ACE-inhibitor therapy and nosocomial pneumonia.
Explore the source record for details and available documents.
Angiotensin-Converting Enzyme Inhibitors↗
Biomedical subjects
B M Psaty
Publications and source records attributed to B M Psaty.
Assessment and control for confounding by indication in observational studies.
In the evaluation of pharmacologic therapies, the controlled clinical trial is the preferred design. When clinical trial results are not available, the alternative designs are observational epidemiologic studies. A traditional concern about the validity of findings from epidemiologic studies is the possibility of bias from uncontrolled confounding. In studies of pharmacologic therapies, confounding by indication may arise when a drug treatment serves as a marker for a clinical characteristic or medical condition that triggers the use of the treatment and that, at the same time, increases the risk of the outcome under study. Confounding by indication is not conceptually different from confounding by other factors, and the approaches to detect and control for confounding--matching, stratification, restriction, and multivariate adjustment--are the same. Even after adjustment for known risk factors, residual confounding may occur because of measurement error or unmeasured or unknown risk factors. Although residual confounding is difficult to exclude in observational studies, there are limits to what this "unknown" confounding can explain. The degree of confounding depends on the prevalence of the putative confounding factor, the level of its association with the disease, and the level of its association with the exposure. For example, a confounding factor with a prevalence of 20% would have to increase the relative odds of both outcome and exposure by factors of 4 to 5 before the relative risk of 1.57 would be reduced to 1.00. Observational studies have provided important scientific evidence about the risks associated with several risk factors, including drug therapies, and they are often the only option for assessing safety. Understanding the methods to detect and control for confounding makes it possible to assess the plausibility of claims that confounding is an alternative explanation for the findings of particular studies.
Antihypertensive Agents↗
Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study.
Coagulation factor levels predict arterial thrombosis in epidemiological studies, but studies of older persons are needed. We studied 3 plasma antigenic markers of fibrinolysis, viz, plasminogen activator inhibitor-1 (PAI-1), fibrin fragment D-dimer, and plasmin-antiplasmin complex (PAP) for the prediction of arterial thrombosis in healthy elderly persons over age 65. The study was a nested case-control study in the Cardiovascular Health Study cohort of 5201 men and women >/=65 years of age who were enrolled from 1989 to 1990. Cases were 146 participants without baseline clinical vascular disease who developed myocardial infarction, angina, or coronary death during a follow-up of 2.4 years. Controls remained free of cardiovascular events and were matched 1:1 to cases with respect to sex, duration of follow-up, and baseline subclinical vascular disease status. With increasing quartile of D-dimer and PAP levels but not of PAI-1, there was an independent increased risk of myocardial infarction or coronary death, but not of angina. The relative risk for D-dimer above versus below the median value (>/=120 microg/L) was 2.5 (95% confidence interval, 1.1 to 5.9) and for PAP above the median (>/=5.25 nmol/L), 3.1 (1.3 to 7.7). Risks were independent of C-reactive protein and fibrinogen concentrations. There were no differences in risk by sex or presence of baseline subclinical disease. D-dimer and PAP, but not PAI-1, predicted future myocardial infarction in men and women over age 65. Relationships were independent of other risk factors, including inflammation markers. Results indicate a major role for these markers in identifying a high risk of arterial disease in this age group.
Age Factors↗
Relationship of plasmin generation to cardiovascular disease risk factors in elderly men and women.
