OBJECTIVE
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.
DESIGN
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).
RESULTS
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.
CONCLUSIONS
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.
doi:10.1136/heartjnl-2011-300819
PMCID: PMC3569012
PMID: 22139711
left ventricular hypertrophy; cardiovascular disease; coronary heart disease; stroke; heart failure
Background
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).
Methods
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.
Results
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.
Conclusions
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.
doi:10.1016/j.ypmed.2011.11.004
PMCID: PMC3310238
PMID: 22155479
Religion; Cardiovascular Disease; Obesity; Epidemiology; Prevention
Background
Data are sparse describing factors associated with development of prolonged QRS duration (QRSd) from young adulthood to middle age.
Methods
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).
Results
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.
Conclusion
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.
doi:10.1016/j.jelectrocard.2011.11.001
PMCID: PMC3542388
PMID: 22197105
Background
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).
Conclusions
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.
doi:10.1161/CIRCULATIONAHA.111.060681
PMCID: PMC3353808
PMID: 22291127
epidemiology; follow-up studies; risk factors; prevention
Walsh, Joseph A | Prineas, Ronald | Daviglus, Martha L. | Ning, Hongyan | Liu, Kiang | Lewis, Cora E. | Sidney, Steven | Schreiner, Pamela J. | Iribarren, Carlos | Lloyd-Jones, Donald M.
Background
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.
Conclusions
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.
doi:10.1016/j.jelectrocard.2010.02.001
PMCID: PMC3569004
PMID: 20374967
Objectives
We sought to determine whether novel markers not involving ionizing radiation could predict CAC progression in a low-risk population.
Background
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%).
Methods
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.
Results
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%).
Conclusions
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.
doi:10.1016/j.jcmg.2011.11.008
PMCID: PMC3310187
PMID: 22340820
coronary calcium; Framingham risk score; risk factors; progression
Background
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
Conclusions
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.
doi:10.1161/CIRCULATIONAHA.110.002774
PMCID: PMC3310202
PMID: 22184621
cardiovascular disease; coronary heart disease; stroke; hypertension; risk factors
Berry, Jarett D. | Dyer, Alan | Cai, Xuan | Garside, Daniel B. | Ning, Hongyan | Thomas, Avis | Greenland, Philip | Van Horn, Linda | Tracy, Russell P. | Lloyd-Jones, Donald M.
BACKGROUND
The lifetime risks of cardiovascular disease have not been reported across the age spectrum in black adults and white adults.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.)
doi:10.1056/NEJMoa1012848
PMCID: PMC3336876
PMID: 22276822
Background
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.
Conclusions
LR profile in younger adulthood (ages 25 to 45) is associated with the lowest prevalence of PAD and borderline PAD 39 years later.
doi:10.1161/JAHA.112.001545
PMCID: PMC3540658
PMID: 23316312
aging; atherosclerosis; cardiovascular disease; peripheral artery disease; risk factors
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.
doi:10.1093/biostatistics/kxr001
PMCID: PMC3169667
PMID: 21415016
Disease prognosis; Optimal risk stratification; Risk prediction
Schnabel, Renate B. | Kerr, Kathleen F. | Lubitz, Steven A. | Alkylbekova, Ermeg L. | Marcus, Gregory M. | Sinner, Moritz F. | Magnani, Jared W. | Wolf, Philip A. | Deo, Rajat | Lloyd-Jones, Donald M. | Lunetta, Kathryn L. | Mehra, Reena | Levy, Daniel | Fox, Ervin R. | Arking, Dan E. | Mosley, Thomas H. | Mueller, Martina | Young, Taylor | Wichmann, Erich | Seshadri, Sudha | Farlow, Deborah N. | Rotter, Jerome I. | Soliman, Elsayed Z. | Glazer, Nicole L. | Wilson, James G. | Breteler, Monique M.B. | Sotoodehnia, Nona | Newton-Cheh, Christopher | Kääb, Stefan | Ellinor, Patrick T. | Alonso, Alvaro | Benjamin, Emelia J. | Heckbert, Susan R.
Background
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).
Conclusions
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.
doi:10.1161/CIRCGENETICS.110.959197
PMCID: PMC3224824
PMID: 21846873
atrial fibrillation; single nucleotide polymorphism; epidemiology; cohort study; race/ethnicity
Background
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.
