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Data are sparse regarding the actual predictive utility of pulse pressure and other blood pressure measures for cardiovascular events. We included all of the participants from the Chicago Heart Association Detection Project in Industry who were free of cardiovascular disease and not receiving antihypertensive treatment at baseline (1967-1973). Baseline blood pressure measures were assessed for predictive utility for fatal and nonfatal events over 33 years. Among 36 314 participants (mean age: 39+/-13 years; 43.4% women), there were 11 452 deaths: 745 were attributed to stroke, 2812 to coronary disease, and 599 to heart failure. Of the 16 393 participants who attained Medicare eligibility, 3050, 1367, and 2207 had >or=1 hospitalization for stroke, myocardial infarction, or heart failure, respectively. In univariate analyses, hazards ratios for stroke death per SD of pulse, systolic, and diastolic pressure, respectively, were 1.49, 1.75, and 1.71. Likelihood ratio chi(2) (134.3, 302.0, and 232.6, respectively), Bayes information criteria values (15 142, 14 974, and 15 044, respectively), and areas under receiver-operating characteristic curves (0.59, 0.64, and 0.63, respectively) all indicated better predictive utility for systolic and diastolic compared with pulse pressure. Results for coronary or heart failure death and stroke, myocardial infarction, or heart failure hospitalization were similar. Pulse pressure had weaker predictive utility at all ages but particularly for those <50 years. In this large cohort study, pulse pressure had predictive utility for cardiovascular events that was inferior to systolic or diastolic pressure. These findings support the approach of current guidelines in the use of systolic and diastolic blood pressure to assess risk and the need for treatment.

Background: Hospitalization for acute decompensated heart failure (ADHF) is associated with a high postdischarge mortality and readmission rate. The association between baseline blood urea nitrogen (BUN) and clinical outcomes in patients admitted for ADHF was evaluated in a post-hoc analysis of the ACTIV in CHF trial., Methods and Results: Patients were categorized into quartiles according to baseline BUN. Cox proportional hazards regression was used to test the association between BUN, mortality, and death or readmission within 60 days. Patients in the highest quartile (>40 mg/dL) had the highest 60-day mortality (14.3%, 9.3%, 4.0%, 0%, respectively; P < .001) and the highest rate of death or heart failure hospitalization (30.0%, 21.3% 18.4%, 8.6%; P < .001). After adjustment for covariates, BUN was a statistically significant predictor of both mortality and the composite endpoint of death or heart failure hospitalization at 60 days after hospital discharge. Serum creatinine and estimated creatinine clearance did not predict mortality after covariate adjustment., Conclusions: Higher baseline BUN is a powerful predictor of increased postdischarge mortality in patients hospitalized for heart failure, even in the absence of severe renal failure. Even mild to moderate elevations in baseline BUN were predictive. BUN remains an easily accessible risk stratification tool that physicians should closely monitor in the hospital setting.

Background: Patients with end-stage renal disease (ESRD) have a high incidence of sudden cardiac death and may benefit from implantable cardioverter defibrillators (ICDs). However, ESRD also may predispose patients to device-related complications, potentially offsetting some of the benefits of prophylactic ICD placement. The purpose of this study is to compare the incidence of complications after cardiac rhythm management device (CRMD) implantation in patients with and without ESRD., Methods: An observational study was performed on 41 patients with ESRD and 123 controls without ESRD who had a CRMD (permanent pacemaker or ICD) implanted at a single institution from 1998 to 2005. Controls were matched for age, sex, type of device, and calendar year of device implantation. Primary and secondary end points were any complication and complications requiring intervention, respectively., Results: 23 complications occurred in 16 of 41 patients with ESRD (39%) versus 13 complications in 13 of 123 matched controls (11%; P < 0.001). Major complications occurred in 29% of patients with ESRD versus 5% of controls (P < 0.001), whereas minor complications occurred in 17% and 6%, respectively (P < 0.03). Hematoma, thrombosis, and device-related complications, including elevated defibrillation thresholds, were more common in patients with ESRD (P < 0.05 for all), and there also was a nonsignificant trend toward greater infection risk (P = 0.1). There were no fatal complications in either group., Conclusions: Patients with ESRD had greater complication rates after CRMD implantation compared with matched controls, but these complications did not result in death. These results should be considered when evaluating patients with ESRD for prophylactic CRMD implantation, but do not support withholding such therapy.

The purpose of the study is to examine the prevalence and significance of minor nonspecific ST-segment and T-wave abnormalities (NSSTTA) in the prediction of future cardiovascular disease (CVD) events. Minor NSSTTA are commonly encountered in clinical practice. To date, there have been no systematic reviews focusing on the prevalence and prognostic importance of these findings. Literature searches of MEDLINE (1966-2005) were supplemented with searches of bibliographies from key articles. We focused on isolated minor NSSTTA in healthy middle-aged or elderly populations, including men, women, blacks, and whites, and the association of isolated minor NSSTTA with incident cardiovascular and coronary events. Isolated minor NSSTTA are common in middle-aged white men (ranging from 3.6% to 10.3%), and seem to be even more prevalent in women, blacks, and the elderly. In the 3 studies that examined isolated minor NSSTTA, the multivariable-adjusted hazard ratios for coronary mortality ranged from 1.24 to 1.66. Although gender, race, and age-specific differences in the prognostic significance of minor NSSTTA are not clear because of limited data, minor NSSTTA in asymptomatic patients are an important risk factor for coronary and cardiovascular mortality, independent of traditional risk factors. Minor NSSTTA are prevalent in asymptomatic individuals, and they confer increased risk for CVD and coronary heart disease (CHD), independent of traditional risk factors. Future studies with standardized methodology are needed to elucidate the physiological significance of minor NSSTTA and to further describe gender, race, and age-related differences in the prevalence and prognostic significance of minor NSSTTA.

Context: Data are sparse regarding the prevalence, incidence, and independent prognostic value of minor and/or major electrocardiographic (ECG) abnormalities in asymptomatic postmenopausal women. There is no information on the effect, if any, of hormonal treatment on the prognostic value of the ECG., Objective: To examine association of minor and major baseline and incident ECG abnormalities with long-term cardiovascular morbidity and mortality., Design, Setting, and Participants: Post-hoc analysis of the estrogen plus progestin component of the Women's Health Initiative study, a randomized controlled primary prevention trial of 14 749 postmenopausal asymptomatic women with intact uterus who received 1 daily tablet containing 0.625 mg of oral conjugated equine estrogen and 2.5 mg of medroxyprogesterone acetate or a matching placebo. Participants were enrolled from 1993 to 1998, and the estrogen plus progestin trial was stopped on July 7, 2002., Main Outcome Measures: The Novacode criteria were used to define minor, major, and incident ECG abnormalities. Cardiovascular end points included incident coronary heart disease (CHD) and cardiovascular disease (CVD) events., Results: Among women with absent (n = 9744), minor (n = 4095), and major (n = 910) ECG abnormalities, there were 118, 91, and 37 incident CHD events, respectively. The incident annual CHD event rates per 10 000 women with absent, minor, or major ECG abnormalities were 21 (95% confidence interval [CI], 18-26), 40 (95% CI, 32-49), and 75 (95% CI, 54-104), respectively. After 3 years of follow-up, 5% of women who had normal ECG at baseline developed new ECG abnormalities with an annual CHD event rate of 85 (95% CI, 44-164) per 10 000 women. The adjusted hazard ratios for CHD events were 1.55 (95% CI, 1.14-2.11) for minor baseline, 3.01 (95% CI, 2.03-4.46) for major baseline, and 2.60 (95% CI, 1.08-6.27) for incident ECG abnormalities. There were no significant interactions between hormone treatment assignment and ECG abnormalities for risk prediction of cardiovascular end points. For prediction of CHD events, the addition of ECG findings to the Framingham risk score increased from 0.69 to 0.74 the area under the receiver operating characteristic curve. Similar findings were found for incident CVD events., Conclusions: Among asymptomatic postmenopausal women, clinically relevant baseline and incident ECG abnormalities are independently associated with increased risk of cardiovascular events and mortality, and the information is incremental to the established method of risk stratification., Trial Registration: clinicaltrials.gov Identifier: NCT00000611.