Plasmin-alpha2-antiplasmin complex (PAP) marks plasmin generation and fibrinolytic balance. We recently observed that elevated levels of PAP predict acute myocardial infarction in the elderly, yet little is known about the correlates of PAP. We measured PAP in 800 elderly subjects who were free of clinical cardiovascular disease in 2 cohort studies: the Cardiovascular Health Study and the Honolulu Heart Program. Median PAP levels did not differ between the Cardiovascular Health Study (6.05+/-1.46 nmol/L) and the Honolulu Heart Program (6.11+/-1.44 nmol/L), and correlates of PAP were similar in both cohorts. In CHS, PAP levels increased with age (r=0. 30), procoagulant factors (eg, factor VIIc, r=0.15), thrombin activity (prothrombin fragment F1+2, r=0.29), and inflammation-sensitive proteins (eg, fibrinogen, r=0.44; factor VIIIc, r=0.37). PAP was associated with increased atherosclerosis as measured by the ankle-arm index (AAI) (P for trend, </=0.001). PAP was negatively related to factors associated with the insulin resistance syndrome (IRS) (eg, fasting insulin, r=-0.26; body mass index, r=-0.26), possibly reflecting an association with plasminogen activator inhibitor-1 (r=-0.29). Although our study did not have sufficient power to detect a significant interaction, PAP and AAI appeared to be more weakly associated in subjects with more manifestations of the IRS: PAP appeared more strongly associated with AAI in the subgroup with 0 or 1 metabolic disorders (P</=0.001; slope estimate, -0.14) compared with the subgroup with 2 or more metabolic disorders (P=0.10; slope estimate, -0.08) and in those with non-insulin-dependent diabetes mellitus (P=0.46; slope estimate, -0.04). Although PAP reflects reactive fibrinolysis and is associated with subclinical atherosclerosis, this relationship may be weaker in populations with characteristics of the IRS, possibly reflecting the inhibitory effects of plasminogen activator inhibitor-1 on PAP. Decreased fibrinolysis in the presence of subclinical disease in subjects with hyperinsulinemia or glucose intolerance is consistent with the premise that depressed plasmin generation may enhance the progression of atherosclerosis in these people.
Aged↗
Hormone replacement therapy, inflammation, and hemostasis in elderly women.
Lipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the assumed coronary risk reduction associated with therapy. To explore other possible mechanisms, we studied associations of HRT use with inflammation and hemostasis risk markers in women >/=65 years of age. Subjects were selected from 3393 participants in the fourth year examination of the Cardiovascular Health Study, an observational study of vascular disease risk factors. After excluding women with vascular disease, we compared levels of inflammation and hemostasis variables in the 230 women using unopposed estrogen and 60 using estrogen/progestin, with those of 196 nonusers selected as controls. Compared with nonusers, unopposed estrogen use was associated with 59% higher mean C-reactive protein (P<0.001), but with modestly lower levels of other inflammation indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was 16% higher among estrogen users (P<0.001), but this was not associated with higher thrombin production (prothrombin fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50% lower in both using groups (P<0.001) compared with nonusers, and this was associated with higher plasmin-antiplasmin complex: 8% higher in estrogen and 18% higher in estrogen/progestin users (P<0. 05). Relationships between the markers and hormone use were less pronounced in estrogen/progestin users, with no association for C-reactive protein except in women in upper 2 tertiles of body mass index (P for interaction, 0.02). The direction and strength of the associations of HRT use with inflammation markers differed depending on the protein, so it is not clear whether HRT confers coronary risk reduction through an inflammation-sensitive mechanism. Associations with hemostasis markers indicated no association with evidence of procoagulation and a possible association with increased fibrinolytic activity.
Aged↗
Blood pressure level and incidence of myocardial infarction among patients treated for hypertension.
OBJECTIVES: This study examined the relationship between achieved blood pressure and risk of myocardial infarction among patients treated for hypertension. METHODS: Blood pressure and other cardiovascular risk factors were assessed among 718 myocardial infarction case patients and 2136 matched controls. RESULTS: Blood pressure level was directly related to risk of myocardial infarction. Patients with treated hypertension who had mild elevations in blood pressure accounted for a larger share of the excess myocardial infarction incidence than those who had higher blood pressure readings. CONCLUSIONS: Achieving normotensive levels in treated hypertensive patients with uncontrolled blood pressure might prevent more than 15% of myocardial infarctions in the treated hypertensive population.
Aged↗
Antidiabetic treatment trends in a cohort of elderly people with diabetes. The cardiovascular health study, 1989-1997.
