Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial.

Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans (AAs). Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2571 AAs from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary, or carotid artery revascularization) and CKD (eGFR under 60 ml/min per 1.73 m(2) and/or UACR over 30 mg/g). AA SPRINT participants were 45.3% female with a mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mm Hg, eGFR 76.3 (77.1) ml/min per 1.73 m(2), and UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08-1.73) and log UACR estimated slope (ß) 0.33) and negatively associated with eGFR (ß -3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82-1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not with prevalent CVD in AAs with a UACR under 1000 mg/g.

Prevalence and Correlates of Myocardial Scar in a US Cohort.

IMPORTANCE: Myocardial scarring leads to cardiac dysfunction and poor prognosis. The prevalence of and factors associated with unrecognized myocardial infarction and scar have not been previously defined using contemporary methods in a multiethnic US population. OBJECTIVE: To determine prevalence of and factors associated with myocardial scar in middle- and older-aged individuals in the United States. DESIGN, SETTING, AND PARTICIPANTS: The Multi-Ethnic Study of Atherosclerosis (MESA) study is a population-based cohort in the United States. Participants were aged 45 through 84 years and free of clinical cardiovascular disease (CVD) at baseline in 2000-2002. In the 10th year examination (2010-2012), 1840 participants underwent cardiac magnetic resonance (CMR) imaging with gadolinium to detect myocardial scar. Cardiovascular disease risk factors and coronary artery calcium (CAC) scores were measured at baseline and year 10. Logistic regression models were used to estimate adjusted odds ratios (ORs) for myocardial scar. EXPOSURES: Cardiovascular risk factors, CAC scores, left ventricle size and function, and carotid intima-media thickness. MAIN OUTCOMES AND MEASURES: Myocardial scar detected by CMR imaging. RESULTS: Of 1840 participants (mean [SD] age, 68 [9] years, 52% men), 146 (7.9%) had myocardial scars, of which 114 (78%) were undetected by electrocardiogram or by clinical adjudication. In adjusted models, age, male sex, body mass index, hypertension, and current smoking at baseline were associated with myocardial scar at year 10. The OR per 8.9-year increment was 1.61 (95% CI, 1.36-1.91; P < .001); for men vs women: OR, 5.76 (95% CI, 3.61-9.17; P < .001); per 4.8-SD body mass index: OR, 1.32 (95% CI, 1.09-1.61, P = .005); for hypertension: OR, 1.61 (95% CI, 1.12-2.30; P = .009); and for current vs never smokers: 2.00 (95% CI, 1.22-3.28; P = .006). Age-, sex-, and ethnicity-adjusted CAC scores at baseline were also associated with myocardial scar at year 10. Compared with a CAC score of 0, the OR for scores from 1 through 99 was 2.4 (95% CI, 1.5-3.9); from 100 through 399, 3.0 (95% CI, 1.7-5.1), and 400 or higher, 3.3 (95% CI, 1.7-6.1) (P ≤ .001). The CAC score significantly added to the association of myocardial scar with age, sex, race/ethnicity, and traditional CVD risk factors (C statistic, 0.81 with CAC vs 0.79 without CAC, P = .01). CONCLUSIONS AND RELEVANCE: The prevalence of myocardial scars in a US community-based multiethnic cohort was 7.9%, of which 78% were unrecognized by electrocardiography or clinical evaluation. Further studies are needed to understand the clinical consequences of these undetected scars.

The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men.

Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation. Potential limitations Setting the serum testosterone concentration sufficiently low to ensure that most men would be unequivocally testosterone deficient, as well as many other entry criteria, resulted in screening approximately 30 men in person to randomize one participant. Conclusion Designing The Testosterone Trials as a coordinated set of seven trials afforded many important scientific and logistical advantages but required an intensive recruitment and screening effort.

Cardiovascular epidemiology in a changing world--challenges to investigators and the National Heart, Lung, and Blood Institute.