Background: Data are sparse regarding the association of stable body mass index (BMI) over the long term with metabolic syndrome components in young adults., Methods and Results: Participants in the Coronary Artery Risk Development in Young Adults Study, including white and black adults 18 to 30 years of age at the initial examination in 1985 to 1986, were stratified into groups by baseline BMI and change in BMI (stable/decreased, increased >2 kg/m2, or fluctuating) across all 6 examinations between years 0 and 15 of the study. Changes in metabolic syndrome components were compared between groups. Among 1358 men and 1321 women, 16.3% maintained a stable BMI, 73.9% had an increased BMI, and 9.8% had a fluctuating BMI. Over 15 years, participants with stable BMI had essentially unchanged levels of metabolic syndrome components, regardless of baseline BMI, whereas those with increased BMI had progressively worsening levels. For example, men with a baseline BMI of 20.0 to 24.9 kg/m2 and stable BMI during follow-up had a mean increase of only 15 mg/dL in fasting triglycerides over 15 years compared with 65 mg/dL (P<0.001) in those whose BMI increased. Incidence of metabolic syndrome at year 15 was lower in the stable BMI group (2.2%) compared with the increased BMI group (18.8%; P<0.001)., Conclusions: Adverse progression of metabolic syndrome components with advancing age may not be inevitable. Young adults who maintained stable BMI over time had minimal progression of risk factors and lower incidence of metabolic syndrome regardless of baseline BMI. Greater public health efforts should be aimed at long-term weight stabilization.

Background: Amino (N)-terminal pro-brain natriuretic peptide (NT-proBNP) testing is useful for diagnostic and prognostic evaluation in patients with dyspnea. An inverse relationship between body mass index (BMI); (calculated as weight in kilograms divided by height in meters squared) and NT-proBNP concentrations has been described., Methods: One thousand one hundred three patients presenting to the emergency department with acute dyspnea underwent analysis. Patients were classified into the following 3 BMI categories: lean (<25.0), overweight (25.0-29.9), and obese (>/=30.0)., Results: The NT-proBNP concentrations in the overweight and obese groups were significantly lower than in the lean patients, regardless of the presence of acute heart failure (P<.001). The positive likelihood ratio for an NT-proBNP-based diagnosis of acute heart failure was 5.3 for a BMI lower than 25.0, 13.3 for a BMI of 25.0 to 29.9, and 7.5 for a BMI of 30.0 or higher. A cut point of 300 ng/L had very low negative likelihood ratios in all 3 BMI categories (0.02, 0.03, and 0.08, respectively). Among decedents, the NT-proBNP concentrations were lower in the overweight and obese patients compared with the lean subjects (P<.001). Nonetheless, a single cut point of 986 ng/L strongly predicted 1-year mortality across the 3 BMI strata, regardless of the presence of acute heart failure (hazard ratios, 2.22, 3.06, and 3.69 for BMIs of <25.0, 25.0-29.9, and >/=30.0, respectively; all P<.004); the risk associated with a high NT-proBNP concentration was detected early and was sustained to a year after baseline in all 3 BMI strata (all P<.001)., Conclusions: In patients with and without acute heart failure, the NT-proBNP concentrations are relatively lower in overweight and obese patients with acute dyspnea. Despite this, the NT-proBNP concentration retains its diagnostic and prognostic capacity across all BMI categories.

Few data exist regarding the association of risk factor burden in middle age with lifetime risks for cardiovascular disease (CVD) and non-CVD death. In this study, participants in the Chicago Heart Association Detection Project in Industry aged 40 to 59 years in 1967 to 1973 were stratified into 5 groups on the basis of risk factor burden: favorable risk factor profile (untreated blood pressure or=1 unfavorable; or any 1, any 2, or >or=3 elevated (systolic >or=140 mm Hg or diastolic >or=90 mm Hg or treated hypertension; total cholesterol >or=240 mg/dl; current smoking; or body mass index >or=30 kg/m2). Remaining lifetime risks for CVD and non-CVD death were estimated through the age of 85 years. Eight thousand thirty-three men and 6,493 women were followed for 409,987 person-years; 2,582 died of CVD, and 3,955 died of non-CVD causes. A greater risk factor burden was associated with a higher incidence of CVD and non-CVD death. Compared with participants with >or=3 risk factors, those with favorable profiles had substantially lower lifetime risks for CVD death (20.5% vs 35.2% in men, 6.7% vs 31.9% in women) and markedly longer median Kaplan-Meier survival (>35 vs 26 years in men, >35 vs 28 years in women). In conclusion, having favorable risk factors in middle age is associated with a lower lifetime risk for CVD death and markedly longer survival. These results should encourage efforts aimed at preventing the development of risk factors in younger subjects to decrease CVD mortality and promote longevity.

We tested whether slower heart rate recovery (HRR) following graded exercise treadmill testing (GXT) was associated with the presence of coronary artery calcium (CAC). Participants (n = 2,648) ages 18-30 years at baseline examination underwent GXT, followed by CAC screening 15 years later. Slow HRR was not associated with higher odds of testing positive (yes/no) for CAC at year 15 (OR = 0.99, p = 0.91 per standard deviation change in HRR). Slow HRR in young adulthood is not associated with the presence of CAC at middle age.

Background: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing is useful for diagnosis or exclusion of heart failure (HF) in dyspneic patients. Atrial fibrillation (AF) may cause dyspnea in the absence of acute HF and may also affect plasma levels of NT-proBNP., Methods: We prospectively enrolled 599 patients presenting with dyspnea to the emergency department and obtained a blood sample for NT-proBNP measurement. The diagnosis of AF was identified via presentation electrocardiogram. A final diagnosis of HF was determined by blinded study physicians using all available hospital records for each subject through 60 days of follow-up. We assessed the association between the presence of AF and level of NT-proBNP in subsets of patients with and without HF., Results: Of 599 dyspneic patients, 75 (13%) were in AF at presentation; these patients had significantly higher median NT-proBNP levels when compared with those without AF (2934 vs 294 pg/mL, P < .0001). Among patients with acute HF, AF was present in 28%; NT-proBNP levels were lower in those with AF versus those without (3488 vs 4492 pg/mL, P < .001), but AF was not independently associated with NT-proBNP after multivariable adjustment. In patients without acute HF, median NT-proBNP concentrations were significantly higher in those with AF than in those without (932 vs 121 pg/mL, P = .02); in these subjects, AF was the strongest predictor of an NT-proBNP concentration in a range consistent with acute HF (odds ratio 9.94, 95% CI 2.97-33.3, P < .001)., Conclusion: Atrial fibrillation is associated with higher NT-proBNP concentrations in dyspneic patients, particularly in those without acute HF.

Purpose of Review: The aim of this article is to describe recent advances in our understanding of lifetime risks for cardiovascular disease and their implications for lipid guidelines., Recent Findings: Recent studies have indicated that, among younger and middle-aged adults, there is a large subset with low 10-year risk but high lifetime risk for cardiovascular disease. Individuals with high lifetime risks can be identified on the basis of single adverse risk factors or on the basis of overall risk factor burden. For example, using the ATP-III online risk estimator, a 45-year-old obese, nonsmoking, nondiabetic man with total cholesterol of 200 mg/dl, HDL-cholesterol of 40 mg/dl, and untreated systolic blood pressure of 135 mmHg has an estimated 10-year risk for hard coronary heart disease of 3%. In contrast, recent data indicate that his predicted remaining lifetime risk for cardiovascular disease is 50% and his predicted median survival is over 10 years shorter than a man at the same age with optimal risk factors., Summary: Lifetime risk estimation for cardiovascular disease may be an important adjunct to short-term (10-year) risk estimation that may help identify more treatment-eligible individuals at risk for cardiovascular disease, improve risk communication, motivate changes in lifestyle and behaviors, and promote adherence to therapy.

Background: The National Cholesterol Education Program Adult Treatment Panel report from 2001 (ATP III) recommends clinicians calculate 10-year coronary risk using multivariable methods only for adults with 2 or more risk factors. We aimed to determine who would be falsely classified as low risk using this approach., Methods: We studied 4097 adults aged 20 to 79 years without diagnosed cardiovascular disease or diabetes from the National Health and Nutrition Examination Survey from 1999 to 2002. We determined the proportion with fewer than 2 risk factors who nonetheless had estimated 10-year risk of cardiac death or myocardial infarction > or =10% using multivariable methods., Results: Among persons with fewer than 2 risk factors, 5.3% (95% confidence interval 4.7 to 6.1%), had a 10-year risk > or =10% using the Framingham Risk Score and would be misclassified using the risk factor counting method (this corresponds to approximately 5,640,000 U.S. adults). Compared to individuals whose classification was unchanged, those misclassified as low risk were older (P<0.001) and more likely male (85.5% vs. 41.2%, P<0.001)., Conclusions: Relying on the ATP III risk factor counting method rather than determining risk using multivariable methods in all patients resulted in misclassifiying as low risk over 5 million adults with at least moderately high risk of coronary heart disease, most of whom are middle-aged and older men.

