Biomedical subjects

Donald M Lloyd-Jones

Publications and source records attributed to Donald M Lloyd-Jones.

At least 19 recordsLinked to original sources

PubMed2026

Estimating population structure using epigenome-wide methylation data.

Population stratification is one of the source of inflation in epigenome-wide association studies (EWAS) when not properly accounted for. To address this, we developed methylation population scores (MPSs) to predict genetic principal components (GPCs) using a feature selection approach. We used multi-ethnic DNA methylation data from Illumina EPIC arrays across five cohorts, including MESA (n = 929), CARDIA (n = 1123), JHS (n = 1365), ARIC (n = 2338), and HCHS/SOL (n = 1475), randomly splitting participants into training (85%) and test (15%) sets. Within each cohort, associations between GPCs and CpG sites were estimated using linear regression adjusting for age, sex, smoking and alcohol use, race/ethnicity, body mass index, and cell type proportions, followed by meta-analysis and selection of CpGs with FDR <0.05. We then applied a two-stage weighted least squares Lasso regression to construct MPSs, adjusting for the aforementioned covariates. In the test dataset, MPSs showed strong correlation with GPCs, with R² ranging from 0.27 (MPS7 vs. GPC7) to 0.98 (MPS1 vs. GPC1). Visualization demonstrated that MPSs recapitulated the pattern shown by GPCs in differentiating self-reported White, Black, and Hispanic/Latino groups and outperformed methylation-based principal components constructed using alternative published methods. Additionally, MPSs showed comparable performance to GPCs in reducing inflation in EWAS. Overall, MPSs uses supervised learning with covariate adjustment to capture genetic structure across diverse populations, and provide a reliable estimate of population structure in the data and can complement GPCs when genetic data are absent.

Humans↗

PubMed2025

Estimating population structure using epigenome-wide methylation data.

INTRODUCTION: In epigenome-wide association analysis (EWAS), unaddressed population stratification often leads to inflation. We aimed to compute methylation population scores (MPSs) that predict genetic principal components (GPCs) using a feature selection and regression approach. METHODS: We used multi-ethnic methylation data (Illumina 450K/EPIC array) from unrelated MESA (n=929), CARDIA (n=1123), JHS (n=1365), ARIC (n=2338), and HCHS/SOL (n=1475) individuals, randomly assigning 85% of participants from each cohort to a training dataset and the remaining 15% to a test dataset. First, we estimated the associations of GPCs with each available CpG methylation site using linear regression within each cohort, adjusting for age, sex, smoking status, race/ethnic background (as a proxy for background information associated with lifestyle and other environmental exposures that may impact methylation), alcohol use status, body mass index, and cell type proportions. We meta-analyzed the associations across cohorts and selected CpG sites with association FDR-adjusted q-value <0.05. We next aggregated individuallevel data across the cohort-specific training datasets, and applied two-stage weighted least squares Lasso regression, with the GPCs as the outcomes and the selected CpG sites as penalized predictors, adjusting for the aforementioned covariates. The developed MPSs are the weighted sum of selected CpG sites from the Lasso. To evaluate the developed MPSs, we constructed them in the test dataset, and compared them with GPCs, and with MPSs constructed based on a previously-published paper. Comparison was based on correlation analysis and data visualization. We demonstrate the use of the MPSs in EWAS. RESULTS: In the test dataset, the MPSs were highly correlated with GPCs, with correlation decreasing, though not monotonically, for later components. Specifically, MPS1 and GPC1 had R2= 0.99, while MPS7 and GPC7 had R2=0.27 (the lowest observed correlation). In data visualization, MPSs had similar patterns as GPCs in differentiating self-reported White, Black, and Hispanic/Latino groups, while outperforming MPC constructed using alternative published methods. MPSs showed comparable performance to GPCs in reducing some of the inflation in EWAS. CONCLUSIONS: Methylation-based population scores provide a reliable estimate of population structure in the data and can complement GPCs when genetic data are absent. Unlike previous methods based on unsupervised methylation PCA, MPSs uses supervised learning with covariate adjustment to capture genetic structure across diverse populations. The weights for each GPCs derived in our study can be applied to generate MPSs in other studies.

Journal Article↗

PubMed2025

Unveiling the Genetic Landscape of Coronary Artery Disease Through Common and Rare Structural Variants.

BACKGROUND: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear. METHOD AND RESULTS: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program. Single variant tests were performed on 58 706 SVs in a study sample of 11 556 CAD cases and 42 907 controls. Additionally, aggregate tests using sliding windows were performed to examine rare SVs. One genome-wide significant association was identified for a common biallelic intergenic duplication on chromosome 6q21 (P=1.54E-09, odds ratio=1.34). The sliding window-based aggregate tests found 1 region on chromosome 17q25.3, overlapping USP36, to be significantly associated with coronary artery disease (P=1.03E-10). USP36 is highly expressed in arterial and adipose tissues while broadly affecting several cardiometabolic traits. CONCLUSIONS: Our results suggest that SVs, both common and rare, may influence the risk of coronary artery disease.

Humans↗

PubMed2007

Association of atrial fibrillation and amino-terminal pro-brain natriuretic peptide concentrations in dyspneic subjects with and without acute heart failure: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study.

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.

Aged↗

PubMed2006

National Cholesterol Education Program risk assessment and potential for risk misclassification.

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.

Adult↗

PubMed2006

Predicting cardiovascular risk: so what do we do now?

Explore the source record for details and available documents.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2006

Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease.

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.

Algorithms↗

PubMed2006

Comparison of risk factors for cardiovascular mortality in black and white adults.

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.

Adult↗

PubMed2006

Utility of amino-terminal pro-brain natriuretic peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department.

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.

Age Factors↗

PubMed2006

Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age.

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.

Age Factors↗

PubMed2006

Comparison of long-term mortality across the spectrum of acute coronary syndromes.

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.

Age Distribution↗

PubMed2006

Short-term versus long-term risk for coronary artery disease: implications for lipid guidelines.

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.

Algorithms↗

PubMed2006

Preventing cardiovascular disease in the 21st century: therapeutic and preventive implications of current evidence.

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.

Cardiovascular Diseases↗

PubMed2005

Implications of changing national cholesterol education program goals for the treatment and control of hypercholesterolemia.

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.

Adult↗

PubMed2005

Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study.

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.

Aged↗

PubMed2005

Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial.

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.

Adrenergic beta-Antagonists↗

PubMed2005

Usefulness of the TIMI Risk Index in predicting short- and long-term mortality in patients with acute coronary syndromes.

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.

Aged↗

PubMed2005

Ethnic variation in hypertension among premenopausal and perimenopausal women: Study of Women's Health Across the Nation.

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.

Adult↗