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Major Risk Factors as Antecedents of Fatal and Nonfatal Coronary Heart Disease Events
Philip Greenland, MD;
Maria Deloria Knoll, PhD;
Jeremiah Stamler, MD;
James D. Neaton, PhD;
Alan R. Dyer, PhD;
Daniel B. Garside, BS;
Peter W. Wilson, MD
JAMA. 2003;290:891-897.
ABSTRACT
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Context A frequently cited concept is that individual major risk factors for coronary heart disease (CHD) are absent in many patients (perhaps >50%) with CHD. However, prior studies have not systematically evaluated the extent to which CHD patients have previous exposure to at least 1 risk factor, including diabetes, cigarette smoking, or clinically elevated levels of cholesterol or blood pressure.
Objective To determine the frequency of exposure to major CHD risk factors.
Design, Setting, and Participants Three prospective cohort studies were included: the Chicago Heart Association Detection Project in Industry, with a population sample of 35 642 employed men and women aged 18 to 59 years; screenees for the Multiple Risk Factor Intervention Trial, including 347 978 men aged 35 to 57 years; and a population-based sample of 3295 men and women aged 34 to 59 years from the Framingham Heart Study (FHS). Follow-up lasted 21 to 30 years across the studies.
Main Outcome Measures Fatal CHD in all cohorts and nonfatal myocardial infarction (MI) in the FHS, compared by exposure to major CHD risk factors, defined as total cholesterol of at least 240 mg/dL ( 6.22 mmol/L), systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, cigarette smoking, and diabetes. Participants were stratified by sex and age (18-39 vs 40-59 years).
Results For fatal CHD (n = 20 995), exposure to at least 1 clinically elevated major risk factor ranged from 87% to 100%. Among those aged 40 to 59 years at baseline with fatal CHD (n = 19 263), exposure to at least 1 major risk factor ranged from 87% to 94%. For nonfatal MI, prior exposure was documented in 92% (95% CI, 87%-96%) (n = 167) of men aged 40 to 59 years at baseline and in 87% (95% CI, 80%-94%) (n = 94) of women in this age group.
Conclusions Antecedent major CHD risk factor exposures were very common among those who developed CHD, emphasizing the importance of considering all major risk factors in determining CHD risk estimation and in attempting to prevent clinical CHD. These results challenge claims that CHD events commonly occur in persons without exposure to at least 1 major CHD risk factor.
INTRODUCTION
Precursors of coronary heart disease (CHD) have been extensively studied, and causal risk factors have been identified. Among the many risk factor associations that have been described, the best established CHD risk factors are unfavorable levels of blood cholesterol (especially total and low-density lipoprotein cholesterol) and blood pressure, cigarette smoking, diabetes, and adverse dietary habits.1-2 These characteristics have been designated major risk factors for CHD given their relatively high prevalence in CHD-prone populations, causal relations to CHD, dominance in risk prediction over other putative risk factors, and amenability to prevention and control.3-5 Clinical practice guidelines recommend that clinicians focus attention on all major risk factors in attempting to predict and prevent CHD.6-7
Although the major CHD risk factors are widely recognized as the primary causes of CHD, many studies have demonstrated that clinically elevated cholesterol levels, for example, are often absent in persons who develop CHD.8-12 Since elevated cholesterol is regarded as a leading risk factor for CHD, the lack of evidence of exposure to elevated cholesterol levels has been linked with the proposition that a large percentage of CHD, perhaps as much as 50%, is not attributable to major CHD risk factors.11-12 A related concept, also frequently cited, is that CHD often (50% of the time) occurs in the absence of any major risk factor.13-14 If clinical CHD occurs in a large fraction of cases in the absence of prior exposure to any major CHD risk factor, this finding would justify the search for new or currently unrecognized factors accounting for CHD causation.14 Conversely, if prior exposure to major risk factors is more common than many reports have suggested,8-12 the concept that major risk factors are often absent in CHD may be erroneous.
To address the question of how frequently CHD events are preceded by exposure to major CHD risk factors, we assembled data from 3 large prospective US cohorts followed up for 21 to 30 years. We assessed the prevalence and consistency of major risk factor exposures across the 3 studies, which included both sexes and a spectrum of adult ages, and, where available, nonfatal as well as fatal CHD events.
METHODS
Data from 3 cohorts were examined: the Chicago Heart Association Detection Project in Industry (CHA), the screening component of the Multiple Risk Factor Intervention Trial (MRFIT), and the Framingham Heart Study (FHS). Cohorts were selected for these analyses because data on CHD mortality (and nonfatal CHD in the FHS) were available with extensive and complete follow-up and for men and women (in the CHA and the FHS). Analyses reported here encompassed persons aged 18 to 59 years at baseline.