Over the past 60 years, revolutionary discoveries made by epidemiologists have contributed to marked declines in cardiovascular disease morbidity and mortality. Now, in an era of increasingly constrained resources, researchers in cardiovascular epidemiology face a number of challenges that call for novel, paradigm-shifting approaches. In this paper, the authors pose to the community 4 critical questions: 1) How can we avoid wasting resources on studies that provide little incremental knowledge? 2) How can we assure that we direct our resources as economically as possible towards innovative science? 3) How can we be nimble, responding quickly to new opportunities? 4) How can we identify prospectively the most meritorious research questions? Senior program staff at the National Heart, Lung, and Blood Institute invite the epidemiology community to join them in an ongoing Web-based blog conversation so that together we might develop novel approaches that will facilitate the next generation of high-impact discoveries.

Coronary calcium as a predictor of coronary events in four racial or ethnic groups.

BACKGROUND: In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. METHODS: We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years. RESULTS: There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. CONCLUSIONS: The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected.

Prevention of atrial fibrillation: report from a national heart, lung, and blood institute workshop.

The National Heart, Lung, and Blood Institute convened an expert panel April 28 to 29, 2008, to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed the existing basic scientific, epidemiological, and clinical literature about AF and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: (1) enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; (2) improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; (3) improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural, and electrical remodeling markers; (4) develop additional animal models reflective of the pathophysiology of human AF; (5) conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and (6) conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations.

Coronary artery calcium score and risk classification for coronary heart disease prediction.

CONTEXT: The coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear. OBJECTIVE: To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk. DESIGN, SETTING, AND PARTICIPANTS: CACS was measured by computed tomography in 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded from the primary analysis. Five-year risk estimates for incident CHD were categorized as 0% to less than 3%, 3% to less than 10%, and 10% or more using Cox proportional hazards models. Model 1 used age, sex, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement and compared the distribution of risk using model 2 vs model 1. MAIN OUTCOME MEASURES: Incident CHD events. RESULTS: During a median of 5.8 years of follow-up among a final cohort of 5878, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement = 0.25; 95% confidence interval, 0.16-0.34; P < .001). In model 1, 69% of the cohort was classified in the highest or lowest risk categories compared with 77% in model 2. An additional 23% of those who experienced events were reclassified as high risk, and an additional 13% without events were reclassified as low risk using model 2. CONCLUSION: In this multi-ethnic cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.

Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: The Multi-Ethnic Study of Atherosclerosis (MESA) provides an opportunity to study the association of traditional cardiovascular risk factors with the incidence and progression of coronary artery calcium (CAC) in a large community-based cohort with no evidence of clinical cardiovascular disease. METHODS AND RESULTS: Follow-up CAC measurements were available for 5756 participants with an average of 2.4 years between scans. The incidence of newly detectable CAC averaged 6.6% per year. Incidence increased steadily across age, ranging from <5% annually in those <50 years of age to >12% in those >80 years of age. Median annual change in CAC for those with existing calcification at baseline was 14 Agatston units for women and 21 Agatston units for men. Most traditional cardiovascular risk factors were associated with both the risk of developing new incident coronary calcium and increases in existing calcification. These included age, male gender, white race/ethnicity, hypertension, body mass index, diabetes mellitus, glucose, and family history of heart attack. Factors also existed that were related only to incident CAC risk, such as low- and high-density lipoprotein cholesterol and creatinine. Diabetes mellitus had the strongest association with CAC progression for blacks and the weakest for Hispanics, with intermediate associations for whites and Chinese. CONCLUSIONS: This is the first large multiethnic study reporting on the incidence and progression of CAC. Standard coronary risk factors were generally related to both CAC incidence and progression. Whites had more incident CAC and CAC progression than the other 3 racial/ethnic groups. Except for diabetes mellitus, risk factor relationships were similar across racial/ethnic groups.