Some experts propose C-reactive protein (CRP) as a screening tool for prediction of cardiovascular disease (CVD). Many epidemiologic studies show positive associations between elevated CRP levels and incident CVD. Assessment of the value of new prognostic tests, however, must rely on understanding of test characteristics rather than on associations measured by relative risks. In the case of CRP, test characteristics must be judged in the context of currently available CVD risk prediction algorithms. In this review of literature published before January 2006, the authors describe what is known about the additional utility of CRP in risk prediction. They find no definitive evidence that, for most individuals, CRP adds substantial predictive value above that provided by risk estimation using traditional risk factors for CVD. Use of CRP may add to risk estimation in a limited subset of individuals who are at intermediate predicted risk according to the Framingham risk score. The authors propose that many questions still must be addressed before CRP is incorporated into risk prediction algorithms and before universal screening with CRP can be recommended.

Two cases of patients presenting with opioid dependence who maintained their dependence with poppy tea are described. There appears to have been an increase in this practice in some groups, although dependent use is uncommon. These cases illustrate significant levels of dependence on a licit, and readily available, source of opiates requiring high doses of pharmacotherapy that match those typically required by individuals who are treated for heroin dependence.

Background: Recent attention to racial and ethnic disparities in health outcomes highlights the excess coronary heart disease mortality in black patients compared with white patients. We investigated whether traditional cardiovascular disease (CVD) risk factors were similarly associated with CVD mortality in black and white men and women., Methods: Participants included 3741 black and 33,246 white men and women (44%) without a history of myocardial infarction, aged 18 to 64 years at baseline (1967-1973) from the Chicago Heart Association Detection Project in Industry study. Blood pressure, total cholesterol level, body mass index, cigarette smoking, and physician-diagnosed diabetes were assessed at baseline using standard methods., Results: Through 2002, there were 107, 1586, 177, and 2866 deaths from CVD in black women, white women, black men, and white men, respectively. In general, the magnitude and direction of associations between traditional risk factors and CVD mortality were similar by race. However, in black women the multivariable-adjusted hazard ratio (HR) per 12 mm Hg of diastolic blood pressure was 1.08 (95% confidence interval [CI], 0.90-1.29), whereas it was 1.31 in white women (95% CI, 1.25-1.38). There was no association between higher cholesterol level (per 40 mg/dL [1.04 mmol/L]) and CVD mortality in black men (HR, 0.94; 95% CI, 0.80-1.10), whereas the risk was elevated in white men (HR, 1.21; 95% CI, 1.16-1.26)., Conclusions: Most traditional risk factors demonstrated similar associations with mortality in black and white adults of the same sex. Small differences were primarily in the strength, not the direction, of association.

Background: Data are sparse regarding comparative long-term mortality across the spectrum of patients presenting with acute coronary syndrome (ACS)., Methods: We identified all patients hospitalized with suspected myocardial ischemia in an urban academic hospital from 1991 to 1992. We compared presenting characteristics, treatment, and long-term mortality between patients with unstable angina (UA), minor myocardial damage (MMD), definite non-ST-elevation myocardial infarction (NSTEMI), and STEMI., Results: Of 760 patients (mean age 68 years, 35% women), 22% had UA, 35% had MMD, 26% had NSTEMI, and 17% had STEMI. During a mean follow-up of 9.5 years, unadjusted mortality was highest in patients with MMD and NSTEMI (mortality for UA 43%, MMD 68%, NSTEMI 62%, STEMI 44%; P < .001). Patients with MMD and NSTEMI were older than patients with STEMI or UA, had more comorbid conditions (diabetes, prior myocardial infarction, congestive heart failure), and were less likely to receive aspirin, unfractionated heparin, or revascularization therapies during the index hospitalization. After multivariable adjustment for all significant covariates, mortality increased sequentially along the spectrum of ACS (hazards ratios for UA 1.0 [referent], MMD 1.12 [95% CI 0.84-1.49], NSTEMI 1.28 [0.95-1.72], and STEMI 1.52 [1.06-2.19])., Conclusions: Patients presenting with MMD and definite NSTEMI had a worse unadjusted long-term prognosis up to 10 years after index hospitalization than patients with STEMI. This mortality excess for MMD/NSTEMI was associated with more comorbid conditions and decreased use of basic therapies for ACS. After controlling for baseline differences, STEMI patients had the highest mortality.

Background: Lifetime risk for atherosclerotic cardiovascular disease (CVD) has not previously been estimated, and the effect of risk factor burden on lifetime risk is unknown., Methods and Results: We included all Framingham Heart Study participants who were free of CVD (myocardial infarction, coronary insufficiency, angina, stroke, claudication) at 50 years of age. Lifetime risks to 95 years of age were estimated for men and women, with death free of CVD as a competing event. We followed up 3564 men and 4362 women for 111,777 person-years; 1757 had CVD events and 1641 died free of CVD. At 50 years of age, lifetime risks were 51.7% (95% CI, 49.3 to 54.2) for men and 39.2% (95% CI, 37.0 to 41.4) for women, with median survivals of 30 and 36 years, respectively. With more adverse levels of single risk factors, lifetime risks increased and median survivals decreased. Compared with participants with > or =2 major risk factors, those with optimal levels had substantially lower lifetime risks (5.2% versus 68.9% in men, 8.2% versus 50.2% in women) and markedly longer median survivals (>39 versus 28 years in men, >39 versus 31 years in women)., Conclusions: The absence of established risk factors at 50 years of age is associated with very low lifetime risk for CVD and markedly longer survival. These results should promote efforts aimed at preventing development of risk factors in young individuals. Given the high lifetime risks and lower survival in those with intermediate or high risk factor burden at 50 years of age, these data may be useful in communicating risks and supporting intensive preventive therapy.

Background: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful for diagnosis and triage of patients with dyspnea, but its role for predicting outcomes in such patients remains undefined., Methods: A total of 599 breathless patients treated in the emergency department were prospectively enrolled, and a sample of blood was obtained for NT-proBNP measurements. After 1 year, the vital status of each patient was ascertained, and the association between NT-proBNP values at presentation and mortality was assessed., Results: At 1 year, 91 patients (15.2%) had died. Median NT-proBNP concentrations at presentation among decedents were significantly higher than those of survivors (3277 vs 299 pg/mL; P<.001). The optimal NT-proBNP cut point for predicting 1-year mortality was 986 pg/mL. In a multivariable model, an NT-proBNP concentration greater than 986 pg/mL at presentation was the single strongest predictor of death at 1 year (hazard ratio [HR], 2.88; 95% confidence interval, 1.64-5.06; P<.001), independent of a diagnosis of heart failure. Other factors associated with death included age (by decade; HR, 1.20), heart rate (by decile; HR, 1.13), urea nitrogen level (by decile; HR, 1.20), systolic blood pressure less than 100 mm Hg (HR, 1.94), heart murmur (HR, 1.92), and New York Heart Association classification (HR, 1.38 for each increase in class). The NT-proBNP concentration alone had an area under the receiver operating characteristic curve (AUC) of 0.76 for predicting mortality; the other significant covariates combined had an AUC of 0.80. The final model for predicting death, combining NT-proBNP with other covariates associated with mortality, had a superior AUC of 0.82., Conclusion: In addition to assisting in emergency department diagnosis and triage, NT-proBNP concentrations at presentation are strongly predictive of 1-year mortality in dyspneic patients.

