The purpose of this study was to assess the prevalence and distribution of coronary artery calcium (CAC) across Framingham Risk Score (FRS) strata and therefore determine FRS levels at which asymptomatic, young to early middle-age individuals could potentially benefit from CAC screening.
High CAC burden is associated with increased risk of coronary events beyond the FRS. Expert panel recommendations for CAC screening are based on data obtained in middle-age and older individuals.
We included 2,831 CARDIA (Coronary Artery Risk Development in Young Adults) study participants with an age range of 33 to 45 years. The number needed to screen ([NNS] number of people in each FRS stratum who need to be screened to detect 1 person with a CAC score above the specified cut point) was used to assess the yield of screening for CAC. CAC prevalence was compared across FRS strata using a chi-square test.
CAC scores >0 and ≥100 were present in 9.9% and 1.8% of participants, respectively. CAC prevalence and amount increased across higher FRS strata. A CAC score >0 was observed in 7.3%, 20.2%, 19.1%, and 44.8% of individuals with FRSs of 0 to 2.5%, 2.6% to 5%, 5.1% to 10%, and >10%, respectively (NNS = 14, 5, 5, and 2, respectively). A CAC score of ≥100 was observed in 1.3%, 2.4%, and 3.5% of those with FRSs of 0 to 2.5%, 2.6% to 5%, and 5.1% to 10%, respectively (NNS = 79, 41, and 29, respectively), but in 17.2% of those with an FRS >10% (NNS = 6). Similar trends were observed when findings were stratified by sex and race.
In this young to early middle-age cohort, we observed concordance between CAC prevalence/amount and FRS strata. Within this group, the yield of screening and possibility of identifying those with a high CAC burden (CAC score of ≥100) is low in those with an FRS of ≤10%, but considerable in those with an FRS >10%.
coronary artery calcium; coronary heart disease; Framingham Risk Score; number needed to screen; risk factors
Individuals with electrocardiographically-determined left ventricular hypertrophy (ECG LVH) are at risk for multiple cardiovascular disease (CVD) outcomes simultaneously. We sought to characterize the competing incidences for subtypes of first CVD events or non-CVD death in those with and without ECG LVH.
We included participants in the Atherosclerosis Risk in Communities (ARIC) study. ECG LVH was defined according to Sokolow-Lyon criteria. We used competing Cox models to compare hazards for diverse outcomes within groups (e.g., among those with ECG LVH) and for a given event between groups (ECG LVH versus no ECG LVH).
After 15 years, men with ECG LVH at baseline (N = 383) had cumulative incidence of first CVD events and non-CVD deaths of 29.2% and 6.1%, respectively (hazard ratio 4.86; 95% CI, 3.04–7.77). In men without ECG LVH (N = 6576) the incidence of any first CVD event and non-CVD death was 18.9% and 6.9%, respectively (hazard ratio 2.67; 2.39–2.98). Similar associations were observed in women (N = 381 with and N = 8187 without ECG LVH). Coronary heart disease (CHD) was the most common first event in men with ECG LVH (15.0%) and heart failure (HF) was the most common first event in women with ECG LVH (10.5%). After adjustment for risk factors including systolic blood pressure, any CVD event remained the most likely first event.
Among middle-aged individuals with ECG LVH, the most likely first events are CHD in men and HF in women; these results may have implications for preventive approaches.
left ventricular hypertrophy; cardiovascular disease; coronary heart disease; stroke; heart failure
Understanding how sex and tobacco exposure may modify lifetime risks for cancer mortality is important for effective communication of risk in targeted public health messages.
To determine lifetime risk estimates for cancer death associated with sex and smoking status in the United States.
A pooled cohort design using ten well-defined epidemiologic cohorts including middle-aged and older individuals was used to estimate the lifetime risk for cancer death at selected index ages, with death from non-cancer causes as the competing risk, by sex and smoking status.