Risk factor associations with the presence of a lipid core in carotid plaque of asymptomatic individuals using high-resolution MRI: the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND AND PURPOSE: Atheroma vulnerability to rupture is increased in the presence of a large lipid core. Factors associated with a lipid core in the general population have not been studied. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study of individuals free of clinical cardiovascular disease designed to include a high proportion of ethnic minorities. We selected MESA participants from the top 15th percentile of maximum carotid intima media thickness by ultrasound and acquired high-resolution black blood MRI images through their carotid plaque before and after the intravenous administration of gadodiamide (0.1 mmol/kg). Lumen and outer wall contours were defined using semiautomated analysis software. We analyzed only plaques with a maximum thickness >or=1.5 mm by MRI (n=214) and assessed cross-sectional risk factor associations with lipid core presence by multivariable logistic regression. RESULTS: A lipid core was present in 151 (71%) of the plaques. After controlling for age, ethnicity, sex, maximum arterial wall thickness, hypertension, cigarette smoking, diabetes, and C-reactive protein, compared with participants in the lowest tertile of total plasma cholesterol, the ORs of having a lipid core for participants in the middle and highest tertiles were 2.76 (95% CI: 1.01 to 7.51) and 4.63 (95% CI: 1.56 to 13.75), respectively. None of the other risk factors was associated with lipid core. CONCLUSIONS: In persons with thickened carotid walls, plasma total cholesterol, but not other established coronary heart disease risk factors, is strongly associated with lipid core presence by MRI. High total cholesterol may be associated with rupture proneness of atherosclerotic lesions in the general population.

Ethnic differences in coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: There is substantial evidence that coronary calcification, a marker for the presence and quantity of coronary atherosclerosis, is higher in US whites than blacks; however, there have been no large population-based studies comparing coronary calcification among US ethnic groups. METHODS AND RESULTS: Using computed tomography, we measured coronary calcification in 6814 white, black, Hispanic, and Chinese men and women aged 45 to 84 years with no clinical cardiovascular disease who participated in the Multi-Ethnic Study of Atherosclerosis (MESA). The prevalence of coronary calcification (Agatston score >0) in these 4 ethnic groups was 70.4%, 52.1%, 56.5%, and 59.2%, respectively, in men (P<0.001) and 44.6%, 36.5%, 34.9%, and 41.9%, respectively, (P<0.001) in women. After adjustment for age, education, lipids, body mass index, smoking, diabetes, hypertension, treatment for hypercholesterolemia, gender, and scanning center, compared with whites, the relative risks for having coronary calcification were 0.78 (95% CI 0.74 to 0.82) in blacks, 0.85 (95% CI 0.79 to 0.91) in Hispanics, and 0.92 (95% CI 0.85 to 0.99) in Chinese. After similar adjustments, the amount of coronary calcification among those with an Agatston score >0 was greatest among whites, followed by Chinese (77% that of whites; 95% CI 62% to 96%), Hispanics (74%; 95% CI 61% to 90%), and blacks (69%; 95% CI 59% to 80%). CONCLUSIONS: We observed ethnic differences in the presence and quantity of coronary calcification that were not explained by coronary risk factors. Identification of the mechanism underlying these differences would further our understanding of the pathophysiology of coronary calcification and its clinical significance. Data on the predictive value of coronary calcium in different ethnic groups are needed.

Legacy of MESA.

The MESA (Multi-Ethnic Study of Atherosclerosis) was initiated to address unresolved questions about subclinical cardiovascular disease and its progression to clinically overt cardiovascular disease in a diverse population-based sample, incorporating emerging imaging technologies for better evaluation of subclinical disease and creating a population laboratory for future research. MESA's recruited (from 2000 to 2002) cohort comprised >6,000 adults from 4 racial/ethnic groups, ages 45 to 84 years, who were free of cardiovascular disease at baseline. Extensive cohort data have been collected over 5 exams (through 2011) with additional exam components added through extramurally funded ancillary study grants, and through regular phone follow-up contacts. Over 1,000 MESA papers have been published to date. Exam 6 will incorporate components that use novel wearable, imaging, and other technologies to address new research questions. MESA investigators have and continue to seek opportunities for collaboration with other researchers on a wide variety of topics to further expand the science of MESA.