Chicago Heart Association Detection Project in Industry
The CHA cohort enrolled 22 400 men and 17 122 women aged 18 years or older between late 1967 and early 1973. Approximately 10% of participants were black and 87% were non-Hispanic white. All employees at 84 Chicago-area companies and organizations received survey invitations; the response rate was 53%. Research teams trained in standardized methods of data collection performed all measurements. Age, sex, race/ethnicity, education, blood pressure, serum total cholesterol level, smoking status, height, weight, medical history, and current treatment for hypertension and diabetes were collected from each participant only once. Blood pressure was measured as a single supine reading with a standard mercury sphygmomanometer. Serum total cholesterol was measured by the Levine-Zak method.15 Of 36 294 participants aged 18 to 59 years, those missing risk factor data (n = 314) or with prior or current CHD (n = 338) were excluded.
Deaths were ascertained using local procedures, Social Security Administration records, and the National Death Index. Cause of death was coded by trained staff according to the International Classification of Diseases, Eighth Revision. Death due to CHD was defined as codes 410-414. Detailed survey methods and follow-up procedures have been described.4, 15 Information on nonfatal events was not available in this cohort. The analysis is based on up to 30 years of follow-up (through December 31, 1997).
MRFIT Screenees
Screening took place from 1973 to 1975 in 18 US cities for enrollment of men aged 35 to 57 years into MRFIT. Approximately 90% of screenees were non-Hispanic white, 7% black, 2% Hispanic, 1% Asian, and less than 1% Native American or other race/ethnicity. Among 361 662 men screened, 8322 with missing systolic blood pressure data and 5362 with prior hospitalization for myocardial infarction (MI) were excluded. Data presented herein are from the remaining 347 978 men.
Measurements included blood pressure, measured with a standard mercury sphygmomanometer while the patient was seated; serum total cholesterol (determined by 1 of 14 laboratories that met the standardization requirements of the Centers for Disease Control16), smoking status, and history of drug treatment for diabetes. Deaths prior to 1979 were ascertained using Social Security Administration records, followed by use of the National Death Index or National Death Index Plus. Cause of death was determined from the death certificate by a nosologist using the International Classification of Diseases, Ninth Revision, with CHD death defined as codes 410-414 and 429.2. Analyses encompassed 21 to 23 years of follow-up (through December 31, 1996).
Framingham Heart Study
The FHS began in 1948 and involved 5209 noninstitutionalized white men and women from Framingham, Mass, aged 30 to 62 years. Measurements have been repeated in this cohort every 2 years. Multiple baseline measurements were available; to reduce misclassification bias, data from 3 examinations (visits 2-4) were averaged to obtain a mean baseline value for serum cholesterol and blood pressure. Visit 1 data were not used because blood cholesterol was measured in only 61% of participants. Those who reported cigarette use at any visit from 1 to 4 were classified as current smokers. Diabetes was defined as treatment by a physician (insulin therapy or oral hypoglycemic agents), a record of an abnormal glucose tolerance test result, or a casual blood glucose level of at least 150 mg/dL (8.33 mmol/L) on at least 2 examinations (per the method of Nelson17) at or before visit 4. Serum cholesterol was measured by the method of Abell et al.18 Blood pressure was measured using mercury sphygmomanometers in seated participants.19 The second of 3 blood pressure measurements taken at each examination was used for analyses. Age at visit 4 (approximately 6 years after baseline) was used to stratify participants.
Of 3758 people aged 34 to 59 years, persons with missing data on risk factors at all visits from 2 through 4 (n = 20), those with prior or current cardiovascular disease (n = 157 with clinical diagnoses and n = 286 with electrocardiographic abnormalities), and those taking digitalis (n = 9) were excluded. Follow-up (dating from visit 4) was limited to 30 years (through December 31, 1988) for comparability with the CHA cohort. A staff physician panel reviewed all outcome events. Cause of death was determined from death certificates, hospital records, attending physicians, pathologists, medical examiners, and family members. Nonfatal MI was detected using medical history, physical examination at follow-up, hospitalization records, and communication with personal physicians.
Risk Factor Definitions
Presence of a clinically elevated major risk factor was defined as presence of 1 or more of the following: cholesterol level of at least 240 mg/dL (6.22 mmol/L), diastolic blood pressure of at least 90 mm Hg or systolic blood pressure of at least 140 mm Hg, current medication with cholesterol- or blood pressure–lowering drugs (<1% and <8% in all age-sex groups, respectively), current cigarette use, and clinical report of diabetes.
A secondary analysis was performed with risk factor cut points at higher-than-favorable levels for cholesterol (200 mg/dL [5.18 mmol/L]) and blood pressure (diastolic >80 mm Hg or systolic >120 mm Hg). These cut points were selected based on prior analysis showing that men and women aged 18 to 74 years at baseline in 5 large cohorts with none of these risk factors had relative risks of CHD death that were substantially lower (by 80%-90%) than all others in long-term follow-up.20
Outcome Definitions
A CHD event was defined as death due to CHD in the CHA cohort and MRFIT and as death due to CHD or nonfatal MI in the FHS. Participants who did not develop CHD were defined in the CHA cohort and MRFIT as those who did not die during follow-up or who died of causes other than CHD; in the FHS, they were defined as those who did not have fatal CHD or nonfatal MI.