OBJECTIVE: This study characterizes the pharmaceutical treatment of type 2 diabetes from 1989-1990 to 1996-1997 in an elderly cohort. RESEARCH DESIGN AND METHODS: A total of 5,888 adults aged > or = 65 years were recruited and attended a baseline clinic visit in 1989-1990 (n = 5,201, original cohort) or 1992-1993 (n = 687. African-American [new] cohort) as participants of the Cardiovascular Health Study. Fasting serum glucose (FSG) was measured at baseline. Medication use was ascertained by drug inventory at all annual clinic visits. Diabetes was defined at baseline as insulin or oral hypoglycemic agent (OHA) use or as having an FSG > or = 7.0 mmol/l (126 mg/dl), the current consensus definition of diabetes. RESULTS: A total of 387 (7%) original (FSG = 9.8 mmol/l [177 mg/dl]) and 115 (17%) new (FSG = 10.6 mmol/l [191 mg/dl]) cohort members had pharmacologically treated diabetes at baseline. Among those in the original and in the new cohorts who survived follow-up, respectively, OHA use decreased from 80 to 48% (P < 0.001) and from 67 to 50% (P < 0.003) and insulin use increased from 20 to 33% (P = 0.001) and from 33 to 37% (P = 0.603). There were 396 (8%) original (FSG = 8.8 mmol/l [159 mg/dl]) and 45 (7%) new (FSG = 10.0 mmol/l [181 mg/dl]) cohort members with diabetes untreated at baseline. Among them, respectively, OHA use reached 38 and 30% and insulin use reached 6 and 16% in 1996-1997. CONCLUSIONS: Diabetes was common in this elderly cohort, and > 80% of treated patients with diabetes at baseline were not achieving fasting glucose goals of < or = 6.7 mmol/l (120 mg/dl). Many untreated at baseline remained untreated after 7 years of follow-up.
Aged↗
Assessment of trans-fatty acid intake with a food frequency questionnaire and validation with adipose tissue levels of trans-fatty acids.
Past studies of the association of trans-fatty acid intake with coronary heart disease have been hindered by the lack of a database on the trans-fatty acid content of various foods. The authors used new data from the US Department of Agriculture to estimate trans-fatty acid intake using a self-administered food frequency questionnaire (FFQ), and they assessed the validity of the FFQ by comparing the dietary estimates with trans-fatty acid concentrations in adipose tissue. The 1996 study included 27 women and 24 men aged 51-78 years. The mean consumption of total trans-fatty acids estimated from the FFQ was 2.24 g per day and 5% of total dietary fat. The mean concentration of total trans-fatty acids in buttock adipose tissue was 4.7% of total fatty acids. Pearson correlations between total dietary intake of trans-fatty acids and total trans-fatty acid levels in adipose tissue were 0.67 (95% confidence interval (CI) 0.36-0.84) among men and 0.58 (95% CI 0.26-0.79) among women. After adjustment for energy intake, age, and body mass index, the correlation coefficients were 0.76 (95% CI 0.51-0.89) among men and 0.52 (95% CI 0.17-0.75) among women. The FFQ validated in this study is an important new tool for assessing usual intake of trans-fatty acids.
Adipose Tissue↗
Diabetes in older adults: comparison of 1997 American Diabetes Association classification of diabetes mellitus with 1985 WHO classification.