There were a total of 11,317 cancer-related deaths. At age 45 years, the lifetime risk of cancer death for male smokers is 27.7% (95% CI 24.0% to 31.4%) compared to 15.8% (95% CI 12.7% to 18.9%) for male non-smokers. At age 45 years, the lifetime risk of cancer death for female smokers is 21.7% (95% CI 18.8% to 24.6%) compared to 13.2% (95% CI 11.0% to 15.4%) for female non-smokers. Remaining lifetime risk for cancer death declined with age, and men have a greater risk for cancer death compared to women. Adjustment for competing risk of death, particularly representing cardiovascular mortality, yielded a greater change in lifetime risk estimates for men and smokers compared to women and non-smokers.
At the population level the lifetime risk for cancer death remains significantly higher for smokers compared to non-smokers, regardless of sex. These estimates may provide clinicians with useful information for counseling individual patients and highlight the need for continued public health efforts related to smoking cessation.
Tobacco; Smoking; Cancer; Lifetime Risk; Cancer mortality; Sex
Religious involvement has been associated with improved health outcomes but greater obesity in older adults. No longitudinal study of young adults has examined the prospective association of religious involvement with incident cardiovascular risk factors (RFs) and subclinical disease (subCVD).
We included 2433 participants of the CARDIA study, aged 20 to 32 in 1987 when religiosity was assessed, who were followed for 18 years. Multivariable-adjusted regression models were fitted to assess prospective associations of frequency of religious participation at baseline with incidence of RFs and prevalence of subCVD after 18 years’ follow up.
High frequency of religious participation was associated with a significantly greater incidence of obesity in unadjusted models (RR 1.57, 95% CI 1.14 – 1.73) and demographic-adjusted models (RR 1.34, 95% CI 1.09 – 1.65) but not after additional adjustment for baseline RFs (RR 1.17, 95% CI 0.97 – 1.41). When religious participation was treated dichotomously, any religious participation, compared with none, was associated with significantly lower subCVD.
Frequent religious participants are more likely to become obese between young adulthood and middle age; this association is confounded by demographic and other factors. Nonetheless, young adults with frequent participation may represent an opportunity for obesity prevention.
Religion; Cardiovascular Disease; Obesity; Epidemiology; Prevention
The association between measures of arterial compliance and peripheral arterial disease (PAD) is unclear. Early changes in arterial wall compliance could be a useful marker of patients at high risk for developing lower extremity atherosclerosis.
We used linear and logistic regression models on baseline data from 2803 female and 2558 male participants in the Multi-Ethnic Study of Atherosclerosis (MESA) to study associations between tonometry-derived baseline measures of arterial compliance (large artery compliance [C1] and small artery compliance [C2]) and the baseline ankle-brachial index (ABI), as well as change in the ABI over approximately 3 years of follow up.
In cross-sectional analyses, lower C1 and C2 values, indicating poorer arterial compliance, were associated with lower ABI. There were significant linear trends across strata of ABI, especially in C2 which ranged from 3.7ml/mmHg × 100 (95% confidence interval (CI) 3.3 to 4.2) in women with an ABI < 0.90 to 4.2ml/mmHg × 100 (95% CI 4.1 to 4.3 p<0.001) in women with ABI 1.10 - <1.40. Similar significant trends (p<0.001) were seen in men. In prospective analyses, those with the lowest tertile of C2 values at baseline had a greater multivariable-adjusted odds for decline in ABI of ≥ 0.15 over 3 years compared to those with the highest C2 values at baseline (OR 1.80 95% CI 1.23–2.64).
We observed that less compliant arteries were significantly associated with low ABI in cross-sectional analysis and with greater decline in ABI over time.
Ankle-Brachial Index; Arterial Compliance; Peripheral Arterial Disease
No studies have compared first CVD events and non-CVD death between races in a competing risks framework, which examines risks for numerous events simultaneously.
Methods and Results
We used competing Cox models to estimate hazards for first CVD events and non-CVD death within and between races in three multi-center, NHLBI-sponsored cohorts. Of 14569 ARIC study participants aged 45–64y with mean follow up of 10.5y, 11.6% had CVD and 5.0% had non-CVD death as first events; among 4237 CHS study participants aged 65–84y and followed for 8.5y, these figures were 43.2% and 15.7%, respectively. Middle-aged blacks were significantly more likely than whites to experience any CVD as a first event; this disparity disappeared by older adulthood and after adjustment for CVD risk factors. The pattern of results was similar for MESA participants. Traditional Cox and competing risks models yielded different results for CHD risk. Black men appeared somewhat more likely than white men to experience CHD using a standard Cox model (HR 1.06; 95% CI 0.90, 1.26) whereas they appeared less likely than white men to have a first CHD event using a competing risks model (HR 0.77; 95% CI 0.60, 1.00).