Background: Modifications to the National Cholesterol Education Program (NCEP) guidelines lowered optional low-density lipoprotein cholesterol (LDL-C) treatment goals., Objective: We evaluated the implications of widely adopting these optional goals in clinical practice., Design and Participants: We performed a cross-sectional study using 1999 to 2002 data from 3,281 U.S. adults aged 20 to 79 years participating the National Health and Nutrition Examination Survey., Measurements: The primary outcomes were the proportions of adults whose fasting LDL-C levels exceeded NCEP recommended and optional targets from 2001 and 2004. We used survey weights to estimate the size of the U.S. population exceeding targets. We examined outcomes for 4 coronary disease risk subgroups described by the NCEP., Results: Low-density lipoprotein cholesterol values exceeded 2001 NCEP goals for 30.0% of adults, and 35.8% had levels above optional 2004 goals. An estimated 24,900,000 individuals (14.2%) exceeded 2001 thresholds for drug therapy, 46,200,000 (26.3%) exceeded optional 2001 thresholds for drug therapy, and 56,500,000 (32.2%) were above the optional 2004 thresholds for drug therapy. For lower, moderate, moderately high, and high-risk groups, 13.4%, 44.2%, 58.8%, and 71.8%, respectively, exceeded 2001 NCEP goals; 13.4%, 15.7%, 87.4%, and 96.0% of these groups exceeded optional 2004 thresholds for drug therapy., Conclusions: In 1999 to 2002, LDL-C levels commonly exceeded 2001 NCEP goals, especially for moderately high and high-risk individuals, and cholesterol-lowering medications were underused. Optional goals promulgated by the NCEP in 2001 and 2004 moderately increased the number of adults with LDL-C above their goal, and greatly increased the number of low, moderately high, and high-risk adults who exceeded LDL-C thresholds, for cholesterol-lowering medication.

Unlabelled: The relationship between renal insufficiency and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels remains unclear. We examined this relationship in the context of patients who presented to the emergency department of an urban tertiary care medical center with dyspnea. Even in the presence of renal insufficiency, NT-proBNP remained a valuable tool for the diagnosis of acute congestive heart failure and it provides important prognostic information., Objectives: We sought to examine the interaction between renal function and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels., Background: The effects of renal insufficiency on NT-proBNP among patients with and without acute congestive heart failure (CHF) are controversial. We examined the effects of kidney disease on NT-proBNP-based CHF diagnosis and prognosis., Methods: A total of 599 dyspneic patients with glomerular filtration rates (GFRs) as low as 14.8 ml/min were analyzed. We used multivariate logistic regression to examine covariates associated with NT-proBNP results and linear regression analysis to analyze associations between NT-proBNP and GFR. Receiver-operating characteristic analysis determined the sensitivity and specificity of NT-proBNP for CHF diagnosis. We also assessed 60-day mortality rates as a function of NT-proBNP concentration., Results: Glomerular filtration rates ranged from 15 ml/min/1.73 m2 to 252 ml/min/1.73 m2. Renal insufficiency was associated with risk factors for CHF, and patients with renal insufficiency were more likely to have CHF (all p < 0.003). Worse renal function was accompanied by cardiac structural and functional abnormalities on echocardiography. We found that NT-proBNP and GFR were inversely and independently related (p < 0.001) and that NT-proBNP values of > 450 pg/ml for patients ages <50 years and >900 pg/ml for patients > or =50 years had a sensitivity of 85% and a specificity of 88% for diagnosing acute CHF among subjects with GFR > or =60 ml/min/1.73 m2. Using a cut point of 1,200 pg/ml for subjects with GFR <60 ml/min/1.73 m2, we found sensitivity and specificity to be 89% and 72%, respectively. We found that NT-proBNP was the strongest overall independent risk factor for 60-day mortality (hazard ratio 1.57; 95% confidence interval 1.2 to 2.0; p = 0.0004) and remained so even in those with GFR <60 ml/min/1.73 m2 (hazard ratio 1.61; 95% confidence interval 1.14 to 2.26; p = 0.006)., Conclusions: The use of NT-proBNP testing is valuable for the evaluation of the dyspneic patient with suspected CHF, irrespective of renal function.

Cardiovascular disease (CVD), particularly coronary heart disease (CHD), remains a major cause of mortality, morbidity, and disability in the US and other Westernized societies. As a result of therapeutic and preventive measures to control the CVD/CHD epidemic, mortality has declined steadily during the last several decades with a consequent gain in life expectancy, but the 1990s witnessed a slowing of this decline. In response to these trends, a range of therapeutic regimens were developed to address adverse CVD risk factor levels and their deleterious effects. The scientific evidence regarding the efficacy, cost effectiveness, strengths, and limitations of a range of pharmacologic and lifestyle approaches to CVD prevention--both primary and secondary--are reviewed in depth. Clinical trials aimed at primary and secondary prevention of CVD have documented the efficacy and cost effectiveness of various drugs in lowering individual risk factor levels and in reducing clinical CVD events. More recently, the idea of a 'polypill' containing low doses of multiple drugs has generated much interest, with proponents arguing that, given the high prevalence of CVD risk factors and the effectiveness of pharmacologic interventions, such a drug combination would reduce CHD mortality by 88% if taken by all individuals aged > or = 55 years. However, current treatments to control high BP and serum cholesterol, while effective, do not typically reduce morbidity and mortality to levels observed in low-risk individuals, i.e. those with favorable levels of all readily measured major risk factors. Rather, primary prevention of all major risk factors starting early in life is critical. Prospective population-based research has delineated multiple long-term benefits associated with low-risk status in young adulthood and middle age, i.e. markedly lower age-specific CVD and total mortality rates, increased life expectancy, lower healthcare costs, lower medication use and prevalence of chronic diseases, and higher self-reported quality of life at older ages. Unfortunately, despite declines in the prevalence of most major CVD risk factors, low-risk status remains rare among US adults. Data have also demonstrated that adverse levels of one or more major risk factors precede clinical CHD in 90% or more of all cases, undermining the assertion that major CVD risk factors account for 'no more than 50%' of CHD cases. Hence, while numerous treatment options exist for secondary prevention of CVD, strategies that focus on progressively increasing the proportion of low-risk individuals could greatly reduce the need for secondary prevention in the first place. Public health policies must focus on prevention of all major risk factors simultaneously, using lifestyle approaches from early ages onwards to reduce population CVD risk to endemic levels, rather than current epidemic levels.

Aims: To determine the effects of digoxin on all-cause mortality and heart failure (HF) hospitalizations, regardless of ejection fraction, accounting for serum digoxin concentration (SDC)., Methods and Results: This comprehensive post-hoc analysis of the randomized controlled Digitalis Investigation Group trial (n=7788) focuses on 5548 patients: 1687 with SDC, drawn randomly at 1 month, and 3861 placebo patients, alive at 1 month. Overall, 33% died and 31% had HF hospitalizations during a 40-month median follow-up. Compared with placebo, SDC 0.5-0.9 ng/mL was associated with lower mortality [29 vs. 33% placebo; adjusted hazard ratio (AHR), 0.77; 95% confidence interval (CI), 0.67-0.89], all-cause hospitalizations (64 vs. 67% placebo; AHR, 0.85; 95% CI, 0.78-0.92) and HF hospitalizations (23 vs. 33% placebo; AHR, 0.62; 95% CI, 0.54-0.72). SDC> or =1.0 ng/mL was associated with lower HF hospitalizations (29 vs. 33% placebo; AHR, 0.68; 95% CI, 0.59-0.79), without any effect on mortality. SDC 0.5-0.9 reduced mortality in a wide spectrum of HF patients and had no interaction with ejection fraction >45% (P=0.834) or sex (P=0.917)., Conclusions: Digoxin at SDC 0.5-0.9 ng/mL reduces mortality and hospitalizations in all HF patients, including those with preserved systolic function. At higher SDC, digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations.

Data are sparse regarding hypertension prevalence, treatment, and control among some ethnic groups of American women. Furthermore, the effects of ethnicity on hypertension, independent of other factors that vary with ethnicity, are poorly understood. We examined the prevalence of hypertension (defined as systolic > or =140 or diastolic > or =90 mm Hg or receiving treatment), treatment, and control (to <140/<90 mm Hg) in a multiethnic study of premenopausal and perimenopausal women. Stepwise multivariable logistic regression was used to select covariates associated with hypertension. Among 3292 women, 46.9% were white, 28.3% were black, 8.7% were Hispanic, 7.6% were Chinese, and 8.5% were Japanese. Among these 5 ethnic groups, respectively, there was substantial variation in prevalence of normal blood pressure levels (<120/<80 mm Hg; 59.9%, 35.4%, 16.8%, 67.2%, and 63.7%) and hypertension (14.5%, 38.1%, 27.6%, 12.8%, and 11.0%). After multivariable adjustment, hypertension prevalence was 2 to 3x higher among black and Hispanic women but similar among Chinese and Japanese women compared with white women. Among hypertensive participants, prevalence of antihypertensive treatment was highest among blacks (58.9%) and whites (55.2%) and lowest among Chinese (34.4%). Prevalence of control to goal blood pressure levels was highest among whites (43.0%) and Japanese (38.7%) and markedly lower among Hispanic women (11.4%). Compared with whites, black and Hispanic women have significantly higher prevalence of hypertension independent of other factors, whereas Chinese and Japanese women have similar prevalence. Treatment and control rates vary considerably across ethnicities. Greater efforts must be made to improve hypertension awareness, treatment, and control in all middle-aged women, particularly those in ethnic minority groups.