BACKGROUND: We aimed to compare the prevalence of abnormal glucose tolerance identified by the 1985 WHO and the 1997 American Diabetes Association (ADA) diagnostic categories based on information collected in the Cardiovascular Health Study, an epidemiological study of elderly people. METHODS: We measured glucose concentrations during fasting and 2 h after a 75 g oral glucose-tolerance test in participants aged 65-100 years in the Cardiovascular Health Study. From a 1989 cohort, we analysed the glucose measurements of 4515 individuals without a previous diagnosis of diabetes and of 262 additional measurements from an African-American cohort recruited in 1992-93. FINDINGS: In the 1989 cohort, the prevalence of untreated diabetes with ADA diagnostic fasting criteria was 7.7% versus a prevalence of 14.8% by the WHO criteria. In the African-American cohort, the prevalence of untreated diabetes was 2.7% with ADA criteria and 11.8% with WHO criteria. 3509 (77.7%) of the 4515 participants in the 1989 cohort had normal glucose concentrations according to ADA fasting criteria, compared with 2401 (53.2%) according to WHO criteria. In the African-American cohort, the corresponding numbers were 239 (91.2%) versus 153 (58.4%). All differences in prevalence of abnormal glucose tolerance between ADA and WHO classifications were significant (p<0.0001). INTERPRETATION: Among elderly individuals, there was a significant difference in the prevalence of diabetes identified by the WHO diagnostic criteria based on oral glucose-tolerance test and the ADA fasting criteria. Consequently, many individuals currently classified as non-diabetic according to ADA criteria would previously have had a diagnosis of diabetes according to WHO criteria. Longitudinal studies are needed to assess the value of the criteria in the identification of individuals at increased risk of diabetes-associated chronic complications.
Black or African American↗
Myocardial infarction and use of low-dose oral contraceptives: a pooled analysis of 2 US studies.
BACKGROUND: Population-based case-control studies to assess the relationship of low-dose oral contraceptive (OC) use with myocardial infarction (MI) were performed at 2 sites in the United States (California and Washington state). The purpose of the present study was to estimate risk of MI in relation to use of low-dose OCs in a pooled analysis combining results from the 2 sites. METHODS AND RESULTS: The study included as cases women aged 18 to 44 years with incident MI who had no prior history of ischemic heart disease or cerebrovascular disease. Women in the case and control groups were interviewed in person regarding OC use and cardiovascular risk factors. The analysis included 271 MI cases and 993 controls. Compared with noncurrent users, the adjusted pooled odds ratio for MI in current OC users was 0.94 (95% CI, 0.44, 2.20) after adjustment for major risk factors and sociodemographic factors. Compared with never users, the adjusted pooled odds ratio for MI was 0.56 (0.21, 1.49) in current OC users and 0.54 (0.31, 0.95) in past OC users. Among past OC users, duration and recency of use were unrelated to MI risk as was current hormone replacement therapy. There was no evidence of interaction between OC use and age, presence of cardiovascular risk factors (hypercholesterolemia, hypertension, diabetes), obesity, or smoking. CONCLUSIONS: We conclude that low-dose OCs as used in these populations are safe with respect to risk of MI in women.
Adolescent↗
Time trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study.
OBJECTIVES: To describe recent temporal patterns of cholesterol-lowering medication use and the characteristics that may have influenced the initiation of cholesterol-lowering therapy among those aged 65 years or older. SUBJECTS AND METHODS: A cohort of 5201 adults 65 years or older were examined annually between June 1989 and May 1996. We added 687 African American adults to the cohort in 1992-1993. We measured blood lipid levels at baseline and for the original cohort in the third year of follow-up. We assessed the use of cholesterol-lowering drugs at each visit. RESULTS: The prevalence of cholesterol-lowering drug use in 1989-1990 was 4.5% among the men and 5.9% among the women; these figures increased over the next 6 years to 8.1% and 10.0%, respectively, in 1995-1996. There was a 4-fold increase in the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors during the 6 years of follow-up, from 1.9% of all participants in 1989-1990 to 7.5% in 1995-1996. The use of bile acid sequestrants, nicotinic acid, and probucol declined from initial levels of less than 1% each. Among the participants who were untreated in 1989-1990, but eligible for cholesterol-lowering therapy after a trial of dietary therapy according to the 1993 guidelines of the National Cholesterol Education Panel, less than 20% initiated drug therapy in the 6 years of follow-up, even among subjects with a history of coronary heart disease. Among participants untreated at baseline but eligible for either cholesterol-lowering therapy or dietary therapy, initiation of cholesterol-lowering drug therapy was directly associated with total cholesterol levels, hypertension, and a history of coronary heart disease, and was inversely related to age, high-density lipoprotein cholesterol levels, and difficulties with activities of daily living. Other characteristics that form the basis of the 1993 National Cholesterol Education Panel guidelines-diabetes, smoking, family history of premature coronary heart disease, and total number of risk factors-were not associated with the initiation of cholesterol-lowering drug therapy. CONCLUSIONS: Given the clinical trial evidence for benefit, those aged 65 to 75 years and with prior coronary heart disease appeared undertreated with cholesterol-lowering drug therapy.