Data Analyses
Men and women were analyzed separately by baseline age group (18-39 vs 40-59 years). The proportion (95% confidence interval [CI]) who had at least 1 risk factor was calculated by outcome (CHD death vs all others [those who did not die or who died of other causes during follow-up] for the CHA and MRFIT, and CHD death and nonfatal MI, separately, vs all others for the FHS) for each stratum within each cohort. The proportion with 2 or more risk factors at higher-than-favorable levels was also calculated, as was the proportion with each single risk factor considered separately. Comparisons of proportions between those with a CHD event and all others were assessed by  2 or Fisher exact test. The normal approximation to the binomial was used to calculate 95% CIs, except where the proportion was 100%, in which case the lower bound was estimated as (0.025)1/n, where n is the sample size.21 Analyses were performed using SAS version 8.02 (SAS Institute Inc, Cary, NC). All P values are 2-sided and significant at P<.05.
RESULTS
Analyses were based on 1798 CHD deaths in the CHA, 18 858 CHD deaths in MRFIT, and 642 CHD events (339 CHD deaths and 303 nonfatal MI events) in the FHS. Deaths due to unknown causes numbered 53 in the CHA, 611 in MRFIT (381 coded as unknown cause on death certificate and 230 with no death certificate), and 97 in the FHS; these deaths were excluded from the analyses. For CHA men aged 18 to 39 years, median time to CHD death was 18.9 years (interquartile range [IQR], 14.5-23.2 years); for men aged 40 to 59 years, it was 16.7 years (IQR, 10.3-22.0 years); for women aged 18 to 39 years, it was 23.5 years (IQR, 21.1-24.9 years); and for women aged 40 to 59 years, it was 19.9 years (IQR, 14.8-23.9 years). For MRFIT, median time to CHD death for men aged 35 to 39 years was 15.4 years (IQR, 10.7-19.0 years) and for men aged 40 to 57 years was 14.2 years (IQR, 9.0-18.4 years). For FHS men aged 34 to 39 years, median time to CHD event was 19.1 years (IQR, 13.0-25.4 years); for men aged 40 to 59 years, it was 17.2 years (IQR, 9.6-23.5 years); for women aged 34 to 39 years, it was 24.4 years (IQR, 20.3-27.6 years); and for women aged 40 to 59, it was 19.3 years (IQR, 13.8-25.2 years).
Presence of 1 or More Clinically Elevated Major CHD Risk Factors at Baseline
Table 1 shows proportions of men and women with at least 1 clinically elevated major risk factor among those who died of CHD: for young adult men, CHA, 95.0%; MRFIT, 88.0%; and FHS, 89.5%; for young adult women, CHA, 92.0% and FHS, 100%; for middle-aged men, CHA, 92.7%; MRFIT, 87.0%; and FHS, 90.1%; and for middle-aged women, CHA, 93.8% and FHS, 90.2%. For nonfatal MI in the FHS, proportions ranged from 69.2% in young adult women to 91.6% in middle-aged men. In strata with 19 or more events, the lowest bound for the 95% CIs was 73%. Lower 95% CI bounds in remaining strata (younger FHS women) were 54% (6 events) for fatal CHD and 43% (13 events) for nonfatal MI.
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Table 1. Men and Women With at Least 1 Clinically Elevated Major CHD Risk Factor by Cohort, CHD Outcome, Sex, and Baseline Age*
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Predictably, prior exposure to at least 1 major risk factor at higher-than-favorable levels (cholesterol 200 mg/dL [5.18 mmol/L], blood pressure >120/80 mm Hg, smoking, or diabetes) was more prevalent than described above (Table 2). Ranges in the proportion exposed among all age-sex groups who experienced CHD death were 96% to 99% (CHA), 98% to 99% (MRFIT), and 99% to 100% (FHS). For nonfatal MI in the FHS, exposure ranged from 85% to 100%. When events were frequent (>19 events), for either fatal or nonfatal CHD, lower bounds for 95% CIs were 82% or higher for this secondary analysis.
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Table 2. Men and Women With at Least 1 Major CHD Risk Factor at Higher-Than-Favorable Levels by Cohort, CHD Outcome, Sex, and Baseline Age*
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Among those who did not experience CHD, exposure to at least 1 risk factor in the clinically elevated range occurred in 58% to 85% (Table 1).
Estimates of the proportions of men and women with 2 or more major risk factors at higher-than-favorable levels at baseline were also substantial, ranging from 64% to 100% for those experiencing fatal CHD and 46% to 88% for those experiencing nonfatal MI (Table 3).