In a cohort of 710 patients with acute coronary syndromes (ACSs), we demonstrated that the Thrombolysis In Myocardial Infarction Risk Index--a predictor of 30-day mortality in clinical trial patients with ST-elevation myocardial infarction (STEMI)--is a strong predictor of short- and long-term mortality with good discrimination ability (c statistics 0.77 to 0.79) among all subtypes of ACSs (STEMI, non-STEMI, and unstable angina pectoris). These results verify the utility of the Risk Index in unselected patients with STEMI, broaden its application to other types of ACSs, and extend its utility to stratification of long-term mortality risk.

Context: Data are sparse regarding current rates of hypertension treatment and control, and risks associated with hypertension, among persons older than 80 years., Objective: To determine the prevalence of blood pressure stages, hypertension treatment and control, and cardiovascular risk among older patients with hypertension., Design, Setting, and Participants: A community-based cohort study in which data were collected during all Framingham Heart Study examinations attended in the 1990s. Participants were pooled according to age: younger than 60 years, 60 to 79 years, or 80 years or older. There were 5296 participants who contributed 14 458 person-examinations of observation, including 7135 hypertensive person-examinations (4919 treated)., Main Outcome Measures: Prevalence of hypertension, its treatment, and its control were compared across age groups. Risks for incident cardiovascular disease during follow-up of up to 6 years were estimated as multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression., Results: Prevalence of hypertension and drug treatment increased with advancing age, whereas control rates were markedly lower in older women (systolic <140 and diastolic <90 mm Hg). For ages younger than 60 years, 60 to 79, and 80 years and older, respectively, control rates were 38%, 36%, and 38% in men (P = .30) and 38%, 28%, and 23% in women (P<.001). Relative risks for cardiovascular disease associated with increasing blood pressure stage did not decline with advancing age, and absolute risks increased markedly. Among participants 80 years of age or older, major cardiovascular events occurred in 9.5% of the normal blood pressure (referent) group, 19.8% of the prehypertension group (HR, 1.9; 95% CI, 0.9-3.9), 20.3% of the stage 1 hypertension group (HR, 1.8; 95% CI, 0.8-3.7), and 24.7% of the stage 2 or treated hypertension group (HR, 2.4; 95% CI, 1.2-4.6)., Conclusions: Relative to current national guidelines, rates of blood pressure control in the community are low, especially among older women with hypertension. Short-term risks for cardiovascular disease are substantial, indicating the need for greater efforts at safe, effective risk reduction among the oldest patients with hypertension.

The utility of aminoterminal pro-brain natriuretic peptide (NT-proBNP) testing in the emergency department to rule out acute congestive heart failure (CHF) and the optimal cutpoints for this use are not established. We conducted a prospective study of 600 patients who presented in the emergency department with dyspnea. The clinical diagnosis of acute CHF was determined by study physicians who were blinded to NT-proBNP results. The primary end point was a comparison of NT-proBNP results with the clinical assessment of the managing physician for identifying acute CHF. The median NT-proBNP level among 209 patients (35%) who had acute CHF was 4,054 versus 131 pg/ml among 390 patients (65%) who did not (p <0.001). NT-proBNP at cutpoints of >450 pg/ml for patients <50 years of age and >900 pg/ml for patients >or=50 years of age were highly sensitive and specific for the diagnosis of acute CHF (p <0.001). An NT-proBNP level <300 pg/ml was optimal for ruling out acute CHF, with a negative predictive value of 99%. Increased NT-proBNP was the strongest independent predictor of a final diagnosis of acute CHF (odds ratio 44, 95% confidence interval 21.0 to 91.0, p <0.0001). NT-proBNP testing alone was superior to clinical judgment alone for diagnosing acute CHF (p = 0.006); NT-proBNP plus clinical judgment was superior to NT-proBNP or clinical judgment alone. NT-proBNP measurement is a valuable addition to standard clinical assessment for the identification and exclusion of acute CHF in the emergency department setting.

Background: Lipid lowering with statins prevents adverse cardiac events. Both lipid-lowering and antioxidant therapies may favorably affect vasomotor function and thereby improve ischemia., Methods and Results: In a randomized, double-blind, placebo-controlled trial, 300 patients with stable coronary disease, a positive exercise treadmill test, 48-hour ambulatory ECG with > or =1 episode of ischemia, and fasting total cholesterol of 180 to 250 mg/dL were assigned to 1-year treatment with intensive atorvastatin to reduce LDL to <80 mg/dL (n=96), intensive atorvastatin to reduce LDL to <80 mg/dL plus antioxidant vitamins C (1000 mg/d) and E (800 mg/d) (n=101), or diet and low-dose lovastatin, if needed, to reduce LDL to <130 mg/dL (n=103; control group). Ischemia end points, including ambulatory ECG monitoring and exercise treadmill testing, and endothelial assessment using brachial artery flow-mediated dilation were obtained at baseline and at 6 and 12 months. Baseline characteristics were similar in all groups. LDL decreased from approximately 153 mg/dL at baseline in the 2 atorvastatin groups to approximately 83 mg/dL at 12 months (each P<0.0001) and from 147 to 120 mg/dL in the control group (P<0.0001). During ambulatory ECG monitoring, mean number of ischemic episodes per 48 hours decreased 31% to 61% in each group (each P<0.001; P=0.15 across groups), without a change in daily heart rate activity. Mean duration of ischemia for 48 hours decreased 26% to 62% in each group (each P<0.001; P=0.06 across groups). Mean exercise duration to 1-mm ST-segment depression significantly increased in each group, but total exercise duration and mean sum of maximum ST depression were unchanged. Angina frequency decreased in each group. There was no incremental effect of supplemental vitamins C and E on any ischemia outcome. Flow-mediated dilation studies indicated no meaningful changes., Conclusions: Intensive lipid lowering with atorvastatin to an LDL level of 80 mg/dL, with or without antioxidant vitamins, does not provide any further benefits in ambulatory ischemia, exercise time to onset of ischemia, and angina frequency than moderate lipid lowering with diet and low-dose lovastatin to an LDL level of <120 mg/dL.

The number of deaths due to out-of-hospital coronary heart disease as determined by death certificates was compared with the number physician-adjudicated sudden cardiac deaths in the Framingham Heart Study from 1950 to 1999. Out-of-hospital coronary heart disease deaths overestimated sudden cardiac death by 47%, suggesting that out-of-hospital coronary heart disease death rates derived from death certificates should be interpreted with caution.

Background: Obesity is associated with lower B-type natriuretic peptide (BNP) levels in healthy individuals and patients with chronic congestive heart failure (CHF). Neither the mechanism of natriuretic peptide suppression in the obese patient nor whether obesity affects natriuretic peptide levels among patients with acute CHF is known., Methods: The associations of amino-terminal pro-BNP (NT-proBNP), BNP, and body mass index (BMI) were examined in 204 subjects with acute CHF. Multivariable regression analyses were performed to identify factors independently related to NT-proBNP and BNP levels., Results: Across clinical strata of normal (<25 kg/m2), overweight (25-29.9 kg/m2), and obese (> or =30 kg/m2) patients, median NT-proBNP and BNP levels decreased with increasing BMI (both P values < .001). In multivariable analyses adjusting for covariates known to affect BNP levels, the inverse relationship between BMI and both NT-proBNP and BNP remained ( P < .05 for both). Using a cut point of 900 pg/mL, NT-proBNP was falsely negative in up to 10% of CHF cases in overweight patients (25-29.9 kg/m2) and 15% in obese patients (> or =30 kg/m2). Using the standard cut point of 100 pg/mL, BNP testing was falsely negative in 20% of CHF cases in both overweight and obese patients. The assays for NT-proBNP and BNP exhibited similar overall sensitivity for the diagnosis of CHF., Conclusions: When adjusted for relevant covariates, compared with normal counterparts, overweight and obese patients with acute CHF have lower circulating NT-proBNP and BNP levels, suggesting a BMI-related defect in natriuretic peptide secretion. NT-proBNP fell below the diagnostic cutoff for CHF less often than BNP in overweight and obese individuals; however, when used as a diagnostic tool to identify CHF in such patients, both markers may have reduced sensitivity.