Calcium Intake From Diet and Supplements and the Risk of Coronary Artery Calcification and its Progression Among Older Adults: 10-Year Follow-up of the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Recent randomized data suggest that calcium supplements may be associated with increased risk of cardiovascular disease (CVD) events. Using a longitudinal cohort study, we assessed the association between calcium intake, from both foods and supplements, and atherosclerosis, as measured by coronary artery calcification (CAC). METHODS AND RESULTS: We studied 5448 adults free of clinically diagnosed CVD (52% female; aged 45-84 years) from the Multi-Ethnic Study of Atherosclerosis. Baseline total calcium intake was assessed from diet (using a food frequency questionnaire) and calcium supplements (by a medication inventory) and categorized into quintiles. Baseline CAC was measured by computed tomography, and CAC measurements were repeated in 2742 participants ≈10 years later. At baseline, mean calcium intakes across quintiles were 313.3, 540.3, 783.0, 1168.9, and 2157.4 mg/day. Women had higher calcium intakes than men. After adjustment for potential confounders, among 1567 participants without baseline CAC, the relative risk (RR) of developing incident CAC over 10 years, by quintile 1 to 5 of calcium intake, were 1 (reference), 0.95 (0.79-1.14), 1.02 (0.85-1.23), 0.86 (0.69-1.05), and 0.73 (0.57-0.93). After accounting for total calcium intake, calcium supplement use was associated with increased risk for incident CAC (RR=1.22 [1.07-1.39]). No relation was found between baseline calcium intake and 10-year changes in log-transformed CAC among those participants with baseline CAC >0. CONCLUSIONS: High total calcium intake was associated with a decreased risk of incident atherosclerosis over long-term follow-up, particularly if achieved without supplement use. However, calcium supplement use may increase the risk for incident CAC.

Demographics and correlates of five-year change in echocardiographic left ventricular mass in young black and white adult men and women: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

OBJECTIVE: The goal of this study was to determine the presence and correlates of change (Delta) in left ventricular (LV) mass by echocardiography in young adults. BACKGROUND: Left ventricular mass is known to be a powerful independent predictor for cardiovascular disease events in adults. However, little is known about Delta in LV mass over time in young adults. METHODS: Coronary Artery Risk Development in Young Adults (CARDIA) is a multicenter, longitudinal, population-based study of black and white men and women who were ages 23 to 35 at the time of their initial two-dimensionally directed M-mode echocardiography exam (year 5); half the cohort had a repeat echocardiography exam five years later (year 10). Data were analyzed from 1,189 participants who had paired echocardiography studies. To minimize reader variability, blinded measurements on initial and repeat echocardiography were performed nearly contemporaneously by the same reader. RESULTS: In multilinear regression analyses, significant (p < 0.05) predictors of year 10 two-dimensional guided M-mode LV mass included initial LV mass, initial body mass index (BMI) and change in BMI for all race/gender subgroups. Initial systolic blood pressure (SBP) was a significant predictor of year 10 LV mass in white men and black women; change in SBP was significant in black women with a trend towards significance in white women. Left ventricular mass remained constant in all race/gender subgroups, except black women, where it increased (by 5.9 g [mean]). Black women also had the largest increases in BMI and SBP. In black women, a five-year weight gain of 20 pounds and a 15-mm Hg increase in SBP would be expected to be associated with a 9% to 12% increase in LV mass. CONCLUSIONS: Particularly in black women, weight and blood pressure control may be important community health and treatment goals to prevent LV hypertrophy.

10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study).