CVD affects blacks at an earlier age than whites; this may be partially attributable to elevated CVD risk factor levels among blacks. Racial disparities in first CVD incidence disappear by older adulthood. Competing risks analyses may yield somewhat different results than traditional Cox models and provide a complementary approach to examining risks for first CVD events.
cardiovascular diseases; epidemiology; prevention; risk factors; survival
To detect differences in potential magnetic resonance (MR) imaging biomarkers of coronary remodeling between older hypertensive patients and healthy controls
Methods and results
Two-dimensional black-blood coronary wall MR imaging and three-dimensional whole-heart coronary MR angiography were performed on 130 participants (65–84 years), including 65 hypertensive patients and 65 healthy controls. Coronary segments derived from hypertensive participants had a higher mean coronary wall thickness, a smaller vessel area, a smaller coronary wall area, a smaller lumen area, a lower coronary distensibilit index (CDI) and a higher percent of the coronary wall occupying the vessel area (PWOV) than those from healthy controls. When the average PWOV was set as an ad hoc cutoff point, coronary segments with a high PWOV had a significantly higher mean wall thickness, a higher maximum wall thickness, a smaller vessel area, a smaller lumen area, a lower CDI and a higher coronary plaque index (CPI) compared with coronary segments with a low PWOV.
MR techniques are able to noninvasively detect significant differences in potential imaging biomarkers of coronary remodeling between older hypertensive patients and healthy aging controls. The PWOV is a promising remodeling feature for quantitatively evaluating the progression of coronary atherosclerosis.
MR imaging; coronary remodeling; imaging biomarker; hypertension
Many patients exhibit multiple chronic disease risk behaviors. Research provides little information about advice that can maximize simultaneous health behavior changes.
To test which combination of diet and activity advice maximizes healthy change, we randomized 204 adults with elevated saturated fat and low fruit/vegetable intakes, high sedentary leisure time and low physical activity to one of four treatments: increase fruit/vegetable and physical activity; decrease fat and sedentary leisure; decrease fat and increase physical activity; increase fruit/vegetable and decrease sedentary leisure. Treatments provided three weeks of remote coaching supported by mobile decision support technology and financial incentives. During treatment, incentives were contingent on using the mobile device to self-monitor and attain behavioral targets; during follow-up they were contingent only on recording. The outcome was standardized, composite improvement on the four diet and activity behaviors at end of treatment and five month follow-up.
Of those randomized, 200 (98%) completed follow-up. The increase fruit/vegetable and decrease sedentary leisure treatment improved more than the other 3 treatments (p<.001). Specifically, fruit/vegetables increased from 1.2 servings/day to 5.5; sedentary leisure decreased from 219.2 minutes/day to 89.3; saturated fat decreased from 12.0% of calories consumed to 9.5%. Differences between treatment groups were maintained through follow-up. Traditional dieting (decrease fat and increase physical activity) improved less than the other 3 treatments (p<.001).
Remote coaching supported by mobile technology and financial incentives holds promise to improve diet and activity. Targeting fruits/vegetables and sedentary leisure together maximizes overall adoption and maintenance of multiple healthy behavior changes.
Pregnancy is associated with marked maternal cardiovascular/hemodynamic changes. A greater number of pregnancies may be associated with long-term subclinical changes in left ventricular (LV) remodeling.
Among 2,234 white, black, Hispanic, and Chinese women (mean age 62 years) in the MESA, we used linear regression to relate live births and cardiac magnetic resonance imaging LV measures. Covariates included age, ethnicity, height, income, education, birth country, smoking, menopause, and oral contraceptive duration. Models were additionally adjusted for potential mediators: systolic blood pressure, antihypertensive use, total/high-density lipoprotein cholesterol, triglycerides, diabetes, and body mass index. We performed sensitivity analyses excluding 763 women in the lowest socioeconomic group: annual income <$25,000 and lower high school level of education.
