate-stable (42.3%; 40.3%-44.3%; n=2085), moderate-increasing (12.2%; 10.4%-14.0%; n=489), elevated-stable (19.0%; 17.1%-20.0%; n=903), and elevated-increasing (4.8%; 4.0%-5.5%; n=217). Compared with the low-stable group, trajectories with elevated BP levels had greater odds of having a CAC score of 100 HU or greater. Adjusted odds ratios were 1.44 (95% CI, 0.83-2.49) for moderate-stable, 1.86 (95% CI, 0.91-3.82) for moderate-increasing, 2.28 (95% CI, 1.24-4.18), for elevated-stable, and 3.70 (95% CI, 1.66-8.20) for elevated-increasing groups. The adjusted prevalence of a CAC score of 100 HU or higher was 5.8% in the low-stable group. These odds ratios represent an absolute increase of 2.7%, 5%, 6.3%, and 12.9% for the prevalence of a CAC score of 100 HU or higher for the moderate-stable, moderate-increasing, elevated-stable and elevated-increasing groups, respectively, compared with the low-stable group. Associations were not altered after adjustment for baseline and year 25 BP. Findings were similar for trajectories of isolated systolic BP trajectories but were attenuated for diastolic BP trajectories.
Blood pressure trajectories throughout young adulthood vary, and higher BP trajectories were associated with an increased risk of CAC in middle age. Long-term trajectories in BP may assist in more accurate identification of individuals with subclinical atherosclerosis.
The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events.
CAC predicts CHD events and serial measurement of CAC has been ...proposed to evaluate atherosclerosis progression.
We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors.
A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression.
Progression of CAC is associated with an increased risk for future hard and total CHD events.
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