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Table 3. Men and Women With at Least 2 Major CHD Risk Factors at Higher-Than-Favorable Levels by Cohort, CHD Outcome, Sex, and Baseline Age*
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Presence of Individual Risk Factors
Among those who experienced a CHD event, the proportions who had a baseline serum cholesterol level of at least 240 mg/dL (6.22 mmol/L) in both age groups ranged from 16% in younger women for fatal CHD in the CHA cohort to 63% among older FHS women for CHD death. Exposure rates were similar within the FHS for fatal CHD and nonfatal MI (Table 4). Proportions with systolic blood pressure of at least 140 or diastolic blood pressure of at least 90 mm Hg at baseline ranged from 7.7% for nonfatal MI in younger FHS women to more than 70% in older CHA men and women. For men and women in all 3 cohorts who later experienced CHD, smoking was more prevalent in the younger age group (62%-100%) but was also highly prevalent in the older age group (45%-75%).
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Table 4. Men and Women With Individual CHD Risk Factors at Higher-Than-Favorable or Clinically Elevated Levels by Cohort, CHD Outcome, Sex, and Baseline Age*
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Among those who did not develop CHD, individual risk factors at higher-than-optimal levels were less prevalent at baseline but were still common (Table 4).
COMMENT
This study demonstrated a high prevalence of exposure to 1 or more major CHD risk factors before a CHD event. This finding held true whether we used the primary analysis definition of exposure as clinically elevated levels of at least 1 major risk factor (cholesterol 240 mg/dL [6.22 mmol/L], arterial blood pressure 140/90 mm Hg, medication use for hypertension or high cholesterol, cigarette smoking, or clinical diabetes) or the secondary analysis definition of unfavorable cholesterol levels (200 mg/dL [5.18 mmol/L]) or blood pressure levels (>120/80 mm Hg), medication use for hypertension or high cholesterol, current cigarette use, or diabetes. For fatal CHD, in all 3 of these large, long-term prospective cohort studies, prior exposure to at least 1 clinically elevated major CHD risk factor ranged from 87% to 100%. For nonfatal MI in the FHS, in both older men and older women, prior risk factor exposures in the clinically elevated range were 92% and 87%, respectively. In younger FHS participants, estimates were less stable due to a small number of events, but they were still in the range of 69% to 86%.
Results were consistent among the 3 cohorts, in both sexes, and across a range of baseline ages under 60 years. High proportions of CHD events also occurred in persons exposed to 2 or more major CHD risk factors at higher-than-favorable levels (64%-100% for fatal CHD and 46%-88% for nonfatal MI). These results challenge claims in the medical literature that CHD events commonly occur (as often as 50% of the time) in persons who have not been exposed to at least 1 major risk factor.8-12
Although the high prevalence of antecedent CHD risk factor exposures found in the 3 cohorts here may seem unexpected, findings in 2 clinical CHD studies provide support for the high prevalence of major lipid risk factors at higher-than-favorable levels among CHD patients. Specifically, total cholesterol measured in men and women who had developed clinical CHD was at a higher-than-favorable level (200 mg/dL [5.18 mmol/L]) in approximately 75%.22-23 Only 7% of persons with CHD in these 2 studies had desirable levels of 2 major cholesterol fractions (low-density lipoprotein <100 mg/dL [<2.59 mmol/L] and high-density lipoprotein 35 mg/dL [0.91 mmol/L]). To our knowledge, there are no prior reports of the magnitude of exposures to clinically elevated levels of all major CHD risk factors in cohorts followed up over a long term for CHD events.
Unfavorable levels of blood cholesterol and blood pressure, cigarette smoking, overweight/obesity, and diabetes are well established as the major causal factors for CHD.1-7 These 5 factors, along with adverse dietary habits that also promote CHD risk, are highly prevalent in populations with epidemic CHD; for several of these factors, clinical trials have demonstrated lowered CHD event rates when the factor is treated and reduced.2, 6-7
A critically important feature of these risk factors is that each has a continuous, dose-dependent impact on CHD risk. In particular, for cholesterol, blood pressure, smoking, and overweight, higher levels of the risk factors translate into greater CHD risk.3, 6-7,24 Thus, cut points for intervention at clinically elevated levels (eg, hyperlipidemic vs normolipidemic) have been adopted to define a high-risk clinical intervention strategy, but this approach underestimates the true effects of these factors on CHD risk. Because these risk factors have a continuous relationship to risk of CHD, in this study we evaluated 2 different cut points for defining risk factor exposures. Even with application of the higher cut points for cholesterol and blood pressure levels, prior exposure to 1 or more major CHD risk factor in CHD cases was common.
This study also suggested that, in these large US cohorts, exposure to 1 or more of the major CHD risk factors was also highly prevalent among individuals who did not develop clinical CHD during lengthy periods of follow-up. Various explanations for this paradox can be considered. First, the study only dealt with clinically apparent CHD; therefore, we cannot determine how many individuals in each of the 3 cohorts had subclinical CHD following risk factor exposure. In addition, as with most diseases, exposure to the etiologic agents for CHD is necessary but not sufficient to cause the clinical disease in all persons. Host factors, which might include genetic characteristics, environmental exposures, or both, undoubtedly protect certain exposed persons from becoming diseased. High-density lipoprotein cholesterol,2-3 for example, has well-known mitigating effects on CHD risk, even in the presence of adverse levels of major risk factors. Other protective factors are emerging, such as cholesteryl ester transfer protein, which has been reported to have antiatherogenic effects.25 Alternatively, major CHD risk factors are also associated with competing causes of death, such as lung cancer and stroke.
