0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Traditional Risk Factors and Subclinical Disease Measures as Predictors of First Myocardial Infarction in Older Adults:  The Cardiovascular Health Study FREE

Bruce M. Psaty, MD, PhD; Curt D. Furberg, MD, PhD; Lewis H. Kuller, MD, DrPH; Diane E. Bild, MD, MPH; Pentti M. Rautaharju, MD, PhD; Joseph F. Polak, MD, MPH; Edwin Bovill, MD; John S. Gottdiener, MD
[+] Author Affiliations

From the Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Wash (Dr Psaty); Department of Public Health Sciences, Bowman Gray School of Medicine, Winston-Salem, NC (Drs Furberg and Rautaharju); Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pa (Dr Kuller); Epidemiology and Biometry Program, Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Bild); Department of Radiology, Brigham and Women's Hospital, Boston, Mass (Dr Polak); Department of Pathology, University of Vermont, Colchester (Dr Bovill); Division of Cardiology, Georgetown University Medical Center, Washington, DC (Dr Gottdiener). A list of participating institutions and principal staff of the Cardiovascular Health Study appears at the end of the article.


Arch Intern Med. 1999;159(12):1339-1347. doi:10.1001/archinte.159.12.1339.
Text Size: A A A
Published online

Background  Risk factors for myocardial infarction (MI) have not been well characterized in older adults, and in estimating risk, we sought to assess the individual and joint contributions made by both traditional risk factors and measures of subclinical disease.

Methods  In the Cardiovascular Health Study, we recruited 5888 adults aged 65 years and older from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination that included traditional risk factors such as blood pressure and fasting glucose level and measures of subclinical disease as assessed by electrocardiography, carotid ultrasonography, echocardiography, pulmonary function, and ankle-arm index. Participants were followed up with semiannual contacts, and all cardiovascular events were classified by the Morbidity and Mortality Committee. The main analytic technique was the Cox proportional hazards model.

Results  At baseline, 1967 men and 2979 women had no history of an MI. After follow-up for an average of 4.8 years, there were 302 coronary events, which included 263 patients with MI and 39 with definite fatal coronary disease. The incidence was higher in men (20.7 per 1000 person-years) than women (7.9 per 1000 person-years). In all subjects, the incidence was strongly associated with age, increasing from 7.8 per 1000 person-years in subjects aged 65 to 69 years to 25.6 per 1000 person-years in subjects aged 85 years and older. Glucose level and systolic blood pressure were associated with the incidence of MI, but smoking and lipid measures were not. After adjustment for age and sex, the significant subclinical disease predictors of MI were borderline or abnormal ejection fraction by echocardiography, high levels of intimal-medial thickness of the internal carotid artery, and a low ankle-arm index. Forced vital capacity and electrocardiographic left ventricular mass did not enter the stepwise model. Excluding subjects with clinical cardiovascular diseases such as prior angina or congestive heart failure at baseline had little effect on these results. Risk factors were generally similar in men and women.

Conclusions  After follow-up of 4.8 years, systolic blood pressure, fasting glucose level, and selected subclinical disease measures were important predictors of the incidence of MI in older adults. Uncontrolled high blood pressure may explain about one quarter of the coronary events in this population.

Figures in this Article

IN MIDDLE-AGED adults, the major risk factors for a first myocardial infarction (MI) have been well characterized and include smoking, diabetes, lipid levels, and systolic and diastolic blood pressures.16 Drug treatment of hypertension and hyperlipidemia is known to reduce the risk of first coronary events.7,8 For several major risk factors in older adults, however, both the levels of risk and the benefits of intervention are in general less clearly established. While the benefits of the treatment of high blood pressure are clear,9,10 the risks associated with elevated levels of cholesterol and the potential benefits of therapy in older adults remain controversial.1114

In recent years, advances in technology have also provided physicians with new diagnostic methods. Echocardiography is widely available, and early population-based studies suggested that echocardiographic left ventricular mass was an important predictor of MI.15 Ultrasound examination of the carotid arteries can be used to assess intima-to-media wall thickness (IMT) as a measure of atherosclerosis,16 and in a recent report from the Rotterdam Cohort Study, IMT of the common carotid artery was associated with increased risks of stroke and MI.17 In the assessment of the risk of MI, the individual and joint contributions of these subclinical disease measures and traditional risk factors have not been previously reported in population-based studies of older adults.

The Cardiovascular Health Study (CHS) was designed to assess these risks. In this analysis, we sought to examine the association of incident MI with (1) traditional risk factors after adjustment for demographic factors, (2) subclinical disease measures before and after adjustment for traditional risk factors, and (3) the best overall set of predictors.

SETTING

The CHS is a prospective cohort study of risk factors for coronary heart disease and stroke in men and women aged 65 years and older. In June 1990, 4 Field Centers completed recruitment of 5201 participants. In June 1993, the recruitment of an additional 687 African Americans was completed. Each community sample was obtained from random samples of the Medicare eligibility lists, and those eligible to participate included all persons who were living in the household of each individual sampled from the Health Care Financing Administration lists and who (1) were 65 years or older, (2) were noninstitutionalized, (3) expected to remain in the area for 3 years, and (4) gave informed consent and did not require a proxy respondent. Among those contacted and eligible, 57.3% were enrolled. The CHS design and recruitment experience are described in detail elsewhere.18,19

BASELINE EXAMINATION

The baseline examination consisted of a home interview and a clinic examination. Participants answered standard questionnaires that assessed a variety of risk factors, including smoking, physical activity, and medical history of cardiovascular conditions.18 The self-reported medical conditions such as MI were validated.20 Medications were assessed by inventory at the home interview.21

Participants were asked to come to the clinic examination after a 12-hour overnight fast. Seated blood pressure, electrocardiography, and venipuncture were performed early in the examination as previously described.18 Duplicate measures of supine blood pressure in the right arm and both posterior tibial arteries were assessed by an 8-MHz Doppler probe attached to a stethoscope, and the ratio of systolic blood pressures was used to calculate the ankle-arm index. Anthropomorphic measures included weight and height. Electrocardiograms (ECGs) were read by the ECG Reading Center,22 and ECG left ventricular mass was estimated according to a new algorithm, which included the best predictors of echocardiographic left ventricular mass in the CHS population.23 The forced vital capacity and forced expiratory volume in 1 second were measured with a water-sealed spirometer (Collins Survey II; WE Collins, Braintree, Mass).