Conclusions
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.
doi:10.1161/CIRCULATIONAHA.109.879973
PMCID: PMC2871276
PMID: 20100975
Religion; Cardiovascular diseases; Obesity
Objectives
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.
Background
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.
Methods
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.
Results
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.
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 5.1–20%).
doi:10.1016/j.jacc.2010.11.053
PMCID: PMC3268231
PMID: 21527159
Framingham risk score; coronary calcium; coronary heart disease; number needed to screen; risk factors; population; atherosclerosis; low risk
Objective
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1016/j.ypmed.2008.07.012
PMCID: PMC2630457
PMID: 18718484
risk factors; primary prevention; risk prediction; coronary heart disease
Mosca, Lori | Benjamin, Emelia J. | Berra, Kathy | Bezanson, Judy L. | Dolor, Rowena J. | Lloyd-Jones, Donald M. | Newby, L. Kristin | Piña, Ileana L. | Roger, Véronique L. | Shaw, Leslee J. | Zhao, Dong | Beckie, Theresa M. | Bushnell, Cheryl | D’Armiento, Jeanine | Kris-Etherton, Penny M. | Fang, Jing | Ganiats, Theodore G. | Gomes, Antoinette S. | Gracia, Clarisa R. | Haan, Constance K. | Jackson, Elizabeth A. | Judelson, Debra R. | Kelepouris, Ellie | Lavie, Carl J. | Moore, Anne | Nussmeier, Nancy A. | Ofili, Elizabeth | Oparil, Suzanne | Ouyang, Pamela | Pinn, Vivian W. | Sherif, Katherine | Smith, Sidney C. | Sopko, George | Chandra-Strobos, Nisha | Urbina, Elaine M. | Vaccarino, Viola | Wenger, Nanette K.
doi:10.1016/j.jacc.2011.02.005
PMCID: PMC3124072
PMID: 21388771
AHA Scientific Statements; cardiovascular diseases; prevention; risk factors; women; guidelines; cost-effectiveness
Okwuosa, Tochi M. | Greenland, Philip | Lakoski, Susan G. | Ning, Hongyan | Kang, Joseph | Blumenthal, Roger S. | Szklo, Moyses | Crouse, John R. | Lima, Joao A. C. | Liu, Kiang | Lloyd-Jones, Donald M.
Even among asymptomatic people at low risk (<10%) by Framingham Risk Score (FRS), high coronary artery calcium (CAC) scores signify higher predicted risk of coronary heart disease (CHD) events. We sought to determine non-invasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3046 participants from MESA at low 10-year predicted risk (FRS <10%) for CHD events. Multivariable logistic regression was used to assess the association of novel markers with presence of any CAC (CAC >0) and advanced CAC (CAC ≥ 300). CAC >0 and CAC ≥ 300 were present in 30% and 3.5% of participants, respectively. Factor VIIIc, fibrinogen and sICAM were each associated with CAC presence (P ≤ 0.02); and C-reactive protein, D-dimer and carotid intima-media thickness (CIMT) with advanced CAC (P ≤ 0.03). The base model combining traditional risk factors had excellent discrimination for advanced CAC (C-statistic, 0.808). Addition of the 2 best-fit models combining biomarkers plus/minus CIMT improved the c-statistics to 0.822 and 0.820, respectively. All 3 models calibrated well, but were similar in estimating individual risk probabilities for advanced CAC (prevalence = 9.97%, 10.63% and 10.10% in the highest quartiles of predicted probabilities versus 0.26%, 0.26% and 0.26% in the lowest quartiles, respectively). In conclusion, in low risk individuals, traditional risk factors alone predicted advanced CAC with high discrimination and calibration. Biomarker combinations +/− CIMT were also significantly associated with advanced CAC, but improvement in prediction and estimation of clinical risk were modest compared to traditional risk factors alone.