On the basis of our findings and those considered elsewhere by others,13, 20, 24 it is apparent that clinically elevated levels of 1 or more of the major causal CHD risk factors precede a very high proportion of fatal or nonfatal CHD events. Women aged 34 to 39 years at baseline in the FHS did not follow this pattern, and they experienced reduced exposures to major risk factors compared with the other cohorts studied. However, in FHS women in this stratum, only 13 events took place during the 30 years of follow-up, and 95% CIs were wide (43%-95%). Overall, these data indicate that prior estimates of the relative infrequency of major risk factor exposures among CHD cases were probably incorrect.
Several factors may have led to inappropriately low prior estimates of the frequency of major risk factor exposures in CHD. These include effects of regression dilution bias causing underestimation of risk impact in most observational studies26; lag or incubation effect from onset of exposure to development of disease, necessitating an exploration of prior exposures using long-term follow-up, as was feasible in this study27; and inability to recognize or quantify exposures in apparently unexposed groups.24 Another contributing factor is the cumulative effect of major risk factors throughout an individual's life.28 For example, the FHS recently reported that remote antecedent blood pressure predicted cardiovascular disease risk more strongly than proximal blood pressures.29 Accordingly, recent risk factor measurements probably underestimate prevalence and impact of risk factor exposures.
These data underscore the importance of considering all major risk factors in CHD risk estimation and in attempting to prevent clinical CHD. Based on these and related findings concerning the major risk factors,13, 20, 24 we suggest that preventing development of unfavorable levels of blood cholesterol and blood pressure, cigarette smoking, diabetes, and unfavorable body weight (as a precursor of unfavorable blood lipid and blood pressure levels and diabetes) should be given even greater priority than is presently the case. Although blood lipid levels are important major CHD risk factors, a 1-sided focus on cholesterol as the major CHD risk factor11-12,14 cannot be justified. Rather, these data provide an important reminder that attention must be accorded to all major risk factor exposures to address the continuing CHD epidemic.6-7,13, 20
AUTHOR INFORMATION
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Corresponding Author and Reprints: Philip Greenland, MD, 680 N Lake Shore Dr, Suite 1102, Chicago, IL 60611 (e-mail: p-greenland{at}northwestern.edu).
Author Contributions: Study concept and design: Greenland, Stamler, Dyer.
Acquisition of data: Greenland, Knoll, Stamler, Neaton, Garside, Wilson.
Analysis and interpretation of data: Greenland, Knoll, Stamler, Neaton, Dyer, Wilson.
Drafting of the manuscript: Greenland, Knoll, Neaton.
Critical revision of the manuscript for important intellectual content: Knoll, Stamler, Dyer, Garside, Wilson.
Statistical expertise: Knoll, Neaton, Dyer.
Obtained funding: Greenland, Stamler, Neaton, Dyer, Wilson.
Administrative, technical, or material support: Stamler, Garside, Wilson.
Study supervision: Greenland, Stamler.
Funding/Support: The Chicago-based investigators acknowledge support by the American Heart Association and its Chicago and Illinois affiliates; grants R01-HL 15174, R01-HL 21010, and R01-HL 03387 from the National Heart, Lung, and Blood Institute (NHLBI); and the Chicago Health Research Foundation. The FHS and MRFIT studies also have been supported over many years by funding, predominantly from the NHLBI (MRFIT, current NHLBI grant NIH/1R01-HL68140; FHS, current NIH/NHLBI contract NO1-HC-25195).
Acknowledgment: A list of colleagues who contributed to earlier aspects of this work has been published (Cardiology. 1993;82:191-222). In addition, we acknowledge the long-term commitment of numerous FHS and MRFIT investigators who performed the data collection for these analyses.
Author Affiliations: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Ill (Drs Greenland, Knoll, Stamler, and Dyer and Mr Garside); School of Public Health, University of Minnesota, Minneapolis (Dr Neaton); and Boston University School of Medicine, Boston, Mass (Dr Wilson).
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Atherosclerosis Imaging: Prognostically Useful or Merely More of What We Know?
Kaul and Douglas
Circ Cardiovasc Imaging 2009;2:150-160.
FULL TEXT
Heart Disease and Stroke Statistics--2009 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee
WRITING GROUP MEMBERS et al.
Circulation 2009;119:e21-e181.
FULL TEXT
BMI, lipid profile, physical fitness and smoking habits of young male adults and the association with parental education
Stea et al.
Eur J Public Health 2009;19:46-51.