Blood samples from the fasting venipuncture were analyzed at the Central Blood Analysis Laboratory for glucose; fibrinogen; factor VII, standardized to the World Health Organization reference materials; and total cholesterol, high-density lipoprotein cholesterol, and triglycerides, standardized according to the Centers for Disease Control and Prevention as previously described.18,24 Low-density lipoprotein cholesterol was calculated according to the Friedewald equation.25

Carotid sonography was performed with sonographic units (Toshiba SSA-270A; Toshiba America Medical Systems, Tustin, Calif). A single longitudinal lateral view with measurements taken at the distal 10 mm of the far wall of the right and left common carotid arteries and 3 views with measurements centered on the site of maximum wall thickening of the proximal right and left internal carotid arteries were recorded and read by the Ultrasound Reading Center.26 The IMT was the average of the discrete maximum separately for both common and both internal carotid arteries. Readers also estimated the maximum degree of luminal stenosis. The echocardiographic examinations included 2-dimensional and Doppler methods performed with the Toshiba SSH-160A sonographic units. The CHS Echocardiography Reading Center27 read M-mode left ventricular wall thicknesses and dimensions. Readers also classified the ejection fraction in qualitative terms as borderline or abnormal.

The examination of the African American cohort in 1992-1993 was largely the same as the baseline examination of the main cohort in 1989-1990. Echocardiographic results were not available at baseline for the African American cohort, and based on the important predictors identified in the main cohort,28 ejection fraction was imputed.2931 In sensitivity analyses, echocardiographic ejection fraction was an important predictor after excluding the African Americans recruited in 1992-1993. To include this subgroup of the cohort, we used the imputed ejection fraction for the African Americans recruited in 1992-1993.

Subjects were excluded from the analysis if (1) they reported an MI prior to entry into CHS; (2) they had on their baseline ECG evidence of a previous MI defined as the presence of major Q waves or the combination of minor Q waves and ST-T wave changes32; or (3) during follow-up, they were found to have had an MI that predated their entry into CHS.33

FOLLOW-UP AND CLASSIFICATION OF EVENTS

Participants were contacted every 6 months, and the contacts alternated between a telephone interview and a clinic examination, which included an ECG. At each contact, participants were asked about cardiovascular events and all hospitalizations. Discharge summaries and diagnoses were obtained for all hospitalizations. For all potential incident cardiovascular events, additional information, including cardiac enzyme determinations and serial ECGs, was collected.

The algorithm for classifying MI, which includes elements of chest pain, cardiac enzyme levels, and serial ECG changes, has been published.33 For participants whose fatal event did not meet the criteria for a definite fatal MI, deaths were classified as definite fatal coronary heart disease if the participants had chest pain within 72 hours of death or had a history of ischemic heart disease. Final classification of all cardiovascular events was determined by the consensus of the members of the Morbidity and Mortality Committee.33 To identify clinically unrecognized events, annual CHS clinic ECGs were read serially by the ECG Reading Center, and the development of new Q waves (major evolution of Q waves or moderate evolution of Q waves with major ST-T wave evolution; NOVACODES C1 and C222) in a patient without an intervening clinically recognized coronary event was counted as a new silent MI.

Events that were judged by the Morbidity and Mortality Committee to be the consequence of a procedure such as surgery or angioplasty were eliminated from this analysis (n=5 for fatal events and n=45 for nonfatal events), and follow-up for these subjects was censored at the time of their procedure-related event. For subjects with an MI during follow-up, event times were computed as the time to the first definite event. For subjects with a silent MI during follow-up, the event times were set to the midpoint between the serial annual ECGs that identified the new Q waves. For subjects without events, censoring times were calculated as according to the last date of follow-up or the date of death.

DEFINITION OF VARIABLES AND STATISTICAL METHODS

Although participants with a prebaseline MI were excluded, some had a history of coronary heart disease, which was defined as a history at baseline of angina, coronary angioplasty, coronary artery bypass surgery, or use of nitroglycerin at baseline. Clinical cardiovascular disease was defined as a history at baseline of coronary disease, congestive heart failure, stroke, or carotid endarterectomy. Several continuous variables were dichotomized: (1) systolic blood pressure less than 140 mm Hg vs 140 mm Hg or greater; (2) fasting glucose level less than 7 mmol/L vs 7 mmol/L or greater (<126 vs ≥126 mg/dL), which is the new recommended definition for diabetes34; (3) ankle-arm index less than 0.9 vs 0.9 or greater; and (4) internal carotid IMT less than 1.79 vs 1.79 mm or greater (80th percentile for subjects without clinical cardiovascular disease at baseline).

We used SPSS-PC software for data analysis.35 Techniques included t tests for continuous variables, χ2 tests for categorical variables, and Cox proportional hazards models for multivariate analysis.36 Population attributable fraction was calculated according to the formula given by Rothman37 and uses information about the prevalence of a risk factor and its relative risk to estimate that risk factor's contribution to disease incidence in the population as a whole. All P values represent 2-sided tests.

APPROACH TO MULTIVARIATE ANALYSIS

The CHS has a large number of potential predictor variables, and in this analysis, we screened a representative sample of risk factors. The variables age, sex, race, and indicator variables for site were included in all models. Based on the initial bivariate screening, we selected a limited number of variables for multivariate analysis and submitted them to stepwise analysis in 2 separate groups. The first group included traditional major risk factors, which were systolic blood pressure, current smoking, fibrinogen level, fasting glucose level, and high-density lipoprotein cholesterol level. The second group included measures of subclinical disease, and for each examination component we selected a single predictor variable. The subclinical disease measures were ankle-arm index, maximum internal carotid IMT, ECG left ventricular mass, echocardiographic ejection fraction, and forced vital capacity. Data on left ventricular mass as assessed by echocardiography were missing for about one third of subjects, so we chose ECG left ventricular mass instead.23 Criteria for entry and exit in the stepwise models were P<.05 and P>.10, respectively.

Excluded from this analysis were 403 men and 297 women who reported at baseline a previous history of MI; 97 men and 104 women with evidence of an MI on their baseline ECG; and 28 men and 13 women who, during follow-up, were found to have an MI that predated their entry into the CHS. Of 5888 participants, the 1967 men and 2979 women who were at risk of a first MI were included in this analysis and followed up for an average of 4.8 years.

Among all events (Table 1), 29 (9.6%) of 302 were definite fatal MIs, and 39 (12.9%) represented definite fatal coronary heart disease. Another 40 (13.2%) MIs were detected only by the presence of new Q waves on annual in-clinic ECGs. The event rate in men was significantly higher than the rate in women (Table 2), and the incidence was strongly associated with age in both men and women (P<.01).