Hypertension confers risk for multiple types of cardiovascular events, but competing risks for these outcomes are unknown. We estimated the competing risks over 12 years after hypertension onset among cases and age-, sex-, and examination-matched controls using competing Cox cumulative incidence and proportional hazards models. We included all Framingham Heart Study subjects examined after 1977 with new-onset hypertension who were free of cardiovascular disease. There were 645 men and 702 women with new-onset hypertension (mean age: men, 55+/-12 years; women, 59+/-12 years). Compared with matched nonhypertensive controls, subjects with new-onset hypertension were more likely to experience a cardiovascular event first rather than noncardiovascular death. Among new-onset hypertensives, the 12-year competing cumulative incidence of any cardiovascular end point as a first event in men was 24.7%, compared with 9.8% for noncardiovascular death (hazards ratio [HR], 2.53; 95% confidence interval [CI], 1.83 to 3.50); in women, the competing incidences were 16.0% versus 10.1%, respectively (HR, 1.58; 95% CI, 1.13 to 2.20). The most common first major cardiovascular events were hard coronary disease (8.2%) in men and stroke (5.2%) in women. Type and incidence of first cardiovascular events varied by age and severity of hypertension at onset, with stroke predominating among older subjects with new-onset hypertension. After hypertension onset, cardiovascular events are more likely to occur first as opposed to noncardiovascular death. Types of initial events differ by gender, age, and severity of hypertension at onset. These results represent a novel approach to understanding the complications of hypertension and may help target therapies for patients with new-onset hypertension to optimize prevention strategies.

Context: For women, impact of cardiovascular risk factors measured in young adulthood, particularly favorable (low-risk) profile, on mortality has been difficult to assess due to low short-term death rates., Objective: To assess the relationship of baseline coronary risk factor status to mortality from coronary heart disease (CHD), cardiovascular diseases (CVDs), and all causes in young women., Design: Prospective cohort study., Setting and Participants: A total of 7302 women aged 18 to 39 years without prior CHD or major electrocardiographic abnormalities screened between 1967 and 1973 for the Chicago Heart Association Detection Project in Industry. Risk groups were defined using national guidelines for values of systolic and diastolic blood pressure, serum cholesterol level, body mass index, presence of diabetes, and smoking status. Participants were divided into 4 groups: low risk, 0 risk factors high but 1 or more unfavorable, 1 only risk factor high, and 2 or more risk factors high., Main Outcome Measures: All-cause mortality, CHD mortality, and CVD mortality; hazard ratio of outcome measures comparing low-risk group with other groups., Results: Only 20% met low-risk criteria; 59% had high levels of 1 or more risk factors. During an average follow-up of 31 years, there were 47 CHD deaths, 94 CVD deaths, and 469 deaths from all causes. The age-adjusted CVD death rate per 10,000 person-years was lowest for low-risk women and increased with the number of risk factors, ie, 1.5, 1.7, 5.0, and 9.1 for low-risk; 0, 1, and 2 or more risk factors high, respectively. Multivariate-adjusted CVD mortality hazard ratio for low-risk women was 0.19 (95% confidence interval, 0.08-0.45) compared with women with 2 or more risk factors high. Similar patterns were observed for CHD and all-cause mortality and for both blacks and whites., Conclusion: For women with favorable levels for all 5 major risk factors at younger ages, CHD and CVD are rare; long-term and all-cause mortality are much lower compared with others.

Background: Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated., Methods and Results: We included all participants in the Framingham Heart Study who were free of AF at index ages of 40 years and older. We estimated lifetime risks for AF (including atrial flutter) to age 95 years, with death free of AF as a competing event. We followed 3999 men and 4726 women from 1968 to 1999 (176 166 person-years); 936 participants had development of AF and 2621 died without prior AF. At age 40 years, lifetime risks for AF were 26.0% (95% CI, 24.0% to 27.0%) for men and 23.0% (21.0% to 24.0%) for women. Lifetime risks did not change substantially with increasing index age despite decreasing remaining years of life because AF incidence rose rapidly with advancing age. At age 80 years, lifetime risks for AF were 22.7% (20.1% to 24.1%) in men and 21.6% (19.3% to 22.7%) in women. In further analyses, counting only those who had development of AF without prior or concurrent congestive heart failure or myocardial infarction, lifetime risks for AF were approximately 16%., Conclusions: Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older. Lifetime risks for AF are high (1 in 6), even in the absence of antecedent congestive heart failure or myocardial infarction. These substantial lifetime risks underscore the major public health burden posed by AF and the need for further investigation into predisposing conditions, preventive strategies, and more effective therapies.

We investigated whether the Framingham risk score, which was designed to estimate the 10-year risk of coronary heart disease (CHD), differentiates lifetime risk for CHD. All subjects in the Framingham Heart Study examined from 1971 to 1996 who were free of CHD were included. Subjects were stratified into age- and gender-specific tertiles of Framingham risk score, and lifetime risk for CHD was estimated. We followed 2,716 men and 3,500 women; 939 developed CHD and 1,363 died free of CHD. At age 40 years, in risk score tertiles 1, 2, and 3, respectively, the lifetime risks for CHD were 38.4%, 41.7%, and 50.7% for men and 12.2%, 25.4%, and 33.2% for women. At age 80 years, risks were 16.4%, 17.4%, and 38.8% for men and 12.8%, 22.4%, and 27.4% for women. The Framingham risk score stratified lifetime risk well for women at all ages. It performed less well in younger men but improved at older ages as remaining life expectancy approached 10 years. Lifetime risks contrasted sharply with shorter term risks: at age 40 years, the 10-year risks of CHD in tertiles 1, 2, and 3, respectively, were 0%, 2.2%, and 11.6% for men and 0%, 0.7%, and 2.3% for women. The Framingham 10-year CHD risk prediction model discriminated short-term risk well for men and women. However, it may not identify subjects with low short-term but high lifetime risk for CHD, likely due to changes in risk factor status over time. Further work is needed to generate multivariate risk models that can reliably predict lifetime risk for CHD.

Context: Atrial fibrillation (AF) is the most common cardiac dysrhythmia in the United States. Whereas rare cases of familial AF have been reported, it is unknown if AF among unselected individuals is a heritable condition., Objective: To determine whether parental AF increases the risk for the development of offspring AF., Design, Setting, and Participants: Prospective cohort study (1983-2002) within the Framingham Heart Study, a population-based epidemiologic study. Participants were 2243 offspring (1165 women, 1078 men) at least 30 years of age and free of AF whose parents had both been evaluated in the original cohort., Main Outcome Measures: Development of new-onset AF in the offspring was prospectively examined in association with previously documented parental AF., Results: Among 2243 offspring participants, 681 (30%) had at least 1 parent with documented AF; 70 offspring participants (23 women; mean age, 62 [range, 40-81] years) developed AF in follow-up. Compared with no parental AF, AF in at least 1 parent increased the risk of offspring AF (multivariable-adjusted odds ratio [OR], 1.85; 95% confidence interval [CI], 1.12-3.06; P =.02). These results were stronger when age was limited to younger than 75 years in both parents and offspring (multivariable-adjusted OR, 3.23; 95% CI, 1.87-5.58; P<.001) and when the sample was further limited to those without antecedent myocardial infarction, heart failure, or valve disease (multivariable-adjusted OR, 3.17; 95% CI, 1.71-5.86; P<.001)., Conclusions: Parental AF increases the future risk for offspring AF, an observation supporting a genetic susceptibility to developing this dysrhythmia. Further research into the genetic factors predisposing to AF is warranted.

Data are sparse regarding the long-term benefit of care concordant with clinical practice guidelines in patients presenting with unstable angina pectoris and non-ST-segment elevation myocardial infarction (UAP/NSTEMI), particularly in the general care setting. We extended follow-up in a preexisting cohort of 275 patients hospitalized with primary UAP/NSTEMI. Using Cox models, we compared long-term mortality between patients who received care concordant with > or =80% of 8 important guideline recommendations during the index hospitalization and patients who did not. Among all study patients, 68% received guideline-concordant care. During follow-up (median 9.4 years) 49% of patients died. Patients with UAP/NSTEMI who received guideline-concordant care had significantly decreased long-term mortality compared with those who received guideline-discordant care (hazards ratio [HR] 0.45, 95% confidence interval [CI] 0.32 to 0.64). Guideline-concordant care remained associated with decreased mortality after adjusting for other predictors of long-term mortality (HR 0.57, 95% CI 0.39 to 0.84) and after adjustment for the propensity to receive guideline-concordant care (HR 0.61, 95% CI 0.43 to 0.88). The benefit of guideline-concordant care relative to discordant care was preserved in high-risk populations shown to be less likely to receive guideline-concordant care, including patients with advanced age, congestive heart failure, elevated serum creatinine, and prior myocardial infarction. Care concordant with UAP/NSTEMI clinical practice guidelines is associated with substantially improved long-term survival. Our findings endorse the approach adopted by authors of clinical practice guidelines in generalizing evidence-based medicine to usual clinical care. In firmly establishing the benefit of consensus guidelines, the foundation is set for efforts to improve practitioner compliance with these standards.