ABSTRACT
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Sleep Duration and Coronary Heart Disease Mortality Among Chinese Adults in Singapore: A Population-based Cohort Study
Shankar et al.
Am J Epidemiol 2008;168:1367-1373.
ABSTRACT
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Von Willebrand Factor, Type 2 Diabetes Mellitus, and Risk of Cardiovascular Disease: The Framingham Offspring Study
Frankel et al.
Circulation 2008;118:2533-2539.
ABSTRACT
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History of coronary heart disease and cognitive performance in midlife: the Whitehall II study
Singh-Manoux et al.
Eur Heart J 2008;29:2100-2107.
ABSTRACT
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Key Issues in the Developing Synergism between Cardiovascular Imaging and Biomarkers
Jaffe
Clin. Chem. 2008;54:1432-1442.
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Primary Prevention of Stroke: Impact of Healthy Lifestyle
Gorelick
Circulation 2008;118:904-906.
FULL TEXT
The Impact of Prevention on Reducing the Burden of Cardiovascular Disease
Kahn et al.
Diabetes Care 2008;31:1686-1696.
ABSTRACT
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Traditional Risk Factors Are Predictive on Segmental Localization of Coronary Artery Disease
Tacoy et al.
ANGIOLOGY 2008;59:402-407.
ABSTRACT
Heart rate: from risk marker to risk factor
Borer
Eur Heart J Suppl 2008;10:F2-F6.
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Heart rate management: a therapeutic goal throughout the cardiovascular continuum
Zamorano
Eur Heart J Suppl 2008;10:F17-F21.
ABSTRACT
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The Impact of Prevention on Reducing the Burden of Cardiovascular Disease
Kahn et al.
Circulation 2008;118:576-585.
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Performance of Comorbidity Measures to Predict Stroke and Death in a Community-Dwelling, Hypertensive Medicaid Population
Tang et al.
Stroke 2008;39:1938-1944.
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Predictors of successful, self-reported lifestyle changes in a defined middle-aged population: The Soderakra Cardiovascular Risk Factor Study, Sweden
Petersson et al.
Scand J Public Health 2008;36:389-396.
ABSTRACT
Adverse Cardiovascular Effects of Acute Salt Loading in Young Normotensive Individuals
Tzemos et al.
Hypertension 2008;51:1525-1530.
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Comparison of Two Point-of-Care Lipid Analyzers for Use in Global Cardiovascular Risk Assessments
Dale et al.
The Annals of Pharmacotherapy 2008;42:633-639.
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Lipid Levels in the Post-Acute Coronary Syndrome Setting: Destabilizing Another Myth?
Miller
J Am Coll Cardiol 2008;51:1446-1447.
FULL TEXT
Preventing Heart Disease in the 21st Century: Implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study
McGill et al.
Circulation 2008;117:1216-1227.
FULL TEXT
Association Between Cardiovascular Risk Profiles and the Presence and Extent of Different Types of Coronary Atherosclerotic Plaque as Detected by Multidetector Computed Tomography
Bamberg et al.
Arterioscler. Thromb. Vasc. Bio. 2008;28:568-574.
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A changing paradigm for prevention of cardiovascular disease: emergence of the metabolic syndrome as a multiplex risk factor
Grundy
Eur Heart J Suppl 2008;10:B16-B23.
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The Role of the Diabetes Educator: Patient Case Scenarios
Haas
The Diabetes Educator 2008;34:32S-36S.
ABSTRACT
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Heart Disease and Stroke Statistics--2008 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Writing Group Members et al.
Circulation 2008;117:e25-e146.
FULL TEXT
Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction
Packard and Libby
Clin. Chem. 2008;54:24-38.
ABSTRACT
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Causation: A loosely founded concept in epidemiology
Glick
Journal of the American Dental Association 2007;138:1532-1533.
FULL TEXT
Time to End the Mixed and Often Incorrect Messages About Prevention and Treatment of Atherosclerotic Cardiovascular Disease
Greenland and Lloyd-Jones
J Am Coll Cardiol 2007;50:2133-2135.
FULL TEXT
A Prospective Study of Cigarette Smoking and Risk of Incident Hypertension in Women
Bowman et al.
J Am Coll Cardiol 2007;50:2085-2092.
ABSTRACT
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Is Phenomenology the Best Approach to Health Research?
Kuller
Am J Epidemiol 2007;166:1109-1115.
ABSTRACT
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Coronary Artery Calcification Progression Is Heritable
Cassidy-Bushrow et al.
Circulation 2007;116:25-31.
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Screening for cardiovascular risk factors in a dental setting
Greenberg et al.
Journal of the American Dental Association 2007;138:798-804.
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Decreased risk of death from coronary heart disease amongst men with higher 'femininity' scores: a general population cohort study
Hunt et al.
Int J Epidemiol 2007;36:612-620.