Table Graphic Jump LocationTable 1. Types of Coronary Events by Sex
Table Graphic Jump LocationTable 2. Incidence of Myocardial Infarction by Age and Sex per 1000 Person-Years*

Table 3 summarizes the baseline risk factors in men and women with and without clinical cardiovascular disease at baseline. In men and women, risk factors such as blood pressure and glucose level were generally higher in subjects with clinical cardiovascular disease. Lipid levels were similar in the 2 groups. The prevalence of smoking was actually lower in those with clinical cardiovascular disease at baseline. The subclinical disease measures, including ejection fraction, carotid IMT, and ankle-arm index, differed between those with and without clinical cardiovascular disease at baseline.

Table Graphic Jump LocationTable 3. Characteristics of Participants Stratified by Sex and Cardiovascular Disease (CVD) Status at Baseline*

Table 4 summarizes the bivariate associations between the incidence of MI and the risk factors that were considered for multivariate analysis. The unadjusted associations for many of the variables were strong and highly significant. With the exception of smoking, glucose level, and forced vital capacity, adjustment for age, sex, and clinical heart disease tended to reduce the strength of the associations.

Table Graphic Jump LocationTable 4. Associations Between the Incidence of Myocardial Infarctions and the Risk Factors Considered for Multivariate Analysis*

Table 5 summarizes the findings for traditional risk factors. After adjustment for age, sex, race, site, and clinical cardiovascular disease, the stepwise model included systolic blood pressure and fasting glucose level. The risk for current smoking was marginal (risk ratio, 1.41; 95% confidence interval, 0.99-2.00; P=.06). In analyses stratified on sex, the point estimates for the risk factors were similar in men and women. Table 6 summarizes the findings for subclinical disease measures after adjustment for demographic factors and traditional risk factors. Three variables—echocardiographic ejection fraction, ankle-arm index, and internal carotid IMT—entered the stepwise model. While internal carotid IMT was a significant predictor in both men and women, echocardiographic ejection fraction was a significant predictor only in women, and ankle-arm index only in men.

Table Graphic Jump LocationTable 5. Multivariate Analysis of Conventional Risk Factors for Myocardial Infarction*
Table Graphic Jump LocationTable 6. Multivariate Analysis of Subclinical Disease Risk Factors for Myocardial Infarction After Adjustment for Demographic Factors and Conventional Risk Factors*

Since the forced entry of all the traditional risk factors into the model in Table 6 may represent overadjustment, we repeated the analysis of subclinical disease measures after adjustment only for age, sex, race, site, and clinical cardiovascular disease (Table 7). Forced vital capacity and ECG left ventricular mass still did not enter the stepwise model. Ankle-arm index was primarily a predictor in participants who did not have clinical cardiovascular disease at baseline.

Table Graphic Jump LocationTable 7. Multivariate Analysis of Subclinical Disease Risk Factors for Myocardial Infarction After Adjustment for Demographic Factors*

In Table 8, we restricted the analysis to subjects without clinical cardiovascular disease at baseline. In this analysis, we adjusted for age, sex, race, and site, and permitted the traditional and subclinical disease measures to compete for entry into the stepwise model. Among all subjects, the significant predictors were the same—systolic blood pressure, fasting glucose level, ankle-arm index, echocardiographic ejection fraction, and internal carotid IMT. With the exception of ejection fraction, the point estimates for these risk factors were similar in men and women. In sex-specific stepwise models, systolic blood pressure, glucose level, ankle-arm index, and internal carotid IMT entered for men; and for women, systolic blood pressure, echocardiographic ejection fraction, and ankle-arm index.

Table Graphic Jump LocationTable 8. Multivariate Analysis of Subclinical Disease and Conventional Risk Factors for Myocardial Infarction Among Subjects Free of Clinical Cardiovascular Disease at Baseline*

Figure 1 provides estimates of the population attribution fraction for these 5 predictors of MI among subjects free of clinical cardiovascular disease at baseline. Continuous variables were dichotomized. The range of prevalences was wide, from 5.2% for abnormal ejection fraction up to 39.5% for elevated systolic blood pressure. The population attributable fractions were highest for the traditional risk factors of elevated systolic blood pressure (24.0%) and fasting glucose level (12.8%). For each of the 3 subclinical disease measures, the population attributable fractions were less than 10%.

Place holder to copy figure label and caption

Population attributable fractions for 5 major risk factors among subjects free of clinical cardiovascular disease at baseline. SBP indicates systolic blood pressure; AAI, ankle-arm index; IC IMT, intima-to-media wall thickness of the internal carotid artery; and echo EF, echocardiographic ejection fraction.

Graphic Jump Location

In additional analysis, results were similar when we excluded the African American cohort recruited in 1992-1993. Systolic blood pressure was much more strongly associated with the incidence of MI than diastolic blood pressure, and after adjustment for systolic blood pressure, there was no association with diastolic blood pressure. None of the lipid measures (total, high-density lipoprotein, and low-density lipoprotein cholesterol or triglycerides) was associated with the risk of MI in this population. In the CHS, the maximum IMT of the internal but not the common carotid artery was associated with the incidence of MI. Analysis using quintiles for systolic blood pressure, ankle-arm index, and carotid IMT suggested generally linear trends in risk for these continuous variables while the elevated risk associated with glucose level was largely confined to those in the highest quintile (glucose level >6.3 mmol/L [>114 mg/dL]). There was no significant interaction between glucose level and drug treatment for diabetes (P=.79) or between systolic blood pressure and drug treatment for hypertension (P=.31). Excluding definite fatal coronary heart disease and excluding silent MI by annual ECG had little effect on the predictors or their estimated risk ratios.

During an average of 4.8 years of follow-up, we identified a first coronary event in 302 (6.1%) of 4946 older adults. The incidence was strongly associated with age, sex, and the presence of other clinical cardiovascular disease. Traditional risk factors, including systolic blood pressure and fasting glucose level, were strongly associated with the incidence of MI in this analysis. The results for smoking were marginal, and there was no association with lipid levels. Several measures of subclinical disease were also important predictors. Internal carotid IMT, ankle-arm index, and echocardiographic ejection fraction were associated with the incidence of MI. In this analysis, forced vital capacity and ECG left ventricular mass did not enter the stepwise models although they were associated with MI in bivariate analyses.