With each live birth, LV mass increased 1.26 g; LV end-diastolic volume, 0.74 mL; and LV end-systolic volume, 0.45 mL; LV ejection fraction decreased 0.18% (P trend <0.05). Changes were most notable for the category of women with ≥5 pregnancies. Upon adjustment for potential biologic mediators, live births remained positively associated with LV mass and end-systolic volume. Live births remained significantly associated with LV end-systolic, end-diastolic volumes, and LV mass (P trend ≤0.02) after excluding women in the lowest socioeconomic group.
Number of live births is associated with key LV structural and functional measures in middle to older ages, even after adjustment for sociodemographic factors and cardiovascular disease risk factors. Hemodynamic changes during pregnancy may be associated with cardiac structure/function beyond childbearing years.
To estimate the effect of education and income on incident heart failure (HF) hospitalization among post-menopausal women.
Investigations of socioeconomic status (SES) have focused on outcomes after HF diagnosis, not associations with incident HF. We used data from the Women’s Health Initiative Hormone Trials to examine the association between SES levels and incident HF hospitalization.
We included 26,160 healthy, post-menopausal women. Education and income were self-reported. ANOVA, Chi-square tests, and proportional hazards models were used for statistical analysis, with adjustment for demographics, co-morbid conditions, behavioral factors, and hormone and dietary modification assignments.
Women with household incomes <$20,000/year had higher HF hospitalization incidence (57.3/10,000 person-years) than women with household incomes >$50,000/year (16.7/10,000 person-years; p<0.01). Women with less than a high school education had higher HF hospitalization incidence (51.2/10,000 person-years) than college graduates and above (25.5/10,000 person-years; p<0.01). In multivariable analyses, women with the lowest income levels had 56% higher risk (HR 1.56, 95% CI 1.19 to 2.04) than the highest income women; women with the least amount of education had 21% higher risk for incident HF hospitalization (HR 1.21, 95% CI 0.90 to 1.62) than the most educated women.
Lower income is associated with an increased incidence of HF hospitalization among healthy, post-menopausal women, whereas multivariable adjustment attenuated the association of education with incident HF.
heart failure; socioeconomic status; women
To determine the association between fitness and lifetime risk for cardiovascular disease (CVD).
Higher levels of traditional risk factors are associated with marked differences in lifetime risks for CVD. However, data are sparse regarding the association between fitness and the lifetime risk for CVD.
We followed 11,049 men who underwent clinical examination at the Cooper Clinic in Dallas, TX before 1990 until the occurrence of CVD death, non-CVD death, or attainment of age 90 (281,469 person-years of follow-up, median follow-up 25.3 years, 1,106 CVD deaths). Fitness was measured by Balke protocol and categorized according to treadmill time into low-, intermediate-, and high- fitness with further stratification by CVD risk factor burden. Lifetime risk for CVD death determined by the National Death Index was estimated for fitness levels measured at ages 45-, 55-, and 65-years with non-CVD death as the competing event.
Differences in fitness levels (low- fitness versus high- fitness) were associated with marked differences in the lifetime risks for CVD death at each index age (age 45: 13.7% versus 3.4%; age 55: 34.2% versus 15.3%; age 65: 35.6% versus 17.1%). These associations were strongest among individuals with CVD risk factors.
A single measurement of low fitness in mid-life was associated with higher lifetime risk for CVD death, particularly among individuals with a high burden of CVD risk factors.
cardiovascular disease; epidemiology; exercise testing; lifetime risk
The lifetime risks of cardiovascular disease have not been reported across the age spectrum in black adults and white adults.
We conducted a meta-analysis at the individual level using data from 18 cohort studies involving a total of 257,384 black men and women and white men and women whose risk factors for cardiovascular disease were measured at the ages of 45, 55, 65, and 75 years. Blood pressure, cholesterol level, smoking status, and diabetes status were used to stratify participants according to risk factors into five mutually exclusive categories. The remaining lifetime risks of cardiovascular events were estimated for participants in each category at each age, with death free of cardiovascular disease treated as a competing event.