Context: Whether parental cardiovascular disease confers increased risk independent of other risk factors remains controversial. Prior studies relied on offspring report, without complete validation of parental events., Objective: To determine whether parental cardiovascular disease predicts offspring events independent of traditional risk factors, using a prospective design for both parents and offspring, and uniform criteria to validate events., Design: Inception cohort study., Setting: Framingham Heart Study, a US population-based epidemiologic cohort begun in 1948 with the offspring cohort established in 1971., Participants: All Framingham Offspring Study participants (aged > or =30 years) who were free of cardiovascular disease and both parents in the original Framingham cohort., Main Outcome Measures: We examined the association of parental cardiovascular disease with 8-year risk of offspring cardiovascular disease, using pooled logistic regression., Results: Among 2302 men and women (mean age, 44 years), 164 men and 79 women had cardiovascular events during follow-up. Compared with participants with no parental cardiovascular disease, those with at least 1 parent with premature cardiovascular disease (onset age <55 years in father, <65 years in mother) had greater risk for events, with age-adjusted odds ratios of 2.6 (95% confidence interval [CI], 1.7-4.1) for men and 2.3 (95% CI, 1.3-4.3) for women. Multivariable adjustment resulted in odds ratios of 2.0 (95% CI, 1.2-3.1) for men and 1.7 (95% CI, 0.9-3.1) for women. Nonpremature parental cardiovascular disease and parental coronary disease were weaker predictors. Addition of parental information aided in discriminating event rates, notably among offspring with intermediate levels of cholesterol and blood pressure, as well as intermediate predicted multivariable risk., Conclusions: Using validated events, we found that parental cardiovascular disease independently predicted future offspring events in middle-aged adults. Addition of parental information may help clinicians and patients with primary prevention of cardiovascular disease, when treatment decisions may be difficult in patients at intermediate risk based on levels of single or multiple risk factors. These data also support further research into genetic determinants of cardiovascular risk.

Background: Increased low-density lipoprotein (LDL) and oxidized LDL cholesterol levels adversely affect endothelial function in patients with stable coronary artery disease (CAD). Statin drugs are efficacious in primary and secondary prevention of clinical CAD events, but they have not been extensively studied as a treatment for ischemia during routine daily activities or during exercise, indicators of high-risk in patients with stable CAD. The purpose of the Vascular Basis for the Treatment of Myocardial Ischemia study is to determine whether aggressive lowering of LDL cholesterol level with atorvastatin, with or without supplemental antioxidant vitamins C and E, can improve endothelial function and ischemia during ambulatory electrocardiogram (AECG) monitoring and exercise treadmill testing (ETT)., Methods: Patients are eligible when they have ischemia during an ETT and AECG monitoring and when their fasting total cholesterol level is < or =250 mg/dL. Eligible patients are randomized to receive 1 of 3 treatments: intensive atorvastatin to reduce LDL cholesterol level to < or =80 mg/dL, intensive atorvastatin to reduce LDL cholesterol level to < or =80 mg/dL plus antioxidant vitamins C and E, and control of diet and low-dose lovastatin, when needed, to reduce LDL cholesterol level < or = to 130 mg/dL. Patients undergo endothelial function testing, 48-hour AECG monitoring, and ETT at randomization and at 6 and 12 months., Results: A total of 300 patients have been randomized: 101 to receive atorvastatin alone, 103 to receive atorvastatin plus antioxidant vitamins, and 96 to receive placebo. Baseline characteristics are similar across treatment groups., Conclusions: The Vascular Basis study will provide important insight on the effects of aggressive management of dyslipidemia with statin drugs and antioxidant vitamins in patients with stable but high-risk CAD.

Background: Family history is used to infer the risk for heart disease; however, little is known about the accuracy of family history reports., Objective: To examine the accuracy of offspring reports of parental cardiovascular disease., Design: Validation study., Setting: Framingham Heart Study., Participants: Offspring participants of the multigenerational Framingham Heart Study with both parents in the original cohort., Measurements: 791 men and 837 women (mean age, 57 years) completed a family history questionnaire from 1995 to 1998. Offspring reports were compared with confirmed medical evidence of parental status, and positive and negative predictive values and likelihood ratios were calculated., Results: Positive reports of high blood pressure, diabetes, and high cholesterol levels in fathers were accurate: Positive predictive values were 83% (95% CI, 80% to 86%), 76% (CI, 70% to 82%), and 78% (CI, 73% to 83%), respectively. Corresponding positive predictive values for reports in mothers were 91% (CI, 89% to 93%), 79% (CI, 73% to 85%), and 88% (CI, 84% to 92%), respectively. Positive predictive values for reports of paternal heart attack occurring before 55 years of age and for stroke occurring before 65 years of age were 28% (CI, 22% to 34%) and 43% (CI, 33% to 53%), respectively, whereas the positive likelihood ratios were 8.6 (CI, 6.8 to 10.9) and 11.2 (CI, 9.2 to 13.6), respectively. Negative predictive values for parental history reports were greater than 90%, except for high blood pressure and high cholesterol level (negative predictive values, 33% to 55%, and negative likelihood ratios, 0.47 to 0.88)., Limitations: This study does not determine whether more accurate measures of family history would meaningfully improve estimation of cardiovascular risk., Conclusions: Negative parental history reports were reliable, except for hypertension and high cholesterol levels. Although reports of parental premature heart attack and stroke had high likelihood ratios, their predictive values were low because the prevalence of these conditions was low in parents. If patients were more aware of their parents' medical illnesses, they might be able to estimate their risk for disease more accurately and perhaps motivate themselves to follow a healthy lifestyle.

Objective: To determine whether exercise training in combination with metformin improves cardiovascular risk indices and insulin in comparison to metformin alone among HIV-infected patients., Methods and Design: We conducted a prospective, randomized, 3-month study of HIV patients on stable antiretroviral therapy with hyperinsulinemia and fat redistribution. Subjects received metformin alone or metformin and exercise training consisting of 1 h of aerobic and resistance training three times a week. Cardiovascular parameters, including blood pressure and endurance during sub-maximal stress testing, body composition, strength, insulin and other biochemical parameters were determined., Results: Thirty-seven patients were randomized and 25 subjects completed the study. Subjects receiving exercise training and metformin demonstrated significant decreases in median waist-to-hip ratio [-0.02 (-0.06, -0.01) (median (interquartile range) versus -0.01 (0.03, 0.02), P = 0.026], resting systolic [-12 (-20, -4) versus 0 (-11, 11), P = 0.012] and diastolic blood pressures [-10 (-14, -8) versus 0 (-7, 8), P = 0.001], increased thigh muscle cross-sectional area [3 (-3, 12) versus -7 (-11, 0), P = 0.015], and improved exercise time [3 (0, 4) versus 0 (-1, 1), P = 0.045] compared with subjects receiving metformin alone. Fasting insulin and insulin area under the curve decreased significantly more in the exercise and metformin group (P < 0.05). Lipids and resting lactate did not change significantly between treatment groups., Conclusions: These data demonstrate that exercise training in combination with metformin significantly improves cardiovascular and biochemical parameters more than metformin alone in HIV-infected patients with fat redistribution and hyperinsulinemia. Combined treatment was safe, well tolerated and may be a useful strategy to decrease cardiovascular risk in this population.