In the CHS, the age-sex specific incidences of MI were 16.3 and 5.8 per 1000 person-years in men and women, respectively, aged 65 to 74 years at baseline and 28.7 and 12.9 in men and women aged 75 to 84 years at baseline. These rates are similar to those reported from 30 years of follow-up (through 1978) in the Framingham Heart Study.6 For the end point of coronary heart disease without angina,6 the respective age-sex specific incidences from Framingham were 18 and 8 per 1000 person-years in men and women aged 65 to 74 years and 27 and 14 in men and women aged 75 to 84 years. While mortality from coronary heart disease has declined precipitously in the past 30 years, the incidence in older adults appears to have changed little. The CHS findings of a relatively high incidence of coronary disease in older adults is consistent with the findings from other studies.38,39 In the Minnesota Heart Survey,39 mortality from coronary disease declined much more dramatically than the occurrence of hospitalizations. Both the improvements in medical care and the detection of less severe events in recent years may be responsible for these trends. Nonetheless, 13.2% of coronary events in the CHS remained clinically silent, detected only as Q wave changes on annual in-clinic ECGs.

In general, the findings from the CHS for traditional risk factors are consistent with those of many previous studies. Although smoking was only marginally significant after adjustment for age, sex, race, clinical cardiovascular disease, systolic blood pressure, and fasting glucose level, the point estimate of a 41% increase in risk is consistent with estimates of other studies that have examined the effect of smoking in older adults.4042 In the CHS, both systolic blood pressure and glucose level were strongly associated with the incidence of MI in older adults. Diabetes is a well-known risk factor in middle-aged adults,43,44 and several recent studies have given us a new appreciation for the importance of diabetes as a risk factor for ischemic heart disease in older adults.45,46 In older adults, systolic blood pressure is a major risk factor for coronary disease,9,47,48 and the data from the CHS suggest that even mild elevations above 140 mm Hg—an elevation present in about 40% of the population—may be important.

There was little association between the incidence of coronary disease and plasma lipid levels in the CHS. Follow-up was relatively short in the CHS, and there is some evidence that the strength of the association between cholesterol level and risk increases with longer follow-up.49 While the level of risk appears to be smaller in the elderly than in the middle-aged, the general consensus seems to be that lipid levels are a risk factor for coronary disease in older adults.4,1114,46

In this analysis, a number of measures of subclinical disease were also associated with the incidence of coronary disease in older adults. Internal carotid IMT, borderline or abnormal echocardiographic ejection fraction, and low ankle-arm index were all independently associated with coronary disease in the CHS cohort even after adjustment for demographic factors, systolic blood pressure, and fasting glucose level. It is interesting to speculate that since ejection fraction is depressed prior to infarction in some subjects, ischemic hibernation may antedate myocardial necrosis.

The findings for subclinical disease are similar to the results of other studies. Low ankle-arm index is a strong predictor of mortality in older adults.50 In the Kuopio Ischemic Heart Disease Risk Factor Study,51 intimal-medial thickening of the common carotid artery was associated with a 2-fold increase in the risk of coronary heart disease. In the Atherosclerosis Risk in Communities Study, Chambless and colleagues52 also reported a strong graded association between carotid IMT and the incidence of coronary heart disease. Although echocardiographic left ventricular mass was also a risk factor in the Framingham Heart Study,15 ECG left ventricular mass was not an independent risk factor in this analysis from CHS. Forced vital capacity was an important predictor in Framingham,53 but did not enter the stepwise models in this analysis.

At the outset, we identified a limited number of candidate variables, and by doing so, we did not examine the association between the incidence of MI and a large number of other variables that may be important predictors. Moreover, in stepwise analysis, the entry of additional variables and the estimates of their relative risks depend importantly on the variables that are already in the model.

The CHS is a population-based study, and 57.3% of eligible subjects enrolled in the CHS. Population attributable fractions depend on estimates of both prevalence and risk level. The prevalences of hypertension and diabetes were actually lower in those who were eligible and enrolled than in those who were eligible but did not enroll.19 If, as seems likely, the associations of risk factors and disease incidence are similar between the enrolled and the unenrolled, the population attributable fractions for these risk factors in the CHS may be slightly underestimated.

Compared with the measurement of blood pressure or fasting glucose, the subclinical disease measures represent more costly high-technology methods of assessing risk. Some of them, including echocardiographic ejection fraction and internal carotid maximum IMT, were important independent risk factors for coronary disease in this study, and clearly their use significantly improved the ability to predict coronary events in older adults. For the clinician seeing patients who have multiple risk factors, including those risk factors defined by subclinical disease measures, it is important to emphasize that these patients have high rates of coronary events.54,55 From the point of screening populations, however, these high-risk patients are uncommon. Among subjects without clinical cardiovascular disease at baseline, the prevalences of low ankle-arm index and borderline or abnormal ejection fraction were relatively low, found in only 9.5% and 5.2.% of the population at baseline, respectively (Figure 1).

In this population, elevated levels of blood pressure and glucose clearly pose the greatest hazard to the health of the public ( Figure 1). Systolic blood pressure elevated above 140 mm Hg may explain one quarter of the coronary events in this study. For stroke in older adults, elevated systolic blood pressure may explain about one third of cerebrovascular events.31 While the health effects of the aggressive treatment of elevated glucose levels in patients with type 2 diabetes are currently under study,56 the effectiveness of antihypertensive therapy, especially low-dose diuretic therapy, is well established in older adults.7 The absolute risk reductions associated with the low-dose diuretic therapy to treat elevated systolic pressure are twice as high in diabetic as in nondiabetic individuals.57 Both in terms of the levels of risk and the prevalence of the conditions, the treatment of even modest levels of systolic hypertension and the prevention of glucose intolerance with diet and physical activity are likely to have the largest effects in preventing the incidence of coronary disease in older adults.

Accepted for publication September 29, 1998.

This research was supported by contracts N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, and N01-HC-85086 from the National Heart, Lung, and Blood Institute, and from the NWO (Nederlandse Organisatie voor Wetenschappelijk Onderzoek). Dr Psaty is a Merck/SER Clinical Epidemiology Fellow (sponsored by the Merck Co Foundation, Rahway, NJ, and the Society for Epidemiologic Research, Baltimore, Md).

We appreciate the comments, criticisms, and suggestions that Teri Manolio, MD, MHS, provided on earlier drafts of the manuscript.

Reprints: Cardiovascular Health Study, Coordinating Center, Century Square, Suite 2105, 1501 Fourth Ave, Seattle, WA 98101.