We observed marked differences in the lifetime risks of cardiovascular disease across risk-factor strata. Among participants who were 55 years of age, those with an optimal risk-factor profile (total cholesterol level, <180 mg per deciliter [4.7 mmol per liter]; blood pressure, <120 mm Hg systolic and 80 mm Hg diastolic; nonsmoking status; and nondiabetic status) had substantially lower risks of death from cardiovascular disease through the age of 80 years than participants with two or more major risk factors (4.7% vs. 29.6% among men, 6.4% vs. 20.5% among women). Those with an optimal risk-factor profile also had lower lifetime risks of fatal coronary heart disease or nonfatal myocardial infarction (3.6% vs. 37.5% among men, <1% vs. 18.3% among women) and fatal or nonfatal stroke (2.3% vs. 8.3% among men, 5.3% vs. 10.7% among women). Similar trends within risk-factor strata were observed among blacks and whites and across diverse birth cohorts.
Differences in risk-factor burden translate into marked differences in the lifetime risk of cardiovascular disease, and these differences are consistent across race and birth cohorts. (Funded by the National Heart, Lung, and Blood Institute.)
Data are sparse describing factors associated with development of prolonged QRS duration (QRSd) from young adulthood to middle age.
We analyzed 12-lead electrocardiograms (ECGs) from the Coronary Artery Risk Development in Young Adults (CARDIA) study over 20 years. We performed logistic regression to examine associations of baseline (Year 0) or average (Year 0 to Year 20) risk factors with incident prolonged QRSd (QRS > 100 msec).
We included 2,537 participants (57.2% women, 44.7% black, mean age 25 years); 292 (11.5%) developed incident QRSd >100 msec by Year 20. In univariate analyses, baseline covariates associated with incident QRSd prolongation included white race, male sex, ECG-LVMI, and baseline QRSd. Similar results were observed after multivariable adjustment.
We found no long-term associations of modifiable risk factors with incident QRSd >100 msec. Men, whites, and those with higher ECG-LVMI and QRSd in young adulthood are at increased risk for incident prolonged QRSd by middle age.
A low cardiovascular disease (CVD) risk profile (untreated cholesterol < 200 mg/dl, untreated blood pressure < 120/<80 mmHg, never smoking, and no history of diabetes and myocardial infarction) in middle age is associated with markedly better health outcomes in older age, but few middle aged adults have this low risk profile. We examined whether adopting a healthy lifestyle throughout young adulthood is associated with presence of the low CVD risk profile in middle age.
Methods and Results
The CARDIA study sample consisted of 3,154 black and white participants aged 18 to 30 years at Year 0 (Y0, 1985-86) who attended the Year 0, 7 and 20 (Y0, Y7 and Y20) examinations. Healthy lifestyle factors (HLFs) defined at Y0, Y7 and Y20 included: 1) Average BMI < 25 kg/m2; 2) No or moderate alcohol intake; 3) higher healthy diet score; 4) higher physical activity score; and 5) Never smoking. Mean age (25 years) and percentage of women (56%) were comparable across groups defined by number of HLFs. The age-, sex- and race-adjusted prevalences of low CVD risk profile at Y20 were 3.0%, 14.6%, 29.5%, 39.2% and 60.7% for people with 0 or 1, 2, 3, 4, and 5 HLFs, respectively (p-trend <0.0001). Similar graded relationships were observed for each sex-race group (all p-trend<0.0001).
Maintaining a healthy lifestyle throughout young adulthood is strongly associated with low CVD risk profile in middle age. Public health and individual efforts are needed to improve adoption and maintenance of healthy lifestyles in young adults.
epidemiology; follow-up studies; risk factors; prevention
Few studies to date have described the prevalence of electrocardiographic (ECG) abnormalities in a biracial middle-aged cohort.