BACKGROUND: Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to date, no risk score incorporating CAC has been developed. OBJECTIVES: The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors. METHODS: Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study). RESULTS: Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p < 0.0001). External validation in both the HNR and DHS studies provided evidence of very good discrimination and calibration. Harrell's C-statistic was 0.779 in HNR and 0.816 in DHS. Additionally, the difference in estimated 10-year risk between events and nonevents was approximately 8% to 9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within one-half of a percent of the observed event rate. CONCLUSIONS: An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies.

Positional change in blood pressure and 8-year risk of hypertension: the CARDIA Study.

OBJECTIVE: To assess the relationship between positional blood pressure change and 8-year incidence of hypertension in a biracial cohort of young adults. SUBJECTS AND METHODS: Participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study with complete data from year 2 (1987-1988), year 5 (1990-1991), year 7 (1992-1993), and year 10 (1995-1996) examinations were included (N = 2781). Participants were classified into 3 groups based on their year 2 systolic blood pressure response to standing: drop, a decrease in systolic blood pressure of more than 5 mm Hg; same, a change of between -5 and +5 mm Hg; and rise, more than 5-mm Hg increase. RESULTS: The number of participants in each group was as follows: drop, 741; same, 1590; and rise, 450. The 8-year incidence of hypertension was 8.4% in the drop group, 6.8% in the same group, and 12.4% in the rise group (P < .001). Adjusted odds ratios for developing hypertension during the follow-up period in the rise group vs the same group were as follows: in black men, 2.85 (95% confidence interval [CI], 1.43-5.69), in black women, 2.47 (95% CI, 1.19-5.11), in white men, 2.17 (95% CI, 1.00-4.73), and in white women, 4.74 (95% CI, 1.11-20.30). CONCLUSIONS: A greater than 5-mm Hg increase in blood pressure on standing identified a group of young adults at increased risk of developing hypertension within 8 years. These findings support a physiologic link between sympathetic nervous system reactivity and risk of hypertension in young adults.

Ten-year trends in coronary calcification in individuals without clinical cardiovascular disease in the multi-ethnic study of atherosclerosis.

BACKGROUND: Coronary heart disease (CHD) incidence has declined significantly in the US, as have levels of major coronary risk factors, including LDL-cholesterol, hypertension and smoking, but whether trends in subclinical atherosclerosis mirror these trends is not known. METHODS AND FINDINGS: To describe recent secular trends in subclinical atherosclerosis as measured by serial evaluations of coronary artery calcification (CAC) prevalence in a population over 10 years, we measured CAC using computed tomography (CT) and CHD risk factors in five serial cross-sectional samples of men and women from four race/ethnic groups, aged 55-84 and without clinical cardiovascular disease, who were members of Multi-Ethnic Study of Atherosclerosis (MESA) cohort from 2000 to 2012. Sample sizes ranged from 1062 to 4837. After adjusting for age, gender, and CT scanner, the prevalence of CAC increased across exams among African Americans, whose prevalence of CAC was 52.4% in 2000-02, 50.4% in 2003-04, 60.0% is 2005-06, 57.4% in 2007-08, and 61.3% in 2010-12 (p for trend <0.001). The trend was strongest among African Americans aged 55-64 [prevalence ratio for 2010-12 vs. 2000-02, 1.59 (95% confidence interval 1.06, 2.39); p = 0.005 for trend across exams]. There were no consistent trends in any other ethnic group. Risk factors generally improved in the cohort, and adjustment for risk factors did not change trends in CAC prevalence. CONCLUSIONS: There was a significant secular trend towards increased prevalence of CAC over 10 years among African Americans and no change in three other ethnic groups. Trends did not reflect concurrent general improvement in risk factors. The trend towards a higher prevalence of CAC in African Americans suggests that CHD risk in this population is not improving relative to other groups.

Progression of coronary calcium and incident coronary heart disease events: MESA (Multi-Ethnic Study of Atherosclerosis).