Participating Institutions and Principal Staff

Field Center in Forsyth County, North Carolina: Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC: Gregory L. Burke, Alan Elster, Walter H. Ettinger, Curt D. Furberg, Edward Haponik, Gerardo Heiss, Dalane Kitzman, H. Sidney Klopfenstein, Margie Lamb, David S. Lefkowitz, Mary F. Lyles, Cathy Nunn, Ward Riley, Maurice Mittelmark, Grethe S. Tell, James F. Toole, Beverly Tucker; Bowman Gray School of Medicine–ECG Reading Center: Farida Rautaharju, Pentti Rautaharju. Field Center in Sacramento County, California: University of California, Davis: William Bommer, Charles Bernick, Andrew Duxbury, Mary Haan, Calvin Hirsch, Paul Kellerman, Lawrence Laslett, Marshall Lee, Virginia Poirier, John Robbins, Marc Schenker, Nemat Borhani. Field Center in Washington County, Maryland: The Johns Hopkins University, Baltimore, Md: M. Jan Busby-Whitehead, Joyce Chabot, George W. Comstock, Linda P. Fried, Joel G. Hill, Steven J. Kittner, Shiriki Kumanyika, David Levine, Joao A. Lima, Neil R. Powe, Thomas R. Price, Jeff Williamson, Moyses Szklo, Melvyn Tockman; MRI Reading Center–The Johns Hopkins University: R. Nick Bryan, Carolyn C. Meltzer, Douglas Fellows, Melanie Hawkins, Patrice Holtz, Michael Kraut, Grace Lee, Larry Schertz, Earl P. Steinberg, Scott Wells, Linda Wilkins, Nancy C. Yue. Field Center in Allegheny County, Pennsylvania:University of Pittsburgh, Pittsburgh, Penn: Diane G. Ives, Charles A. Jungreis, Laurie Knepper, Lewis H. Kuller, Elaine Meilahn, Peg Meyer, Roberta Moyer, Anne Newman, Richard Schulz, Vivienne E. Smith, Sidney K. Wolfson.

Echocardiography Reading Center (Baseline)–University of California, Irvine: Hoda Anton-Culver, Julius M. Gardin, Margaret Knoll, Tom Kurosaki, Nathan Wong; Echocardiography Reading Center (Follow-up)–Georgetown Medical Center, Washington, DC: John Gottdiener, Eva Hausner, Stephen Kraus, Judy Gay, Sue Livengood, Mary Ann Yohe, Retha Webb; Ultrasound Reading Center–Tufts, New England Medical Center, Boston, Mass: Daniel H. O'Leary, Joseph F. Polak, Laurie Funk; Central Blood Analysis Laboratory–University of Vermont, Colchester: Edwin Bovill, Elaine Cornell, Mary Cushman, Russell P. Tracy; Respiratory Sciences–University of Arizona-Tucson: Paul Enright; Coordinating Center–University of Washington, Seattle: Alice Arnold, Annette L. Fitzpatrick, Bonnie K. Lind, Richard A. Kronmal, Bruce M. Psaty, David S. Siscovick, Lynn Shemanski, Lloyd Fisher, Will Longstreth, Patricia W. Wahl, David Yanez, Paula Diehr, Maryann McBurnie; National Heart, Lung, and Blood Institute Project Office: Diane E. Bild, Robin Boineau, Teri A. Manolio, Peter J. Savage, Patricia Smith.