Methods and Results
Participants underwent measurement of traditional risk factors and 12-lead ECGs coded using both Minnesota Code (MC) and Novacode (NC) criteria. Among 2585 participants, of whom 57% were women and 44% were black (mean age 45 years), the prevalence of major and minor abnormalities were significantly higher (all P<0.001) among black men and women compared to whites. These differences were primarily due to higher QRS voltage and ST/T wave abnormalities among blacks. There was also a higher prevalence of Q waves (MC 1-1, 1-2, 1-3) than described by previous studies. These racial differences remained after multivariate adjustment for traditional cardiovascular (CV) risk factors.
Black men and women have a significantly higher prevalence of ECG abnormalities, independent of traditional CV risk factors, than whites in a contemporary cohort middle-aged participants.
We sought to determine whether novel markers not involving ionizing radiation could predict CAC progression in a low-risk population.
Increase in coronary artery calcium (CAC) scores over time (CAC progression) improves prediction of coronary heart disease (CHD) events. Due to radiation exposure, CAC measurement represents an undesirable method for repeated risk assessment, particularly in low predicted risk individuals (Framingham Risk Score [FRS] <10%).
From 6814 MESA participants, 2620 individuals were classified as low risk for CHD events (FRS <10%), and had follow-up CAC measurement. In addition to traditional risk factors [(RFs) - base model], various combinations of novel-marker models were selected based on data-driven, clinical, or backward stepwise selection techniques.
Mean follow-up was 2.5 years. CAC progression occurred in 574 participants (22% overall; 214 of 1830 with baseline CAC =0, and 360 of 790 with baseline CAC >0). Addition of various combinations of novel markers to the base model (c-statistic =0.711), showed improvements in discrimination of approximately only 0.005 each (c-statistics 0.7158, 0.7160 and 0.7164) for the best-fit models. All 3 best-fit novel-marker models calibrated well but were similar to the base model in predicting individual risk probabilities for CAC progression. The highest prevalence of CAC progression occurred in the highest compared to the lowest probability quartile groups (39.2–40.3% versus 6.4–7.1%).
In individuals at low predicted risk by FRS, traditional RFs predicted CAC progression in the short term with good discrimination and calibration. Prediction improved minimally when various novel markers were added to the model.
coronary calcium; Framingham risk score; risk factors; progression
Religious involvement has been associated with improved health practices and outcomes; however, no ethnically-diverse community-based study has examined differences in cardiac risk factors, subclinical cardiovascular disease, and cardiovascular disease (CVD) events across levels of religiosity.
Methods and Results
We included 5474 White, Black, Hispanic, and Chinese participants who attended Exam 2 of the NHLBI’s MESA study. We compared cross-sectional differences in cardiac risk factors and subclinical CVD, and longitudinal CVD event rates across self-reported levels of religious participation, prayer/meditation, and spirituality. Multivariable-adjusted regression models were fitted to assess associations of measures of religiosity with risk factors, subclinical CVD, and CVD events. MESA participants (52.4% female, mean age 63) with greater levels of religious participation were more likely to be female and black. After adjustment for demographic covariates, participants who attended services daily, compared with never, were significantly more likely to be obese (adjusted odds ratio 1.57, 95% confidence interval [CI] 1.12 – 1.72), but less likely to smoke (adjusted odds ratio 0.39, 95% CI 0.26 – 0.58). Results were similar for those with frequent prayer/meditation or high levels of spirituality. There were no consistent patterns of association observed between measures of religiosity and presence/extent of subclinical CVD at baseline or incident CVD events during longitudinal follow up over 4 years.
Our results do not confirm those of previous studies associating greater religiosity with overall better health risks and status, at least with regard to CVD. There was no reduction in risk for CVD events associated with greater religiosity.
Religion; Cardiovascular diseases; Obesity
Prior estimates of lifetime risk (LTR) for cardiovascular disease (CVD) examined the impact of blood pressure at the index age and did not account for changes in blood pressure over time. We examined how changes in blood pressure during middle-age affect LTR for CVD, coronary heart disease (CHD) and stroke.