Aged↗
Temporal patterns in the medical treatment of congestive heart failure with angiotensin-converting enzyme inhibitors in older adults, 1989 through 1995.
BACKGROUND: Evidence from clinical trials in the past decade has consistently shown that angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with congestive heart failure (CHF). The extent to which clinical practice has adopted ACE inhibitor therapy is unknown. METHODS: The Cardiovascular Health Study is a prospective observational study of 5201 community-dwelling adults aged 65 years and older. Prevalent CHF cases were identified on study entry (from June 10, 1989, through May 31, 1990) and incident CHF cases were identified throughout 5 years of follow-up. Medication data were collected from annual medication inventories. The percentage of patients with CHF using ACE inhibitors was calculated at each annual examination. Temporal trends in CHF treatment with ACE inhibitors between June 10, 1989, through May 31, 1990, and June 1, 1994, through May 31, 1995, were analyzed. RESULTS: Use of ACE inhibitors to treat CHF increased slightly over time among prevalent cases at each annual examination: 26% of prevalent CHF cases were treated in 1989-1990 compared with 36% of prevalent cases in 1994-1995. This 10% increase was statistically significant (P<.01). Participants with low ejection fractions were 2 times more likely to be treated with ACE inhibitors than were those with normal ejection fraction and this tendency did not change over time. Among cases newly diagnosed in the year before the 1990-1991 examination, 42% were using ACE inhibitors; among those newly diagnosed in the year before 1994-1995, 40% were using ACE inhibitors. This 2% decrease was not statistically significant (P=.68). CONCLUSION: These findings suggest that, while the medical management of CHF with ACE inhibitors has increased modestly over time in prevalent cases, these drugs may still be underused, especially among incident cases.
Aged↗
Time to act on drug safety.
Explore the source record for details and available documents.
Drug Industry↗
Treatment of hypertensive patients with diabetes.
Explore the source record for details and available documents.
Amlodipine↗
Family history as a risk factor for primary cardiac arrest.
BACKGROUND: The hypothesis that a family history of myocardial infarction (MI) or primary cardiac arrest (PCA) is an independent risk factor for primary cardiac arrest was examined in a population-based case-control study. In addition, we investigated whether recognized risk factors account for the familial aggregation of these cardiovascular events. METHODS AND RESULTS: PCA cases, 25 to 74 years old, attended by paramedics during the period 1988 to 1994 and population-based control subjects matched for age and sex were identified from the community by random digit dialing. All subjects were free of recognized clinical heart disease and major comorbidity. A detailed history of MI and PCA in first-degree relatives was collected in interviews with the spouses of case and control subjects by trained interviewers using a standardized questionnaire. For each familial relationship, there was a higher rate of MI or primary cardiac arrest (MI/PCA) in relatives of case compared with relatives of control subjects. Overall, the rate of MI/PCA among first-degree relatives of cardiac arrest patients was almost 50% higher than that in first-degree relatives of control subjects (rate ratio [RR]=1.46; 95% CI=1.23 to 1.72). In a multivariate logistic model, family history of MI/PCA was associated with PCA (RR=1.57; 95% CI=1.27 to 1.95) even after adjustment for other common risk factors. CONCLUSIONS: Family history of MI or PCA is positively associated with the risk of primary cardiac arrest. This association is mostly independent of familial aggregation of other common risk factors.
Aged↗
Norplant implants and cardiovascular disease.