Rosenberg  LPalmer  JRShapiro  S Decline in the risk of myocardial infarction among women who stop smoking. N Engl J Med. 1990;322213- 217
Link to Article
Pan  W-HCedres  LBLiu  KDryer  ASchoenberger  JAShekelle  RB  et al.  Relationship of clinical diabetes and asymptomatic hyperglycemia to risk of coronary heart disease in men and women. Am J Epidemiol. 1986;123504- 516
Iso  HJacobs  DR  JrWentworth  DNeaton  JDCohen  JDMRFIT Research Group, Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the Multiple Risk Factor Intervention Trial. N Engl J Med. 1989;320904- 910
Link to Article
Manolio  TAPearson  TAWenger  NKBarrett-Connor  EPayne  GHHarlan  WR Cholesterol and heart disease in older persons and women: review of NHLBI workshop. Ann Epidemiol. 1992;2161- 176
Link to Article
MacMahon  SPeto  RCutler  J  et al.  Blood pressure, stroke, and coronary heart disease: part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990;335765- 774
Link to Article
Cupples  LAD'Agostino  RB Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Heart Study, 30-year follow-up. Section 34.Kannel  WBWolf  PAGarrison  RJeds.The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease. Bethesda, Md National Institutes of Health1987;NIH publication 87-2703.
Psaty  BMSmith  NSSiscovick  DS  et al.  Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA. 1997;277739- 745
Link to Article
Gould  ALRossouw  JESantanellow  NCHeyse  JFFurberg  CD Cholesterol reduction yields clinical benefit: impact of clinical trials. Circulation. 1998;97946- 952
Link to Article
SHEP Cooperative Research Group, Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;2653255- 3264
Link to Article
Medical Research Council Working Party, Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992;304405- 412
Link to Article
Rubin  SMSidney  SBlack  DMBrowner  WSHulley  SBCummings  SR High blood cholesterol in elderly men and the excess risk for coronary heart disease. Ann Intern Med. 1990;113916- 920
Link to Article
Kronmal  RACain  KCYe  ZOmenn  GS Total serum cholesterol levels and mortality risk as a function of age. Arch Intern Med. 1993;1531065- 1073
Link to Article
Garber  AMBrowner  WS Cholesterol screening guidelines: consensus, evidence and common sense. Circulation. 1997;951642- 1645
Link to Article
Cleeman  JIGrundy  SM National Cholesterol Education Program recommendations for cholesterol testing in young adults: a science-based approach. Circulation. 1997;951646- 1650
Link to Article
Levy  DGarrison  RJSavage  DDKannel  WBCastelli  WP Left ventricular mass and incidence of coronary heart disease in an elderly cohort: the Framingham Heart Study. Ann Intern Med. 1989;110101- 107
Link to Article
O'Leary  DHPolak  JF High-resolution carotid sonography: past, present, and future. AJR Am J Roentgenol. 1989;153699- 704
Link to Article
Bots  MLHoes  AWKoudstaal  PJHofman  AGrobbee  DE Common carotid intima-media thickness and risk of stroke and myocardial infarction: The Rotterdam Study. Circulation. 1997;961432- 1437
Link to Article
Fried  LPBorhani  NOEnright  P  et al.  The Cardiovascular Health Study: design and rationale. Ann Epidemiol. 1991;1263- 276
Link to Article
Tell  GSFried  LPHermanson  BManolio  TANewman  ABBorhani  NO Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. Ann Epidemiol. 1993;3358- 366
Link to Article
Psaty  BMKuller  LHBild  D  et al.  Methods of assessing prevalent cardiovascular disease in the Cardiovascular Health Study. Ann Epidemiol. 1995;5270- 277
Link to Article
Psaty  BMLee  MSavage  PJRutan  GHGerman  PSLyles  M Assessing the use of medications in the elderly: method and initial results in the Cardiovascular Health Study. J Clin Epidemiol. 1992;45683- 692
Link to Article
Rautaharju  PMCalhoun  HPChaitman  BR NOVACODE serial ECG classification system for clinical trials and epidemiologic studies. J Electrocardiol. 1992;24(suppl)179- 187
Link to Article
Rautaharju  PMManolio  TASiscovick  D  et al.  The utility of new electrocardiographic models for left ventricular mass in older adults: the Cardiovascular Health Study. Hypertension. 1996;288- 15
Link to Article
Cushman  MCornell  ESHoward  PRBovill  EGTracy  RP Laboratory methods and quality control in the Cardiovascular Health Study. Clin Chem. 1995;41264- 270
Friedewald  WTLevy  RIFredrickson  DS Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of preparative ultracentrifuge. Clin Chem. 1972;18499- 501
O'Leary  DHPolak  JFWolfson  SK  Jr  et al.  The use of sonography to evaluate carotid atherosclerosis in the elderly: the Cardiovascular Health Study. Stroke. 1991;221155- 1163
Link to Article
Gardin  JMWong  NDBommer  W  et al.  Echocardiographic design of a multi-center investigation of free-living elderly subjects: the Cardiovascular Health Study. J Am Soc Echocardiogr. 1992;563- 72
Link to Article
Gardin  JMArnold  AGottdiener  JS  et al.  Clinical correlates of echocardiographic left ventricular mass in the elderly: the Cardiovascular Health Study. Hypertension. 1997;291095- 1103
Link to Article
Rubin  DB Inference and missing data. Biometrika. 1976;63581- 592
Link to Article
Rubin  DBSchenker  N Multiple imputation in health-care databases: an overview and some applications. Stat Med. 1991;10585- 598
Link to Article
Manolio  TAKronmal  RABurke  GLO'Leary  DHPrice  TRCHS Collaborative Research Group, Short-term predictors of incident stroke in older adults: the Cardiovascular Health Study. Stroke. 1996;271479- 1486
Link to Article
Furberg  CDManolio  TAPsaty  BM  et al.  Major electrocardiographic abnormalities in persons aged 65 years and older (the Cardiovascular Health Study). Am J Cardiol. 1992;691329- 1335
Link to Article
Ives  DGFitzpatrick  ALBild  DE  et al.  Surveillance and ascertainment of cardiovascular events: the Cardiovascular Health Study. Ann Epidemiol. 1995;5278- 285
Link to Article
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;201183- 1197
Norusis  MJSPSS Inc, SPSS/PC+ 4.0 Base Manual for the IBM PC/XT/AT and PS/2.  Chicago, Ill SPSS Inc1990;
Cox  DROakes  D Analysis of Survival Data.  London, England Chapman & Hall1984;
Rothman  KJ Modern Epidemiology.  Boston, Mass Little Brown & Co1986;
Goldberg  RJGore  JMAlpert  JSDalen  JE Recent changes in attack and survival rates of acute myocardial infarction (1975 through 1981): the Worchester Heart Attack Study. JAMA. 1986;2552774- 2779
Link to Article
McGovern  PGPankow  JSShahar  E  et al.  Recent trends in acute coronary heart disease: mortality, morbidity, medical care and risk factors. N Engl J Med. 1996;334884- 890
Link to Article
Jajich  CLOstfeld  AMFreeman  DH Smoking and coronary heart disease mortality in the elderly. JAMA. 1984;2522831- 2834
Link to Article
LaCroix  AZLang  JScherr  P  et al.  Smoking and mortality among older men and women in three communities. N Engl J Med. 1991;3241619- 1625
Link to Article
Kannel  WBLarson  M Long-term epidemiologic prediction of coronary disease: the Framingham experience. Cardiology. 1993;82137- 152
Link to Article
Stamler  JVaccaro  ONeaton  JDWentworth  DMultiple Risk Factor Intervention Trial Research Group, Diabetes, other risk factors, and 12-year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16434- 444
Link to Article
Butler  WJOstrander  LDCarman  WJLamphiear  DE Mortality from coronary heart disease in the Tecumseh Study: long-term effect of diabetes mellitus, glucose intolerance, and other risk factors. Am J Epidemiol. 1985;121541- 547
Kleinman  JCDonahue  RPHarris  MIFinucane  FFMadans  JHBrock  DB Mortality among diabetics in a national sample. Am J Epidemiol. 1988;128389- 401
Frost  PHDavis  BRBurlando  AJ  et al. Systolic Hypertension in the Elderly Research Group, Coronary heart disease risk factors in men and women aged 60 years and older: findings from the Systolic Hypertension in the Elderly Program. Circulation. 1996;9426- 34
Link to Article
Harris  TCook  EFKannel  WSchatzkin  AGoldman  L Blood pressure experience and risk of cardiovascular disease in the elderly. Hypertension. 1985;7118- 124
Link to Article
Taylor  JOCornoni-Huntley  JCurb  JDManton  KGOstfeld  AMScherr  PWallace  RB Blood pressure and mortality risk in the elderly. Am J Epidemiol. 1991;134489- 501
Shipley  MJPocock  SJMarmot  MG Does plasma cholesterol concentration predict mortality from coronary heart disease in elderly people? 18 year follow-up in the Whitehall Study. BMJ. 1991;30389- 92
Link to Article
Vogt  MTCauley  JANewman  ABKuller  LHHulley  SB Decreased ankle/arm blood pressure index and mortality in elderly women. JAMA. 1993;270465- 469
Link to Article
Salonen  JTSalonen  R Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb. 1991;111245- 1249
Link to Article
Chambless  LEHeiss  GFolsom  AR  et al.  Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993. Am J Epidemiol. 1997;146483- 494
Link to Article
Kannel  WBBrand  FN Cardiovascular risk factors in the elderly. Andres  RBierman  ELHazzard  WReds.Principles of Geriatric Medicine. New York, NY McGraw Hill1985;104- 119
Kuller  LBorhani  NFurberg  CD  et al.  Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study. Am J Epidemiol. 1994;1391164- 1179
Kuller  LHShemanski  LPsaty  BM  et al.  Subclinical disease as an independent risk factor for cardiovascular disease. Circulation. 1995;92720- 726
Link to Article
Abraira  CColwell  JNuttall  F  et al.  Cardiovascular events and correlates in the Veterans Affairs Diabetes Feasibility Trial. Arch Intern Med. 1997;157181- 188
Link to Article
Curb  JDPressel  SLCutler  JA  et al. Systolic Hypertension in the Elderly Program Cooperative Research Group, Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. JAMA. 1996;2761886- 1892
Link to Article