Methods and Results
Data from 7 diverse US cohort studies were pooled. Remaining LTR for CVD, CHD and stroke were estimated for White and Black men and women with death free of CVD as a competing event. LTR for CVD by blood pressure (BP) strata and by changes in BP over an average of 14 years were estimated. Starting at age 55, we followed 61,585 men and women for 700,000 person-years. LTR for CVD was 52.5% (95% CI 51.3–53.7) for men and 39.9% (38.7–41.0) for women. LTR for CVD was higher for Blacks and increased with increasing BP at index age. Individuals who maintained or decreased their BP to normal levels had the lowest remaining LTR for CVD, 22–41%, as compared to individuals who had or developed hypertension by the age of 55, 42–69%; suggesting a dose-response effect for the length of time at high BP levels
Individuals who experience increases or decreases in BP in middle age have associated higher and lower remaining LTR for CVD. Prevention efforts should continue to emphasize the importance of lowering BP and avoiding or delaying the incidence of hypertension in order to reduce the LTR for CVD.
cardiovascular disease; coronary heart disease; stroke; hypertension; risk factors
Data are sparse regarding the long-term association of favorable levels of all major cardiovascular disease risk factors (RFs) (ie, low risk [LR]) with ankle-brachial index (ABI).
Methods and Results
In 2007–2010, the Chicago Healthy Aging Study reexamined a subset of participants aged 65 to 84 years from the Chicago Heart Association Detection Project in Industry cohort (baseline examination, 1967–1973). RF groups were defined as LR (untreated blood pressure ≤120/≤80 mm Hg, untreated serum cholesterol <200 mg/dL, body mass index <25 kg/m2, not smoking, no diabetes) or as 0 RFs, 1 RF, or 2+ RFs based on the presence of blood pressure ≥140/≥90 mm Hg or receiving treatment, serum cholesterol ≥240 mg/dL or receiving treatment, body mass index ≥30 kg/m2, smoking, or diabetes. ABI at follow-up was categorized as indicating PAD present (≤0.90), as borderline PAD (0.91 to 0.99), or as normal (1.00 to 1.40). We included 1346 participants with ABI ≤1.40. After multivariable adjustment, the presence of fewer baseline RFs was associated with a lower likelihood of PAD at 39-year follow-up (P for trend is <0.001). Odds ratios (95% CIs) for PAD in persons with LR, 0 RFs, or 1 RF compared with those with 2+ RFs were 0.14 (0.05 to 0.44), 0.28 (0.13 to 0.59), and 0.33 (0.16 to 0.65), respectively; findings were similar for borderline PAD (P for trend is 0.005). The association was mainly due to baseline smoking status, cholesterol, and diabetes. Remaining free of adverse RFs or improving RF status over time was also associated with PAD.
LR profile in younger adulthood (ages 25 to 45) is associated with the lowest prevalence of PAD and borderline PAD 39 years later.
aging; atherosclerosis; cardiovascular disease; peripheral artery disease; risk factors
We sought to determine the levels of risk factors required to exceed threshold values of intermediate (≥10%) or high (>20%) predicted 10-year risk for coronary heart disease using the Adult Treatment Panel III (ATP-III) Risk Assessment Tool.
Continuous risk factor values were entered into the risk assessment tool to examine levels of predicted 10-year risk. Both individual risk factors and the joint effects of varying multiple risk factors were systematically examined.
Women only exceed 10% risk at ages ≥70 with single risk factors of HDL-cholesterol levels <30 mg/dL or systolic blood pressure >170 mm Hg. Women ≤65 only exceed 10% risk if they are smokers with low HDL-cholesterol levels. In contrast, single risk factors can cause men over 45 to exceed 10% or 20% predicted 10-year risk. Combinations of only modestly elevated risk factors cause many men to exceed 10% risk at ages ≥45, and to exceed 20% risk at ages ≥55.
Because such high risk factor levels are required for men <45 years and women <65 years to exceed ATP-III risk thresholds, additional means for risk communication may be needed for individuals with elevated risk factors in these age ranges.
risk factors; primary prevention; risk prediction; coronary heart disease
Accurate risk prediction is an important step in developing optimal strategies for disease prevention and treatment. Based on the predicted risks, patients can be stratified to different risk categories where each category corresponds to a particular clinical intervention. Incorrect or suboptimal interventions are likely to result in unnecessary financial and medical consequences. It is thus essential to account for the costs associated with the clinical interventions when developing and evaluating risk stratification (RS) rules for clinical use. In this article, we propose to quantify the value of an RS rule based on the total expected cost attributed to incorrect assignment of risk groups due to the rule. We have established the relationship between cost parameters and optimal threshold values used in the stratification rule that minimizes the total expected cost over the entire population of interest. Statistical inference procedures are developed for evaluating and comparing given RS rules and examined through simulation studies. The proposed procedures are illustrated with an example from the Cardiovascular Health Study.