doi:10.1016/j.amjcard.2010.10.072
PMCID: PMC3182475
PMID: 21376929
coronary calcium; biomarkers; novel markers; low-risk; risk factors
doi:10.1186/1532-429X-14-S1-P171
PMCID: PMC3305011
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1016/j.ahj.2007.03.042
PMCID: PMC2279177
PMID: 17584558
Mosca, Lori | Benjamin, Emelia J. | Berra, Kathy | Bezanson, Judy L. | Dolor, Rowena J. | Lloyd-Jones, Donald M. | Newby, L. Kristin | Piña, Ileana L. | Roger, Véronique L. | Shaw, Leslee J. | Zhao, Dong | Beckie, Theresa M. | Bushnell, Cheryl | D’Armiento, Jeanine | Kris-Etherton, Penny M. | Fang, Jing | Ganiats, Theodore G. | Gomes, Antoinette S. | Gracia, Clarisa R. | Haan, Constance K. | Jackson, Elizabeth A. | Judelson, Debra R. | Kelepouris, Ellie | Lavie, Carl J. | Moore, Anne | Nussmeier, Nancy A. | Ofili, Elizabeth | Oparil, Suzanne | Ouyang, Pamela | Pinn, Vivian W. | Sherif, Katherine | Smith, Sidney C. | Sopko, George | Chandra-Strobos, Nisha | Urbina, Elaine M. | Vaccarino, Viola | Wenger, Nanette K.
doi:10.1161/CIR.0b013e31820faaf8
PMCID: PMC3182143
PMID: 21325087
AHA Scientific Statements; cardiovascular diseases; prevention; risk factors; women; guidelines; cost-effectiveness
Ekundayo, O. James | Dell’Italia, Louis J. | Sanders, Paul W. | Arnett, Donna | Aban, Inmaculada | Love, Thomas E. | Filippatos, Gerasimos | Anker, Stefan D. | Lloyd-Jones, Donald M. | Bakris, George | Mujib, Marjan | Ahmed, Ali
Background
The association between hyperuricemia and incident heart failure (HF) is relatively unknown.
Methods
Of the 5461 community-dwelling older adults, ≥65 years, in the Cardiovascular Health Study without HF at baseline, 1505 had hyperuricemia (baseline serum uric acid ≥6 mg/dL for women and ≥7 mg/dL for men). Using propensity scores for hyperuricemia, estimated for each participant using 64 baseline covariates, we were able to match 1181 pairs of participants with and without hyperuricemia.
Results
Incident HF occurred in 21% and 18% of participants respectively with and without hyperuricemia during 8.1 years of mean follow-up (hazard ratio {HR} for hyperuricemia versus no hyperuricemia, 1.30; 95% confidence interval {CI}, 1.05–1.60; P=0.015). The association between hyperuricemia and incident HF was significant only in subgroups with normal kidney function (HR, 1.23; 95% CI, 1.02–1.49; P=0.031), without hypertension (HR, 1.31; 95% CI, 1.03–1.66; P=0.030), not receiving thiazide diuretics (HR, 1.20; 95% CI, 1.01–1.42; P=0.044), and without hyperinsulinemia (HR, 1.35; 95% CI, 1.06–1.72; P=0.013). Used as a continuous variable, each 1 mg/dL increase in serum uric acid was associated with a 12% increase in incident HF (HR, 1.12; 95% CI, 1.03–1.22; P=0.006). Hyperuricemia had no association with acute myocardial infarction or all-cause mortality.
Conclusions
Hyperuricemia is associated with incident HF in community-dwelling older adults. Cumulative data from our subgroup analyses suggest that this association is only significant when hyperuricemia is a marker of increased xanthine oxidase activity but not when hyperuricemia is caused by impaired renal elimination of uric acid.
doi:10.1016/j.ijcard.2009.01.010
PMCID: PMC2906633
PMID: 19201041
Uric acid; incident heart failure; kidney function; propensity score
Background
National guidelines for primary prevention suggest consideration of lifetime risk for cardiovascular disease in addition to 10-year risk, but it is currently unknown how many U.S. adults would be identified as having low short-term but high lifetime predicted risk if stepwise stratification were employed.