Data are sparse regarding long-term outcomes after hospitalization for unstable angina pectoris (UAP) and non-ST-elevation myocardial infarction (NSTEMI), as defined by contemporary criteria. We extended follow-up in a preexisting database of unselected patients with primary UAP and NSTEMI admitted by way of the emergency department from 1991 to 1992. Stepwise Cox models were used to identify multivariate predictors of long-term mortality. There were 275 patients (mean age 66 +/- 12 years, 33% women) who survived to hospital discharge; 134 patients (49%) died during follow-up (median 9.4 years). Significant multivariate predictors of long-term mortality were: age (hazard ratio [HR] per decade 1.7, 95% confidence interval [CI] 1.4 to 1.9); prior MI (HR 1.7, 95% CI 1.2 to 2.5); diabetes (HR 1.7, 95% CI 1.2 to 2.4); congestive heart failure (HR 2.2, 95% CI 1.5 to 3.4); elevated creatinine (HR 2.5, 95% CI 1.7 to 3.8); elevated leukocyte count (HR 1.7, 95% CI 1.1 to 2.5); systolic blood pressure <120 mm Hg at presentation (HR 2.0, 95% CI 1.1 to 3.6); lack of coronary revascularization during the index hospitalization (HR 2.0, 95% CI 1.3 to 3.0); and lack of discharge beta-blocker therapy (HR 1.5, 95% CI 1.1 to 2.2). A clinical prediction rule was generated by assigning weighted point scores for the presence of each significant covariate. Long-term mortality increased markedly with each quintile of score; for quintiles 1 to 5, mortality rates were 8.5%, 29.4%, 47.6%, 75.0%, and 91.5%, respectively (p value for trend <0.001). These data are among the first assessments of long-term mortality after hospitalization for primary UAP and NSTEMI, as defined by contemporary guideline criteria. Easily obtained clinical covariates provide excellent prediction of long-term mortality up to 10 years after hospitalization for primary UAP and NSTEMI.

Background: We sought to assess how cholesterol levels at different ages modify the remaining lifetime risk of coronary heart disease (CHD)., Methods: We included all Framingham Heart Study participants examined from 1971 through 1996 who did not have CHD and were not receiving lipid-lowering therapy. At index ages of 40, 50, 60, 70, and 80 years, participants were stratified by total cholesterol level and by cholesterol subfractions. Lifetime risk of CHD was calculated with death free of CHD as a competing event., Results: Among 3269 men and 4019 women, 1120 developed CHD and 1365 died free of CHD during follow-up. At each index age, lifetime risk of CHD increased with higher cholesterol levels, and time to event decreased. At age 40 years, the lifetime risks of CHD through age 80 years for men with total cholesterol levels less than 200 mg/dL (<5.20 mmol/L), 200 to 239 mg/dL (5.20-6.19 mmol/L), and 240 mg/dL or greater (> or =6.20 mmol/L), respectively, were 31%, 43%, and 57%; for women, the lifetime risks were 15%, 26%, and 33%, respectively. Lifetime risks contrasted sharply with shorter-term risks: at age 40 years, the 10-year cumulative risks of CHD were 3%, 5%, and 12% for men, and 1%, 2%, and 5% for women, respectively., Conclusions: Lifetime risk of CHD increases sharply with higher total cholesterol levels for men and women at all ages. These data support an important role for cholesterol screening in younger patients, and they may help target high-risk patients for lifestyle modification or drug therapy.

Background: A family history of coronary heart disease (CHD) is an independent risk factor for cardiovascular events. However, the mechanisms underlying this susceptibility have not been fully elucidated. We hypothesized that an important mediator of the familial predisposition to CHD is subclinical atherosclerosis, which is detectable by noninvasive imaging., Methods and Results: We studied 1662 subjects (mean age 57, 51% women) in the Framingham Offspring Study who underwent carotid ultrasonography and had both biological parents in the original (parental) cohort. Parental CHD events were validated prospectively by a physician endpoint committee. The associations of carotid intima-media thickness (IMT) with premature parental CHD (occurring before age 60) and any parental CHD (no age restriction) were examined in age- and multivariable-adjusted analyses. Age-adjusted mean internal carotid IMT was higher in subjects who had at least one parent with premature CHD than in those without a validated parental history of premature CHD (men 1.13 versus 1.04 mm, P<0.01; women 0.92 versus 0.85 mm, P=0.03). In both sexes, these differences remained significant after adjustment for cardiovascular risk factors. In analyses without a restriction on parental age of CHD onset, the association between carotid IMT and parental CHD was not statistically significant. There was also no significant association of common carotid IMT with premature or any parental CHD., Conclusions: These findings suggest that subclinical atherosclerosis, assessed in the carotid arteries, is more prevalent in individuals with a family history of CHD. Early-onset parental CHD, in particular, identifies offspring with a strong familial predisposition to atherosclerosis.

Background: Congestive heart failure (CHF) is an increasing public health problem., Methods and Results: Among Framingham Heart Study subjects who were free of CHF at baseline, we determined the lifetime risk for developing overt CHF at selected index ages. We followed 3757 men and 4472 women from 1971 to 1996 for 124 262 person-years; 583 subjects developed CHF and 2002 died without prior CHF. At age 40 years, the lifetime risk for CHF was 21.0% (95% CI 18.7% to 23.2%) for men and 20.3% (95% CI 18.2% to 22.5%) for women. Remaining lifetime risk did not change with advancing index age because of rapidly increasing CHF incidence rates. At age 80 years, the lifetime risk was 20.2% (95% CI 16.1% to 24.2%) for men and 19.3% (95% CI 16.5% to 22.2%) for women. Lifetime risk for CHF doubled for subjects with blood pressure >/=160/100 versus <140/90 mm Hg. In a secondary analysis, we only considered those who developed CHF without an antecedent myocardial infarction; at age 40 years, the lifetime risk for CHF was 11.4% (95% CI 9.6% to 13.2%) for men and 15.4% (95% CI 13.5% to 17.3%) for women., Conclusions: When established clinical criteria are used to define overt CHF, the lifetime risk for CHF is 1 in 5 for both men and women. For CHF occurring in the absence of myocardial infarction, the lifetime risk is 1 in 9 for men and 1 in 6 for women, which highlights the risk of CHF that is largely attributable to hypertension. These results should assist in predicting the population burden of CHF and placing greater emphasis on prevention of CHF through hypertension control and prevention of myocardial infarction.

Background: Cardiovascular mortality is high in individuals with end-stage renal disease. However, less is known about the prognostic importance of moderate renal insufficiency in patients with acute myocardial infarction., Methods: We studied all patients with acute myocardial infarction admitted through the emergency department to an urban, academic hospital over 1 year. Patients were classified as having elevated (>133 micromol/L [1.5 mg/dL]) or normal (< or =133 micromol/L) serum creatinine at presentation., Results: Of 483 patients, 22% had elevated creatinine and 78% had normal creatinine. By 1 year, 46% of patients with elevated creatinine and 15% of patients with normal creatinine had died (P <.001). The unadjusted hazard ratio for 1-year mortality was increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 3.85, 95% CI 2.61-5.67). After adjustment for baseline characteristics and treatment, the multivariable-adjusted hazard ratio for 1-year mortality remained increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 2.40, 95% CI 1.55-3.72). There was an important modification of the prognostic value of creatinine by the presence of congestive heart failure at presentation (P value for interaction =.04). The adjusted hazard ratio for 1-year death associated with elevated creatinine compared with normal creatinine was 3.89 (95% CI 1.87-8.07) in patients without congestive heart failure and 1.92 (95% CI 1.10-3.36) in patients with congestive heart failure., Conclusions: Elevated serum creatinine at presentation is associated with 1-year mortality after acute myocardial infarction. Further study is needed to optimize treatment after myocardial infarction in this high-risk group.

Cross-sectional national data indicate poor levels of treatment and control of hypertension. We identified factors that prospectively predict initiation of antihypertensive therapy and attainment of blood pressure control in the community. We included all Framingham Heart Study subjects examined between 1987 and 1999 who had untreated or uncontrolled hypertension (systolic > or =140 or diastolic > or =90 mm Hg) at a baseline examination and presented for follow-up examination 4 years later. Clinical covariates were examined for their association with initiation or control at follow-up. Among 1103 hypertensive participants who were untreated at baseline, 350 (31.7%) subjects were receiving therapy at follow-up, including 25.7% of subjects with stage 1 and 51.2% of those with stage > or =2 hypertension at baseline. Multivariate predictors of initiation of therapy included higher systolic and diastolic pressure, prevalent and interim cardiovascular disease, and left ventricular hypertrophy. Other cardiovascular risk factors did not predict initiation of treatment. Among 2475 hypertensive participants who were uncontrolled (treated or untreated) at baseline, 988 (39.9%) were controlled at follow-up. Prevalent cardiovascular disease and interim initiation of therapy predicted control; older age and higher baseline systolic levels predicted lack of control. These data provide estimates of longitudinal rates of treatment and control of hypertension in the community. It appears that global risk was not taken into consideration when making decisions for initiation of therapy. Greater emphasis is needed on achieving blood pressure control in all patients but particularly among older subjects and those with systolic hypertension.