Disease prognosis; Optimal risk stratification; Risk prediction
The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated.
Methods and Results
We examined a panel of approximately 50,000 common single nucleotide polymorphisms (SNPs) in 2,095 cardiovascular candidate genes and AF in three cohorts with participants of European (n=18,524; 2,260 cases) or African American descent (n=3,662; 263 cases) in the National Heart Lung and Blood Institute's Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n= 19,602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk (RR) C allele, 0.90; 95% confidence interval (CI), 0.85–0.95; P=0.0005) in whites, but did not reach statistical significance in African Americans (RR, 0.86; 95% CI, 0.72–1.03; P=0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95% CI, 0.57–0.89; P=0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994, hazard ratio, 1.40; 95% CI, 1.16–1.69; P=0.0005).
In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans.
atrial fibrillation; single nucleotide polymorphism; epidemiology; cohort study; race/ethnicity
We tested the ability of the Framingham Risk Score (FRS) and the online ATP III risk estimator to estimate risk and to predict 10-year and longer term coronary heart disease (CHD) death in younger adults (age 18–39 years). Although prediction with individual risk factors has been tested in individuals less than 30 years, current multivariate risk prediction strategies have not been applied to prediction of clinical CHD in this age range.
We included 10,551 male participants of the Chicago Heart Association Detection Project in Industry (CHA) who were ages 18 to 39 years and free of baseline CHD and diabetes at enrollment in 1967–1973. CHD risk was estimated using both FRS and ATP-III online risk estimator for each individual. Men were stratified into deciles according to the magnitude of predicted risk calculated from measured baseline risk factors (CHA-predicted risk). Observed CHD mortality rates for 10-, 20-, and 30-years of follow-up were compared with estimated risks. CHD death rates were low across 30-years of follow-up.
The Framingham Risk Score remained below 10% for all deciles of CHA-predicted risk in the 18 to 29 year old cohort. Framingham-predicted risk reached 12% only in the 30 to 39 year old cohort in the highest decile of CHA-predicted risk, despite substantial risk factor burden.
Neither method classified individuals under 30 years of age as high risk despite substantial risk factor burden. Future clinical guidelines should consider alternative strategies to estimate and communicate risk in populations below age 30.
By examining the distribution of CAC across FRS strata in a large, multi-ethnic, community-based sample of men and women, we sought to determine if lower risk persons could potentially benefit from CAC screening.
The 10-year Framingham risk scores (FRS) and coronary artery calcium (CAC) are predictors of coronary heart disease (CHD). CAC ≥300 is associated with the highest risk for CHD even in low risk (FRS <10%) persons; however expert groups have suggested CAC screening only in intermediate risk (FRS 10–20%) groups.
We included 5660 MESA participants. The number needed to screen [number of people that need to be screened to detect one person with CAC above the specified cut-point (NNS)] was used to assess the yield of screening for CAC. CAC prevalence was compared across FRS strata using chi-square tests.
CAC >0, ≥100 and ≥300 were present in 46.4%, 20.6% and 10.1% of participants, respectively. Prevalence and amount of CAC increased with higher FRS. CAC ≥300 was observed in 1.7% and 4.4% of those with FRS 0–2.5% and 2.6–5%, respectively (NNS =59.7 and 22.7). Likewise, CAC ≥300 was observed in 24% and 30% of those with FRS 15.1–20% and >20%, respectively (NNS =4.2 and 3.3). Trends were similar when stratified by age, gender and race/ethnicity.
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 5.1–20%).
Framingham risk score; coronary calcium; coronary heart disease; number needed to screen; risk factors; population; atherosclerosis; low risk
AHA Scientific Statements; cardiovascular diseases; prevention; risk factors; women; guidelines; cost-effectiveness