Methods and Results
We included 6,329 CVD-free and nonpregnant individuals aged 20 to 79 years, representing approximately 156 million U.S. adults, from the National Health and Nutrition Examination Survey 2003–2004 and 2005–2006. We assigned 10-year and lifetime predicted risks to stratify participants into three groups: low 10-year (<10%)/low lifetime (<39%) predicted risk, low 10-year (<10%)/high lifetime (≥39%) predicted risk, and high 10-year (≥10%) predicted risk or diagnosed diabetes. The majority of U.S. adults (56%, or 87 million individuals) are at low short-term but high lifetime predicted risk for cardiovascular disease. Twenty-six percent (41 million adults) are at low short-term and low lifetime predicted risk, and only 18% (28 million individuals) are at high short-term predicted risk. The addition of lifetime risk estimation to 10-year risk estimation identifies higher risk women and younger men in particular.
Conclusions
Whereas 82% of U.S. adults are at low short-term risk, two-thirds of this group, or 87 million people, are at high lifetime predicted risk for cardiovascular disease. These results provide support for use of a stepwise stratification system aimed at improving risk communication, and they provide a baseline for public health efforts aimed at increasing the proportion of Americans with low short-term and low lifetime risk for cardiovascular disease.
doi:10.1161/CIRCOUTCOMES.109.869727
PMCID: PMC3058791
PMID: 20123666
Berry, Jarett D. | Prineas, Ronald J. | van Horn, Linda | Passman, Rod | Larson, Joseph | Goldberger, Jeffrey | Snetselaar, Linda | Tinker, Lesley | Liu, Kiang | Lloyd-Jones, Donald M.
Experimental and clinical trial data suggest an association between fish oil intake and atrial fibrillation (AF). However, prior observational studies have reported conflicting results regarding this association. Thus, we sought to compare the association between dietary fish intake and incident AF in a large sample of older, postmenopausal women. We included 44,720 participants from the Women's Health Initiative clinical trials not enrolled in the dietary modification intervention arm and without AF at baseline. The dietary intake of non-fried fish and omega-3 fatty acid intake were estimated from a Food Frequency Questionnaire at study entry. Incident AF was determined by follow-up ECG at year 3 and year 6. Baseline characteristics and rates of incident AF were compared across quartiles (Q) of fish intake. Adjusted logistic regression models were used to evaluate the association between dietary non-fried fish intake and incident AF. There were 378 incident cases of AF in follow-up. In age-adjusted models, there was no association between dietary non-fried fish intake and incident AF [odds ratios (95% confidence intervals) 1.17 (0.88–1.57) for Q 4 vs. Q 1 of dietary fish intake). Similar findings were observed in multivariable models and in subgroup analyses. In a large cohort of healthy women, we found no evidence of an association between fish or omega-3 fatty acid intake and incident AF.
doi:10.1016/j.amjcard.2009.11.039
PMCID: PMC2838232
PMID: 20211329
atrial fibrillation; diet; omega-3 fatty acids
Background
Long-term blood pressure (BP) progression and its importance as a predictor of clinical outcome have not been well characterized across different time periods.
Methods
We evaluated time-period trends for three BP variables (long-term slope and mean during a baseline period of 16 years, and last baseline value) in an earlier (1953–1971; n=1644, mean age 61 years) and later (1971–1990; n=1040, mean age 58 years) time period among initially non-hypertensive participants in the Framingham Heart Study. In addition, we explored the relations of BP to cardiovascular disease incidence and all-cause mortality in the two time periods, each with up to 16 years of follow up.
Results
Long-term slope, mean, and last baseline BPs were significantly lower in the later time period (P<0.001). Rates of hypertension control (BP<140/90 mm Hg) were higher in the later vs. earlier period (32% vs. 23%; P<0.001). Multivariable hazard ratios (HR) for the relations of BP to outcomes were generally lower in the later period; this was statistically significant for the relations of last baseline BP to all-cause mortality (HR for 1-SD-increase in systolic BP, 1.02 vs. 1.25, P=0.032; HR for diastolic BP 1.00 vs. 1.23, P=0.036).
Conclusions
We found evidence that BP levels in the community have changed over time, coinciding with improved rates of hypertension control and attenuation of BP-mortality relations. These findings are consistent with the hypothesis that hypertension treatment in the community has altered the natural history of BP progression and its relation to clinical outcome.
doi:10.1001/archinte.168.13.1450
PMCID: PMC3023922
PMID: 18625926
Ahmed, Ali | Aban, Inmaculada B | Vaccarino, Viola | Lloyd‐Jones, Donald M | Goff, David C | Zhao, Jiannan | Love, Thomas E | Ritchie, Christine | Ovalle, Fernando | Gambassi, Giovanni | Dell'Italia, Louis J
Heart
2007;93(12):1584-1590.