OBJECTIVES: The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events. BACKGROUND: CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. METHODS: 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. RESULTS: 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. CONCLUSIONS: Progression of CAC is associated with an increased risk for future hard and total CHD events.

Distribution of coronary artery calcium scores by Framingham 10-year risk strata in the MESA (Multi-Ethnic Study of Atherosclerosis) potential implications for coronary risk assessment.

OBJECTIVES: By examining the distribution of coronary artery calcium (CAC) levels across Framingham risk score (FRS) strata in a large, multiethnic, community-based sample of men and women, we sought to determine if lower-risk persons could benefit from CAC screening. BACKGROUND: The 10-year FRS and CAC levels are predictors of coronary heart disease. A CAC level of 300 or more is associated with the highest risk for coronary heart disease even in low-risk persons (FRS, <10%); however, expert groups have suggested CAC screening only in intermediate-risk groups (FRS, 10% to 20%). METHODS: We included 5,660 Multi-Ethnic Study of Atherosclerosis participants. The number needed to screen (number of people that need to be screened to detect 1 person with CAC level above the specified cutoff point) was used to assess the yield of screening for CAC. CAC prevalence was compared across FRS strata using chi-square tests. RESULTS: CAC levels of more than 0, of 100 or more, and of 300 or more were present in 46.4%, 20.6%, and 10.1% of participants, respectively. The prevalence and amount of CAC increased with higher FRS. A CAC level of 300 or more was observed in 1.7% and 4.4% of those with FRS of 0% to 2.5% and of 2.6% to 5%, respectively (number needed to screen, 59.7 and 22.7, respectively). Likewise, a CAC level of 300 or more was observed in 24% and 30% of those with FRS of 15.1% to 20% and more than 20%, respectively (number needed to screen, 4.2 and 3.3, respectively). Trends were similar when stratified by age, sex, and race or ethnicity. CONCLUSIONS: Our study suggests that in very low-risk individuals (FRS ≤5%), the yield of screening and probability of identifying persons with clinically significant levels of CAC is low, but becomes greater in low- and intermediate-risk persons (FRS 5.1% to 20%).

Cardiovascular imaging for assessing cardiovascular risk in asymptomatic men versus women: the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: Coronary artery calcium (CAC), carotid intima-media thickness, and left ventricular (LV) mass and geometry offer the potential to characterize incident cardiovascular disease (CVD) risk in clinically asymptomatic individuals. The objective of the study was to compare these cardiovascular imaging measures for their overall and sex-specific ability to predict CVD. METHODS AND RESULTS: The study sample consisted of 4965 Multi-Ethnic Study of Atherosclerosis participants (48% men; mean age, 62±10 years). They were free of CVD at baseline and were followed for a median of 5.8 years. There were 297 CVD events, including 187 coronary heart disease (CHD) events, 65 strokes, and 91 heart failure (HF) events. CAC was most strongly associated with CHD (hazard ratio [HR], 2.3 per 1 SD; 95% CI, 1.9 to 2.8) and all CVD events (HR, 1.7; 95% CI, 1.5 to 1.9). Most strongly associated with stroke were LV mass (HR, 1.3; 95% CI, 1.1 to 1.7) and LV mass/volume ratio (HR, 1.3; 95% CI, 1.1 to 1.6). LV mass showed the strongest association with HF (HR, 1.8; 95% CI, 1.6 to 2.1). There were no significant interactions for imaging measures with sex and ethnicity for any CVD outcome. Compared with traditional risk factors alone, overall risk prediction (C statistic) for future CHD, HF, and all CVD was significantly improved by adding CAC, LV mass, and CAC, respectively (all P<0.05). CONCLUSIONS: There was no evidence that imaging measures differed in association with incident CVD by sex. CAC was most strongly associated with CHD and CVD; LV mass and LV concentric remodeling best predicted stroke; and LV mass best predicted HF.