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B M Psaty

Publications and source records attributed to B M Psaty.

At least 109 records · Page 6Linked to original sources
PubMed1997

Effect size and power for clinical trials that measure years of healthy life.

Some clinical trials perform repeated measurements on patients over time, plot those measures against time, and summarize the results in terms of the area under the curve. If the measured variable is health status, the summary outcome is sometimes referred to as years of healthy life (YHL), or quality-adjusted life years (QALY). This paper investigates some theoretical and practical aspects of randomized trials designed to assess measures such as YHL. We first derived algebraic expressions for the effect size of YHL measures under several theoretical models of the treatment's effect on health. We used these expressions to examine how the length of the study, the number of measurements per person and the correlations among health measurements over time influence the effect size. We also explored the relative statistical power of analyses based on YHL versus analyses based on change-scores using the same data. We present an example. Findings suggest that: (i) the number of measurements per person need not be large; (ii) high correlation among measures over time tends to lower the power of a study using YHL; (iii) a longer study will not always provide more power than a shorter study, and (iv) analyses based on YHL may have less power than change-score analyses. Some of these findings depend on the model of change in health status caused by the treatment. Such models require further study.

Effect Modifier, Epidemiologic↗
PubMed1997

Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women.

Factor V Leiden (factor V Arg506Gln), the genetic defect underlying resistance to activated protein C, is the most common risk factor for venous thrombosis. The relationship between this genetic abnormality and arterial disease is still unresolved. To assess whether factor V Leiden increases the risk of myocardial infarction (MI), we conducted a population-based case-control study among women 18 to 44 years of age in western Washington state. We included 84 women with first MI and 388 control women, ie, women residing in the same area in the same age range without MI (n = 388). The control women were contacted by random digit dialing. Data on risk factor status were collected via personal interview, and data on the factor V genotype via polymerase chain reaction techniques. The factor V Leiden mutation was found more often in women with MI (10%) than among controls (4%). The odds ratio for MI was 2.4 [95% confidence interval (CI) 1.0 to 5.9]. The risk was increased fourfold (CIgs 1.2 to 12.1) when adjusted for major cardiovascular risk factors. Among nonsmokers the factor V Leiden mutation had little effect (odds ratio 1.1, CI95 0.1 to 8.5), whereas it had a large effect among smokers (odds ratio 3.6, CI95 0.9 to 14.4), which, because smoking was itself a strong risk factor for MI, led to an odds ratio for smoking carriers of the mutation that was 32-fold increased compared with nonsmoking noncarriers. We conclude that factor V Leiden increases the risk of MI in young women. This effect seems to be confined largely to current smokers.

Adult↗
PubMed1997

Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis.

OBJECTIVE: To review the scientific evidence concerning the safety and efficacy of various antihypertensive therapies used as first-line agents and evaluated in terms of major disease end points. DATA SOURCES: MEDLINE searches and previous meta-analyses for 1980 to 1995. DATA SELECTION: We selected long-term studies that assessed major disease end points as an outcome. For the meta-analysis, we chose placebo-controlled randomized trials. For randomized trials using surrogate end points such as blood pressure, we selected the largest studies that evaluated multiple drugs. Where clinical trial evidence was lacking, we relied on information from observational studies. DATA SYNTHESIS: Diuretics and beta-blockers have been evaluated in 18 long-term randomized trials. Compared with placebo, beta-blocker therapy was effective in preventing stroke (relative risk [RR], 0.71; 95% confidence interval [CI], 0.59-0.86) and congestive heart failure (RR, 0.58; 95% CI, 0.40-0.84). The findings were similar for high-dose diuretic therapy (for stroke, RR, 0.49; 95% CI, 0.39-0.62; and for congestive heart failure, RR, 0.17; 95% CI, 0.07-0.41). Low-dose diuretic therapy prevented not only stroke (RR, 0.66; 95% CI, 0.55-0.78) and congestive heart failure (RR, 0.58; 95% CI, 0.44-0.76) but also coronary disease (RR, 0.72; 95% CI, 0.61-0.85) and total mortality (RR, 0.90; 95% CI, 0.81-0.99). Although calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure in hypertensive patients, the clinical trial evidence in terms of health outcomes is meager. For several short-acting dihydropyridine calcium channel blockers, the available evidence suggests the possibility of harm. Whether the long-acting formulations and the nondihydropyridine calcium channel blockers are safe and prevent major cardiovascular events in patients with hypertension remains untested and therefore unknown. CONCLUSION: Until the results of large long-term clinical trials evaluating the effects of calcium channel blockers and ACE inhibitors on cardiovascular disease incidence are completed, the available scientific evidence provides strong support for the current national guidelines, which recommend diuretics and beta-blockers as firstline agents and low-dose therapy for all antihypertensive agents.