Figures

Place holder to copy figure label and caption

Population attributable fractions for 5 major risk factors among subjects free of clinical cardiovascular disease at baseline. SBP indicates systolic blood pressure; AAI, ankle-arm index; IC IMT, intima-to-media wall thickness of the internal carotid artery; and echo EF, echocardiographic ejection fraction.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Types of Coronary Events by Sex
Table Graphic Jump LocationTable 2. Incidence of Myocardial Infarction by Age and Sex per 1000 Person-Years*
Table Graphic Jump LocationTable 3. Characteristics of Participants Stratified by Sex and Cardiovascular Disease (CVD) Status at Baseline*
Table Graphic Jump LocationTable 4. Associations Between the Incidence of Myocardial Infarctions and the Risk Factors Considered for Multivariate Analysis*
Table Graphic Jump LocationTable 5. Multivariate Analysis of Conventional Risk Factors for Myocardial Infarction*
Table Graphic Jump LocationTable 6. Multivariate Analysis of Subclinical Disease Risk Factors for Myocardial Infarction After Adjustment for Demographic Factors and Conventional Risk Factors*
Table Graphic Jump LocationTable 7. Multivariate Analysis of Subclinical Disease Risk Factors for Myocardial Infarction After Adjustment for Demographic Factors*
Table Graphic Jump LocationTable 8. Multivariate Analysis of Subclinical Disease and Conventional Risk Factors for Myocardial Infarction Among Subjects Free of Clinical Cardiovascular Disease at Baseline*