Background
Poor prognosis in heart failure (HF) patients with diabetes is often attributed to increased co‐morbidity and advanced disease. Further, this effect may be worse in women.
Objective
To determine whether the effect of diabetes on outcomes and the sex‐related variation persisted in a propensity score‐matched HF population, and whether the sex‐related variation was a function of age.
Methods
Of the 7788 HF patients in the Digitalis Investigation Group trial, 2218 had a history of diabetes. Propensity score for diabetes was calculated for each patient using a non‐parsimonious logistic regression model incorporating all measured baseline covariates, and was used to match 2056 (93%) diabetic patients with 2056 non‐diabetic patients.
Results
All‐cause mortality occurred in 135 (25%) and 216 (39%) women without and with diabetes (adjusted HR = 1.67; 95% CI = 1.34 to 2.08; p<0.001). Among men, 535 (36%) and 609 (41%) patients without and with diabetes died from all causes (adjusted HR = 1.21; 95% CI = 1.07 to 1.36; p = 0.002). Sex–diabetes interaction (overall adjusted p<0.001) was only significant in patients ⩾65 years (15% absolute risk increase in women; multivariable p for interaction = 0.005), but not in younger patients (2% increase in women; p for interaction = 0.173). Risk‐adjusted HR (95% CI) for all‐cause hospitalisation for women and men were 1.49 (1.28 to 1.72) and 1.21 (1.11 to 1.32), respectively, also with significant sex–diabetes interaction (p = 0.011).
Conclusions
Diabetes‐associated increases in morbidity and mortality in chronic HF were more pronounced in women, and theses sex‐related differences in outcomes were primarily observed in elderly patients.
doi:10.1136/hrt.2006.113522
PMCID: PMC2095739
PMID: 17488764
Lloyd-Jones, Donald M. | Walsh, Joseph A | Prineas, Ronald J. | Ning, Hongyan | Liu, Kiang | Daviglus, Martha L. | Shea, Steven | Detrano, Robert C. | Tandri, Harikrishna | Greenland, Philip
Isolated minor non-specific ST-segment and T-wave (NSSTA), minor and major electrocardiographic (ECG) abnormalities are established, independent risk markers for incident cardiovascular events. Their association with subclinical atherosclerosis has been postulated but is not clearly defined. The aim of this study is to define the association between ECG abnormalities and measures of subclinical atherosclerosis. We studied participants from MESA, a multi-ethnic sample of men and women aged 45–84 and free of clinical cardiovascular disease at enrollment. Baseline examination included measurement of traditional risk factors, resting 12-lead electrocardiograms, coronary artery calcium (CAC) measurement and common carotid intima-media thickness (CCIMT). Electrocardiograms were coded using Novacode criteria and were defined as having either minor abnormalities (e.g., minor non-specific STTA, first degree atrioventricular block, and QRS axis deviations) or major abnormalities (e.g., pathologic Q waves, major ST-segment and T-wave abnormalities, significant dysrhythmias and conduction system delays). Multivariable logistic and linear regressions were used to determine the cross-sectional associations of ECG abnormalities with CAC and common carotid-IMT. Among 6710 participants, 52.7% were women, with a mean age of 62 years. After multivariable-adjustment, isolated minor STTA, minor and major ECG abnormalities were not associated with the presence of CAC (>0) among men (OR 1.04, 95% CI 0.81–1.33; 1.10, 0.91–1.32; and 1.03, 0.81–1.31, respectively) or women (1.01, 0.82–1.24; 1.04, 0.87–1.23; and 0.94, 0.73–1.22, respectively). Lack of association remained consistent when using both log CAC and CC-IMT as continuous variables. ECG abnormalities are not associated with markers of subclinical atherosclerosis in a large multi-ethnic cohort.
doi:10.1016/j.amjcard.2009.05.060
PMCID: PMC2871277
PMID: 19801030