Adrenergic beta-Antagonists↗
PubMed1997

Hostility, aggression and the risk of nonfatal myocardial infarction in postmenopausal women.

Hostility can predict coronary heart disease (CHD) and total mortality in men. However, in women this association has not been as thoroughly explored. This study examines whether hostile and aggressive attitudes are associated with myocardial infarction (MI) in postmenopausal women. Cases included 277 women who presented with an incident MI. Controls included a random sample of 988 female health maintenance organization enrollees. Women were asked the Hostile-Affect and the Aggressive-Responding factors of the Cook-Medley Hostility Scale. The Hostile-Affect score was linearly associated with increased risk for MI (odds ratio [OR] per point = 1.22; 95% confidence interval [CI95%] = 1.07-1.38), whereas the Aggressive-Responding score had a modest protective effect (OR = 0.92 per point; CI95% = 0.84-1.02); p = 0.009. Adjustment for sociodemographic and MI risk factors altered these results only slightly. These hostility measures are easily administered, and could help to identify women who are at high risk for CHD and who may benefit from preventive measures.

Adult↗
PubMed1997

Willingness to pay for antihypertensive care: evidence from a staff-model HMO.

Willingness to pay (WTP) has been used in Sweden to evaluate the value of antihypertensive therapy. The Swedish studies indicate that hypertensive patients are willing to pay between $107 and $120 per month for their therapy. We conducted a similar study in a population of hypertensive patients in a large, staff-model, managed care organization (Group Health Cooperative of Puget Sound). Participants returned a postal survey containing a WTP question with 10 "bids" ranging from $25 to $250. Respondents recorded whether they would accept or reject each bid at the stated dollar value. Demographic information such as age, income, and perceived health status was also collected. Results were analyzed with ordinary least squares regression, controlling for the demographic data. The estimated parameters were significant and indicated an adjusted mean WTP of $93 per month for antihypertensive therapy. The close similarity of the Swedish and U.S. results appears to support the use of WTP as a measure of health state preferences.

Age Factors↗
PubMed1997

The association of antihypertensive medication with serum creatinine changes in older adults.

Many of the potential effects of antihypertensive therapy, including renal function, have been inadequately investigated in clinical trials in older adults. In an observational study, we examined the association between treatment with various classes of antihypertensive agents and 3-year changes in serum creatinine in 1296 older adults with treated hypertension and without prior renal disease (mean age 72.2 years; 60% female; 30% diabetic; 42% with cardiovascular disease (CVD)) from the Cardiovascular Health Study. Baseline antihypertensive medications included thiazides (HCT), beta-adrenergic blockers, angiotensin converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), vasodilators (VAS), HCT + BB, HCT + ACE-I, HCT + CCB, HCT + VAS, loop diuretics (LOOP), and other combinations. Unadjusted results indicated that minimal changes in mean serum creatinine occurred over time for all therapies and only a few changes were statistically significant (HCT: +0.02 mg/dL, ACE-I: +0.04, CCB: +0.04; all P < .05; LOOP: +0.06 mg/dL; P < .001). In multivariate analyses with HCT users as the reference group and adjusting for baseline serum creatinine, age, sex, smoking, diabetes mellitus, CVD, height, weight, common carotid intima-media thickness, and use of allopurinol, phenytoin, cimetidine, and nonsteroidal antiinflammatory drugs, all of the relative changes were small and statistically nonsignificant except for HCT + VAS users (+0.07 mg/dL; P < .05). When users of the same therapy at baseline and follow-up were restricted, only LOOP users had significant albeit small changes in serum creatinine (+0.05 mg/dL; P < .05). Although results from clinical trials are needed to confirm these findings, these observational data suggest no major differences between specific antihypertensive therapies in 3-year serum creatinine changes in older adults without prior renal disease.