References

Rosenberg  LPalmer  JRShapiro  S Decline in the risk of myocardial infarction among women who stop smoking. N Engl J Med. 1990;322213- 217
Link to Article
Pan  W-HCedres  LBLiu  KDryer  ASchoenberger  JAShekelle  RB  et al.  Relationship of clinical diabetes and asymptomatic hyperglycemia to risk of coronary heart disease in men and women. Am J Epidemiol. 1986;123504- 516
Iso  HJacobs  DR  JrWentworth  DNeaton  JDCohen  JDMRFIT Research Group, Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the Multiple Risk Factor Intervention Trial. N Engl J Med. 1989;320904- 910
Link to Article
Manolio  TAPearson  TAWenger  NKBarrett-Connor  EPayne  GHHarlan  WR Cholesterol and heart disease in older persons and women: review of NHLBI workshop. Ann Epidemiol. 1992;2161- 176
Link to Article
MacMahon  SPeto  RCutler  J  et al.  Blood pressure, stroke, and coronary heart disease: part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990;335765- 774
Link to Article
Cupples  LAD'Agostino  RB Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Heart Study, 30-year follow-up. Section 34.Kannel  WBWolf  PAGarrison  RJeds.The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease. Bethesda, Md National Institutes of Health1987;NIH publication 87-2703.
Psaty  BMSmith  NSSiscovick  DS  et al.  Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA. 1997;277739- 745
Link to Article
Gould  ALRossouw  JESantanellow  NCHeyse  JFFurberg  CD Cholesterol reduction yields clinical benefit: impact of clinical trials. Circulation. 1998;97946- 952
Link to Article
SHEP Cooperative Research Group, Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;2653255- 3264
Link to Article
Medical Research Council Working Party, Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992;304405- 412
Link to Article
Rubin  SMSidney  SBlack  DMBrowner  WSHulley  SBCummings  SR High blood cholesterol in elderly men and the excess risk for coronary heart disease. Ann Intern Med. 1990;113916- 920
Link to Article
Kronmal  RACain  KCYe  ZOmenn  GS Total serum cholesterol levels and mortality risk as a function of age. Arch Intern Med. 1993;1531065- 1073
Link to Article
Garber  AMBrowner  WS Cholesterol screening guidelines: consensus, evidence and common sense. Circulation. 1997;951642- 1645
Link to Article
Cleeman  JIGrundy  SM National Cholesterol Education Program recommendations for cholesterol testing in young adults: a science-based approach. Circulation. 1997;951646- 1650
Link to Article
Levy  DGarrison  RJSavage  DDKannel  WBCastelli  WP Left ventricular mass and incidence of coronary heart disease in an elderly cohort: the Framingham Heart Study. Ann Intern Med. 1989;110101- 107
Link to Article
O'Leary  DHPolak  JF High-resolution carotid sonography: past, present, and future. AJR Am J Roentgenol. 1989;153699- 704
Link to Article
Bots  MLHoes  AWKoudstaal  PJHofman  AGrobbee  DE Common carotid intima-media thickness and risk of stroke and myocardial infarction: The Rotterdam Study. Circulation. 1997;961432- 1437
Link to Article
Fried  LPBorhani  NOEnright  P  et al.  The Cardiovascular Health Study: design and rationale. Ann Epidemiol. 1991;1263- 276
Link to Article
Tell  GSFried  LPHermanson  BManolio  TANewman  ABBorhani  NO Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. Ann Epidemiol. 1993;3358- 366
Link to Article
Psaty  BMKuller  LHBild  D  et al.  Methods of assessing prevalent cardiovascular disease in the Cardiovascular Health Study. Ann Epidemiol. 1995;5270- 277
Link to Article
Psaty  BMLee  MSavage  PJRutan  GHGerman  PSLyles  M Assessing the use of medications in the elderly: method and initial results in the Cardiovascular Health Study. J Clin Epidemiol. 1992;45683- 692
Link to Article
Rautaharju  PMCalhoun  HPChaitman  BR NOVACODE serial ECG classification system for clinical trials and epidemiologic studies. J Electrocardiol. 1992;24(suppl)179- 187
Link to Article
Rautaharju  PMManolio  TASiscovick  D  et al.  The utility of new electrocardiographic models for left ventricular mass in older adults: the Cardiovascular Health Study. Hypertension. 1996;288- 15
Link to Article
Cushman  MCornell  ESHoward  PRBovill  EGTracy  RP Laboratory methods and quality control in the Cardiovascular Health Study. Clin Chem. 1995;41264- 270
Friedewald  WTLevy  RIFredrickson  DS Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of preparative ultracentrifuge. Clin Chem. 1972;18499- 501
O'Leary  DHPolak  JFWolfson  SK  Jr  et al.  The use of sonography to evaluate carotid atherosclerosis in the elderly: the Cardiovascular Health Study. Stroke. 1991;221155- 1163
Link to Article
Gardin  JMWong  NDBommer  W  et al.  Echocardiographic design of a multi-center investigation of free-living elderly subjects: the Cardiovascular Health Study. J Am Soc Echocardiogr. 1992;563- 72
Link to Article
Gardin  JMArnold  AGottdiener  JS  et al.  Clinical correlates of echocardiographic left ventricular mass in the elderly: the Cardiovascular Health Study. Hypertension. 1997;291095- 1103
Link to Article
Rubin  DB Inference and missing data. Biometrika. 1976;63581- 592
Link to Article
Rubin  DBSchenker  N Multiple imputation in health-care databases: an overview and some applications. Stat Med. 1991;10585- 598
Link to Article
Manolio  TAKronmal  RABurke  GLO'Leary  DHPrice  TRCHS Collaborative Research Group, Short-term predictors of incident stroke in older adults: the Cardiovascular Health Study. Stroke. 1996;271479- 1486
Link to Article
Furberg  CDManolio  TAPsaty  BM  et al.  Major electrocardiographic abnormalities in persons aged 65 years and older (the Cardiovascular Health Study). Am J Cardiol. 1992;691329- 1335
Link to Article
Ives  DGFitzpatrick  ALBild  DE  et al.  Surveillance and ascertainment of cardiovascular events: the Cardiovascular Health Study. Ann Epidemiol. 1995;5278- 285
Link to Article
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;201183- 1197
Norusis  MJSPSS Inc, SPSS/PC+ 4.0 Base Manual for the IBM PC/XT/AT and PS/2.  Chicago, Ill SPSS Inc1990;
Cox  DROakes  D Analysis of Survival Data.  London, England Chapman & Hall1984;
Rothman  KJ Modern Epidemiology.  Boston, Mass Little Brown & Co1986;
Goldberg  RJGore  JMAlpert  JSDalen  JE Recent changes in attack and survival rates of acute myocardial infarction (1975 through 1981): the Worchester Heart Attack Study. JAMA. 1986;2552774- 2779
Link to Article
McGovern  PGPankow  JSShahar  E  et al.  Recent trends in acute coronary heart disease: mortality, morbidity, medical care and risk factors. N Engl J Med. 1996;334884- 890
Link to Article
Jajich  CLOstfeld  AMFreeman  DH Smoking and coronary heart disease mortality in the elderly. JAMA. 1984;2522831- 2834
Link to Article
LaCroix  AZLang  JScherr  P  et al.  Smoking and mortality among older men and women in three communities. N Engl J Med. 1991;3241619- 1625
Link to Article
Kannel  WBLarson  M Long-term epidemiologic prediction of coronary disease: the Framingham experience. Cardiology. 1993;82137- 152
Link to Article
Stamler  JVaccaro  ONeaton  JDWentworth  DMultiple Risk Factor Intervention Trial Research Group, Diabetes, other risk factors, and 12-year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16434- 444
Link to Article
Butler  WJOstrander  LDCarman  WJLamphiear  DE Mortality from coronary heart disease in the Tecumseh Study: long-term effect of diabetes mellitus, glucose intolerance, and other risk factors. Am J Epidemiol. 1985;121541- 547
Kleinman  JCDonahue  RPHarris  MIFinucane  FFMadans  JHBrock  DB Mortality among diabetics in a national sample. Am J Epidemiol. 1988;128389- 401
Frost  PHDavis  BRBurlando  AJ  et al. Systolic Hypertension in the Elderly Research Group, Coronary heart disease risk factors in men and women aged 60 years and older: findings from the Systolic Hypertension in the Elderly Program. Circulation. 1996;9426- 34
Link to Article
Harris  TCook  EFKannel  WSchatzkin  AGoldman  L Blood pressure experience and risk of cardiovascular disease in the elderly. Hypertension. 1985;7118- 124
Link to Article
Taylor  JOCornoni-Huntley  JCurb  JDManton  KGOstfeld  AMScherr  PWallace  RB Blood pressure and mortality risk in the elderly. Am J Epidemiol. 1991;134489- 501
Shipley  MJPocock  SJMarmot  MG Does plasma cholesterol concentration predict mortality from coronary heart disease in elderly people? 18 year follow-up in the Whitehall Study. BMJ. 1991;30389- 92
Link to Article
Vogt  MTCauley  JANewman  ABKuller  LHHulley  SB Decreased ankle/arm blood pressure index and mortality in elderly women. JAMA. 1993;270465- 469
Link to Article
Salonen  JTSalonen  R Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb. 1991;111245- 1249
Link to Article
Chambless  LEHeiss  GFolsom  AR  et al.  Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993. Am J Epidemiol. 1997;146483- 494
Link to Article
Kannel  WBBrand  FN Cardiovascular risk factors in the elderly. Andres  RBierman  ELHazzard  WReds.Principles of Geriatric Medicine. New York, NY McGraw Hill1985;104- 119
Kuller  LBorhani  NFurberg  CD  et al.  Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study. Am J Epidemiol. 1994;1391164- 1179
Kuller  LHShemanski  LPsaty  BM  et al.  Subclinical disease as an independent risk factor for cardiovascular disease. Circulation. 1995;92720- 726
Link to Article
Abraira  CColwell  JNuttall  F  et al.  Cardiovascular events and correlates in the Veterans Affairs Diabetes Feasibility Trial. Arch Intern Med. 1997;157181- 188
Link to Article
Curb  JDPressel  SLCutler  JA  et al. Systolic Hypertension in the Elderly Program Cooperative Research Group, Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. JAMA. 1996;2761886- 1892
Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 91

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
JAMAevidence.com

Users' Guides to the Medical Literature
Clinical Resolution

Users' Guides to the Medical Literature
Clinical Scenario