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Sex Differences in Perceived Risks, Distrust, and Willingness to Participate in Clinical Trials: A Randomized Study of Cardiovascular Prevention Trials
Ding et al.
Arch Intern Med 2007;167:905-912.
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Managing nonalcoholic fatty liver disease: Recommendations for family physicians
Grattagliano et al.
cfp 2007;53:857-863.
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Socioeconomic Position, Co-Occurrence of Behavior-Related Risk Factors, and Coronary Heart Disease: the Finnish Public Sector Study
Kivimaki et al.
Am. J. Public Health 2007;97:874-879.
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Low Risk--and the "No More Than 50%" Myth/Dogma
Stamler
Arch Intern Med 2007;167:537-539.
FULL TEXT
Development and Validation of Improved Algorithms for the Assessment of Global Cardiovascular Risk in Women: The Reynolds Risk Score
Ridker et al.
JAMA 2007;297:611-619.
ABSTRACT
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Heart Disease and Stroke Statistics--2007 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Rosamond et al.
Circulation 2007;115:e69-e171.
FULL TEXT
Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death
Wang et al.
NEJM 2006;355:2631-2639.
ABSTRACT
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Environmental Cardiology: Studying Mechanistic Links Between Pollution and Heart Disease
Bhatnagar
Circ. Res. 2006;99:692-705.
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Prevalence of metabolic syndrome in young patients with acute MI: does the Framingham Risk Score underestimate cardiovascular risk in this population?
Zarich et al.
Diabetes and Vascular Disease Research 2006;3:103-107.
ABSTRACT
New-onset diabetes and risk of all-cause and cardiovascular mortality: the cardiovascular health study.
Smith et al.
Diabetes Care 2006;29:2012-2017.
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Dental and Periodontal Status and Risk for Progression of Carotid Atherosclerosis: The Inflammation and Carotid Artery Risk for Atherosclerosis Study Dental Substudy
Schillinger et al.
Stroke 2006;37:2271-2276.
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Healthy Lifestyle Factors in the Primary Prevention of Coronary Heart Disease Among Men: Benefits Among Users and Nonusers of Lipid-Lowering and Antihypertensive Medications
Chiuve et al.
Circulation 2006;114:160-167.
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The Effect of Including C-Reactive Protein in Cardiovascular Risk Prediction Models for Women
Cook et al.
ANN INTERN MED 2006;145:21-29.
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Comparison of risk factors for cardiovascular mortality in black and white adults.
Carnethon et al.
Arch Intern Med 2006;166:1196-1202.
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A tale of three species rabbits, chickens and humans: an interview with clinical trials pioneer Jeremiah Stamler
Wittes
Clin Trials 2006;3:320-334.
Atherosclerosis imaging of asymptomatic individuals: is the sales cart before the evidence horse?
O'Malley
Arch Intern Med 2006;166:1065-1068.
FULL TEXT
Explaining the social gradient in coronary heart disease: comparing relative and absolute risk approaches
Lynch et al.
J. Epidemiol. Community Health 2006;60:436-441.
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The Relationship Between Plasma Levels of Oxidized and Reduced Thiols and Early Atherosclerosis in Healthy Adults
Ashfaq et al.
J Am Coll Cardiol 2006;47:1005-1011.
ABSTRACT
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Heart Disease and Stroke Statistics--2006 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Thom et al.
Circulation 2006;113:e85-e151.
FULL TEXT
Hypertension, Menopause, and Coronary Artery Disease Risk in the Women's Ischemia Syndrome Evaluation (WISE) Study
Gierach et al.
J Am Coll Cardiol 2006;47:S50-S58.
ABSTRACT
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Midlife Body Mass Index and Hospitalization and Mortality in Older Age
Yan et al.
JAMA 2006;295:190-198.
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Estimating the Proportion of Disease due to Classes of Sufficient Causes
Hoffmann et al.
Am J Epidemiol 2006;163:76-83.
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Joint Effects of Systolic Blood Pressure and Serum Cholesterol on Cardiovascular Disease in the Asia Pacific Region
Asia Pacific Cohort Studies Collaboration
Circulation 2005;112:3384-3390.
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C-Reactive Protein and Risk of Cardiovascular Disease in Men and Women From the Framingham Heart Study
Wilson et al.
Arch Intern Med 2005;165:2473-2478.
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High Attributable Risk of Elevated C-Reactive Protein Level to Conventional Coronary Heart Disease Risk Factors: The Third National Health and Nutrition Examination Survey
Miller et al.
Arch Intern Med 2005;165:2063-2068.
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Identification of the Four Conventional Cardiovascular Disease Risk Factors by Dutch General Practitioners
van Wyk et al.
Chest 2005;128:2521-2527.
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Coronary Calcium Independently Predicts Incident Premature Coronary Heart Disease Over Measured Cardiovascular Risk Factors: Mean Three-Year Outcomes in the Prospective Army Coronary Calcium (PACC) Project
Taylor et al.
J Am Coll Cardiol 2005;46:807-814.