Aged↗
PubMed1997

Caffeine intake in relation to the risk of primary cardiac arrest.

We conducted a population-based case-control study in King County, WA, to evaluate the association between usual caffeine intake and primary cardiac arrest. We identified primary cardiac arrest cases (N = 362) without a history of clinical heart disease or major comorbidity through paramedic incident reports during the period 1988-1994. We identified controls (N = 581), individually matched to cases on age (+/-7 years) and gender and meeting the same general health criteria, through random digit dialing. We interviewed the spouses of cases and controls to obtain information on usual caffeine intake from coffee, tea, and cola during the prior year. After adjusting for cigarette smoking and other risk factors, we observed little association between daily consumption of the caffeine equivalent of fewer than 5 cups per day of drip coffee (< 687 mg per day) and primary cardiac arrest. High usual caffeine consumption (> or = 687 mg per day) was associated with a modestly elevated risk of primary cardiac arrest [odds ratio = 1.44; 95% confidence interval (CI) = 0.82-2.53]. The elevated risk associated with high caffeine consumption appeared to be restricted to never-smokers (odds ratio for > or = 687 mg per day = 3.2; 95% CI = 1.3-8.1).

Adult↗
PubMed1997

Clinical implications of the World Health Organization-International Society of Hypertension statement on calcium antagonists.

The controversy over the efficacy and safety of calcium antagonists is over 2 years old. Since millions of patients worldwide are currently using calcium antagonists for the treatment of high blood pressure and angina, a systematic review of their potential risks and benefits is much needed. In response to this need, the World Health Organization (WHO) and the International Society of Hypertension (ISH) recently convened an ad-hoc subcommittee to review the available evidence (J Hypertens 1997, 15:105-115). Importantly, the WHO-ISH statement does take a strong stand in favor of large long-term trials that compare antihypertensive agents, and we all agree that these comparative trials are urgently needed. However, the WHO-ISH statement is marred in part by errors of omission, by the selective use of evidence and epidemiologic principles, and by a narrow application of the viewpoint of those who believe that evidence can come only from the results of megatrials. As a result, practicing clinicians will find more useful information in existing hypertension and postmyocardial infarction guidelines (Arch Intern Med 1993, 153:154-183 and JAm Coll Cardiol 1996, 28:1328-1428).

Calcium Channel Blockers↗
PubMed1997

The association of antihypertensive agents with MRI white matter findings and with Modified Mini-Mental State Examination in older adults.

OBJECTIVES: To examine the association of antihypertensive regimen with magnetic resonance imaging (MRI) white matter hyperintensity and with cognitive impairment in older adults. DESIGN: Cross-sectional study. SETTING: The Cardiovascular Health study, an observational prospective cohort study of risk factors for coronary heart disease and stroke in men and women 65 years of age and older. PARTICIPANTS: 1268 men and women with pharmacologically treated hypertension. MEASUREMENTS: Information on medication use, medical history, and health habits was collected at clinic examinations. Participants completed the Modified Mini-Mental State Examination (3MS) and underwent MRI examination. Without clinical information, study neuroradiologists assigned an overall grade of white matter signal intensity on MRI on a scale from 0 (no findings) to 9 (extensive findings). RESULTS: Adjusted mean white matter grade was higher for users of calcium channel blockers (2.59, P = .007) and users of loop diuretics (2.60, P = .015) than for users of beta blockers (2.12). The association was present for both dihydropyridine and non-dihydropyridine calcium channel blockers. Adjusted mean 3MS scores were lower for users of calcium channel blockers (89.6, P < .002), especially dihydropyridines, and users of loop diuretics (89.7, P < .006) than for users of beta blockers (92.3). No statistically significant association could be shown for users of other drug regimens, including thiazides and ACE inhibitors. CONCLUSION: In this study, users of antihypertensive regimens which included calcium channel blockers or loop diuretics had more severe white matter hyperintensity on MRI and worse performance on 3MS than users of beta blockers.