A 1995 publication on serious adverse events in users of Norplant implants submitted to the Food and Drug Administration's MedWatch Spontaneous Reporting System reported 14 hospitalizations for stroke in Norplant users. This number was higher than expected. This is a report on the association of current use of Norplant implants with stroke and myocardial infarction (MI) based on a pooled analysis of data from two population-based, case-control studies conducted in the US. All data collection for these two studies occurred after approval of Norplant implants for marketing in the US in December 1990. The methods of the individual studies are detailed in prior publications.
Adult↗
Health outcomes associated with beta-blocker and diltiazem treatment of unstable angina.
OBJECTIVE: We compared long-term health outcomes associated with beta-adrenergic blocking agents and diltiazem treatment for unstable angina. BACKGROUND: No long-term data have been published comparing these two antianginal treatments in this setting. METHODS: Eligible veterans were discharged from the Veterans Affairs Puget Sound Health Care System (VAPSHCS), Seattle Division, between October 1989 and September 1995 with an unstable angina diagnosis and were prescribed monotherapy beta-blocker or diltiazem treatment at discharge. Medication data were collected from medical records and computerized VAPSHCS outpatient pharmacy files. Follow-up death and coronary artery disease rehospitalization data were collected through 1996. Proportional hazards regression compared survival among diltiazem and beta-blocker users, controlling for patient characteristics with propensity scores. RESULTS: Two hundred forty-seven veterans (24% on beta-blockers, 76% on diltiazem) were included in this study. There were 54 (22%) deaths during an average follow-up of 51 months. After propensity score adjustment, there was no difference in risk of death comparing diltiazem to beta-blocker treatment (hazards ratios [HR] 1.1; 95% confidence interval [CI] 0.49 to 2.4). Among Washington residents (n=207), there were 146 (71%) coronary artery disease rehospitalizations or deaths during follow-up. After adjustment, there was a nonsignificant increase in risk of rehospitalization or death associated with diltiazem use (HR 1.4; 95% CI 0.80 to 2.4). For both analyses, similar risks were found among veterans without relative contraindications to beta-blockers. CONCLUSIONS: We found no survival benefit of diltiazem over beta-blocker treatment for unstable angina in this cohort of veterans.
Adrenergic beta-Antagonists↗
Cost-minimization and the number needed to treat in uncomplicated hypertension.
The goal of this study was to compare the direct costs associated with the prescription of thiazide diuretics, beta-receptor blockers (beta-blockers), angiotensin converting enzyme inhibitors (ACEI), a-receptor blockers (alpha-blockers), and calcium channel blockers (CCB) for the prevention of stroke, myocardial infarction (MI) and premature death in uncomplicated hypertension. We performed a cost-minimization analysis based on numbers-needed-to-treat (NNT) derived from the metaanalysis of 15 major clinical trials of hypertension treatment, and the average wholesale prices of both the most commonly prescribed and the least expensive drugs in each class. The inclusion criteria for clinical trials were that they be randomized, controlled trials of drug therapy of uncomplicated mild-to-moderate hypertension with stroke, MI, or death as endpoints. The wholesale drug costs and the total direct outpatient treatment costs to prevent a stroke, MI or death among middle-aged and elderly hypertensives were our outcome measures. The estimated wholesale drug acquisition cost to prevent one major event (MI or stroke or death) ranged from $4730 to $346,236 among middle-aged patients, and from $1595 to $116,754 in the elderly; generic diuretic or beta-blocker therapy was more economical than treatment with an ACEI, alpha-blocker, or CCB. The associated 5-year NNT was 86 for middle-aged patients and 29 for elderly patients. Diuretic therapy remained more cost-effective even under the unlikely assumption that the newer drugs were 50% more effective than diuretics at preventing these major events. The costs associated with potassium supplementation did not eliminate the advantage of diuretics. Treatment costs to prevent major hypertensive complications are much lower with diuretics and beta-blockers than with ACEI, CCB, or alpha-blockers, especially in middle-aged patients.
Antihypertensive Agents↗