ABSTRACT
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Race/Ethnicity, Income, Major Risk Factors, and Cardiovascular Disease Mortality
Thomas et al.
Am. J. Public Health 2005;95:1417-1423.
ABSTRACT
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Role of Lipoprotein-Associated Phospholipase A2 in Atherosclerosis: Biology, Epidemiology, and Possible Therapeutic Target
Zalewski and Macphee
Arterioscler. Thromb. Vasc. Bio. 2005;25:923-931.
ABSTRACT
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Relative Importance of Borderline and Elevated Levels of Coronary Heart Disease Risk Factors
Vasan et al.
ANN INTERN MED 2005;142:393-402.
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Discovering the Full Spectrum of Cardiovascular Disease: Minority Health Summit 2003: Report of the Outcomes Writing Group
Benjamin et al.
Circulation 2005;111:e124-e133.
FULL TEXT
Hypertension Prevalence, Awareness, Treatment, and Control in an Adult Type 1 Diabetes Population and a Comparable General Population
Maahs et al.
Diabetes Care 2005;28:301-306.
ABSTRACT
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Conditional Risk Factors for Atherosclerosis
Kullo and Ballantyne
Mayo Clin Proc. 2005;80:219-230.
ABSTRACT
Venous Thrombosis: The Role of Genes, Environment, and Behavior
Rosendaal
ASH Education Book 2005;2005:1-12.
ABSTRACT
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Brachial Artery Vasodilator Function and Systemic Inflammation in the Framingham Offspring Study
Vita et al.
Circulation 2004;110:3604-3609.
ABSTRACT
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Today's Agenda: We Must Focus on Achieving Favorable Levels of All Risk Factors Simultaneously
Daviglus and Liu
Arch Intern Med 2004;164:2086-2087.
FULL TEXT
Prevalence of Heart Disease and Stroke Risk Factors in Persons With Prehypertension in the United States, 1999-2000
Greenlund et al.
Arch Intern Med 2004;164:2113-2118.
ABSTRACT
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Update in Cardiology
Bonow
ANN INTERN MED 2004;141:628-634.
FULL TEXT
Lipoprotein-Associated Phospholipase A2 Adds to Risk Prediction of Incident Coronary Events by C-Reactive Protein in Apparently Healthy Middle-Aged Men From the General Population: Results From the 14-Year Follow-Up of a Large Cohort From Southern Germany
Koenig et al.
Circulation 2004;110:1903-1908.
ABSTRACT
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Poor Predictive Value of High-Sensitivity C-Reactive Protein Indicates Need for Reassessment
Levinson et al.
Clin. Chem. 2004;50:1733-1735.
FULL TEXT
C-Reactive Protein as a Screening Test for Cardiovascular Risk in a Multiethnic Population
Anand et al.
Arterioscler. Thromb. Vasc. Bio. 2004;24:1509-1515.
ABSTRACT
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Commentary on "New and Emerging Theories of Cardiovascular Disease"
Wessel et al.
Biol Res Nurs 2004;6:17-20.
Effects of Isolated Isoflavonoids on Lipids, Lipoproteins, Insulin Sensitivity, and Ghrelin in Postmenopausal Women
Nikander et al.
J. Clin. Endocrinol. Metab. 2004;89:3567-3572.
ABSTRACT
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Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events
Ridker et al.
Circulation 2004;109:IV-6-IV-19.
FULL TEXT
Should C-Reactive Protein Be Added to Metabolic Syndrome and to Assessment of Global Cardiovascular Risk?
Ridker et al.
Circulation 2004;109:2818-2825.
ABSTRACT
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Parental Cardiovascular Disease as a Risk Factor for Cardiovascular Disease in Middle-aged Adults: A Prospective Study of Parents and Offspring
Lloyd-Jones et al.
JAMA 2004;291:2204-2211.
ABSTRACT
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Cardiology management improves secondary prevention measures among patients with coronary artery disease
Ho et al.
J Am Coll Cardiol 2004;43:1517-1523.
ABSTRACT
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Plaque characterization: surrogate markers or the real thing?
Wickline
J Am Coll Cardiol 2004;43:1185-1187.
FULL TEXT
Is there a need for novel cardiovascular risk factors?
von Eckardstein
Nephrol Dial Transplant 2004;19:761-765.
FULL TEXT
Traditional Risk Factors for Coronary Heart Disease
Rockhill
JAMA 2004;291:299-299.
FULL TEXT
Traditional Risk Factors for Coronary Heart Disease--Reply
Khot et al.
JAMA 2004;291:300-300.
FULL TEXT
Novel Risk Factors for Atherosclerosis
von Eckardstein
JAMA 2004;291:301-301.
FULL TEXT
Traditional Risk Factors for Coronary Heart Disease
Root and Cobb
JAMA 2004;291:299-299.
FULL TEXT
Traditional Risk Factors for Coronary Heart Disease
Weissler
JAMA 2004;291:299-300.
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