Adrenergic beta-Antagonists↗
PubMed1997

Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects.

Blood levels of C-reactive protein (CRP), a marker of inflammation, are related to cardiovascular disease risk. To determine cross-sectional correlates in the elderly, we measured CRP in 400 men and women older than 65 years and free of clinical cardiovascular disease at baseline as part of the Cardiovascular Health Study. Only 2% of the values were greater than 10 mg/L, the cut-point usually used to identify inflammation. CRP levels appeared tightly regulated, since there were strong bivariate correlations between CRP and the following: inflammation-sensitive proteins such as fibrinogen (r = .52); measures of fibrinolysis such as plasmin-antiplasmin complex (r = .23); pack-years of smoking (r = .30); and body mass index (r = .24; all P values < or = .001). The association with pack-years was independent of the length of time since cessation of smoking. CRP levels were also associated with coagulation factors VIIc, IXc, and Xc; HDL cholesterol (negative) and triglyceride; diabetes status; diuretic use; ECG abnormalities; and level of exercise. Because of effect modification, two multiple linear regression prediction models were developed for CRP, one each for never smokers and ever smokers. An a priori physiologic model was used to guide these analyses, which disallowed the use of other inflammation-sensitive variables such as fibrinogen. In never smokers, the independent predictors were body mass index (+), diabetes status (+), plasmin-antiplasmin complex (+), and the presence of ECG abnormalities (+); this model predicted 15% of the CRP population variance. In ever smokers, the predictors were body mass index (+), plasmin-antiplasmin complex (+), pack-years of smoking (+), HDL cholesterol (-), and ankle-arm blood pressure index (-); this model predicted 42% of the population variance. We conclude that levels of CRP in the healthy elderly are tightly regulated and reflect lifetime exposure to smoking as well as level of obesity, ongoing level of fibrinolysis, diabetes status, and level of subclinical atherothrombotic disease. Moreover, exposure to smoking affects the relation of CRP to these other factors.

Aged↗
PubMed1997

Relationship of C-reactive protein to risk of cardiovascular disease in the elderly. Results from the Cardiovascular Health Study and the Rural Health Promotion Project.

Markers of inflammation, such as C-reactive protein (CRP), are related to risk of cardiovascular disease (CVD) events in those with angina, but little is known about individuals without prevalent clinical CVD. We performed a prospective, nested case-control study in the Cardiovascular Health Study (CHS; 5201 healthy elderly men and women). Case subjects (n = 146 men and women with incident CVD events including angina, myocardial infarction, and death) and control subjects (n = 146) were matched on the basis of sex and the presence or absence of significant subclinical CVD at baseline (average follow-up, 2.4 years). In women but not men, the mean CRP level was higher for case subjects than for control subjects (P < or = .05). In general, CRP was higher in those with subclinical disease. Most of the association of CRP with female case subjects versus control subjects was in the subgroup with subclinical disease; 3.33 versus 1.90 mg/L, P < .05, adjusted for age and time of follow-up. Case-control differences were greatest when the time between baseline and the CVD event was shortest. The strongest associations were with myocardial infarction, and there was an overall odds ratio for incident myocardial infarction for men and women with subclinical disease (upper quartile versus lower three quartiles) of 2.67 (confidence interval [CI] = 1.04 to 6.81), with the relationship being stronger in women (4.50 [CI = 0.97 to 20.8]) than in men (1.75 [CI = 0.51 to 5.98]). We performed a similar study in the Rural Health Promotion Project, in which mean values of CRP were higher for female case subjects than for female control subjects, but no differences were apparent for men. Comparing the upper quintile with the lower four, the odds ratio for CVD case subjects was 2.7 (CI = 1.10 to 6.60). In conclusion, CRP was associated with incident events in the elderly, especially in those with subclinical disease at baseline.

Aged↗
PubMed1997

Thrombosis in the young: effect of atherosclerotic risk factors on the risk of myocardial infarction associated with prothrombotic factors.

Myocardial infarction in the young provides a unique model for the investigation of potential interactions between atherosclerotic and prothrombotic risk factors. Because myocardial infarction reflects atherothrombotic disease, it is important to take into account factors related to atherosclerosis when examining prothrombotic factors as potential determinants of myocardial infarction. In Western societies, there are increases in both the prevalences of metabolic risk factors and atherosclerotic coronary disease with aging. The clinical expression of the thrombotic risk associated with heritable factors, such as factor V Leiden, as myocardial infarction appears to occur only in the presence of other risk factors, such as smoking and known metabolic risk factors related to atherosclerosis. If confirmed in other studies of factor V Leiden and with other mutations related to prothrombotic risk, these observations will likely have both etiologic and practical consequences. Finally, we suggest that efforts to determine whether a prothrombotic risk factor contributes "independently" to the risk of myocardial infarction may lead to a significant underestimation of the importance of the factor in the occurrence of myocardial infarction, particularly among clinically-important subsets of the population.

Adult↗
PubMed1996

Clinically silent electrocardiographic abnormalities and risk of primary cardiac arrest among hypertensive patients.

BACKGROUND: Whether continuous ECG indexes that reflect the severity of left ventricular hypertrophy (LVHI), myocardial injury (CIIS), and QT-interval prolongation (QTI) are associated with the risk of primary cardiac arrest among hypertensive patients, independent of conventional binary ECG criteria, remains unknown. METHODS AND RESULTS: We conducted a population-based case-control study among patients who were free of clinically recognized heart disease and who received care at a health maintenance organization. Cases (n = 131) were treated hypertensive patients who had had a primary cardiac arrest between 1977 and 1990. Controls (n = 562) were a stratified random sample of treated hypertensive patients. Resting ECGs were reviewed to estimate the severity of left ventricular hypertrophy, myocardial injury, and QT-interval prolongation on the basis of the algorithms of the Novacode ECG classification system. After adjustment for other risk factors and binary ECG criteria for the abnormalities, the LVHI, CIIS, and QTI scores were directly related to the risk of primary cardiac arrest. In a comparison of the 80th with the 20th percentile score for the LVHI, the risk was increased 40% (odds ratio, 1.4; 95% CI, 1.0 to 2.0); for the CIIS, the risk was increased 70% (odds ratio, 1.7; 95% CI, 1.2 to 2.5); and for the QTI, the risk was increased 80% (odds ratio, 1.8; 95% CI, 1.3 to 2.7). CONCLUSIONS: Our findings suggest that continuous ECG indexes that reflect left ventricular hypertrophy, myocardial injury, and QT-interval prolongation are directly related to the risk of primary cardiac arrest among hypertensive patients without clinically recognized heart disease. Binary ECG criteria may underestimate the prognostic importance of these pathophysiological abnormalities.

Adult↗
PubMed1996

Association of fibrinogen and coagulation factors VII and VIII with cardiovascular risk factors in the elderly: the Cardiovascular Health Study. Cardiovascular Health Study Investigators.

The cross-sectional correlates of three hemostatic factors--fibrinogen, factor VII, and factor VIII--were examined in the Cardiovascular Health Study, a population-based cohort study of 5,201 subjects over age 65 years. Subjects were recruited in 1989-1990 in Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. In multivariate linear regression models, cardiac risk factors significantly associated with fibrinogen were current smoking, race, lipids, and white blood count. In women, alcohol use, obesity, physical activity, and insulin level were also significant, while in men hypertension was correlated. The significant correlates of factor VII were lipids and white blood count in men and estrogen use, alcohol use, race, lipids, insulin level, white blood count, and obesity in women. The independent correlates of factor VIII were insulin, glucose, and race in both sexes; low density lipoprotein cholesterol, white blood count, and diuretic use in men; and alcohol use in women. In multivariate models, factors known to be modifiable risk factors for cardiovascular disease accounted for more of the population variance of these hemostatic factors in women than in men, especially for factor VII. The hemostatic factors may mediate some effects of risk factors on disease, and this should be considered in longitudinal studies.

Age Distribution↗