Background The increased risk of cardiovascular disease associatedwith higher serum cholesterol levels in middle-aged personshas been clearly established, but there have been few opportunitiesto examine a potential link between serum cholesterol levelsmeasured in young men and clinically evident premature cardiovasculardisease later in life.
Methods We performed a prospective study of 1017 young men (meanage, 22 years) followed for 27 to 42 years to quantify the riskof cardiovascular disease and total mortality associated withserum cholesterol levels during early adult life. The mean serumcholesterol level at entry was 192 mg per deciliter (5.0 mmolper liter).
Results During a median follow-up of 30.5 years, there were125 cardiovascular-disease events, 97 of which were due to coronaryheart disease. The serum cholesterol level at base line wasstrongly associated with the incidence of events related tocoronary heart disease and cardiovascular disease, as well asto total mortality and mortality due to cardiovascular disease.The risks were similar whether the events occurred before orafter the age of 50. In a proportional-hazards analysis adjustedfor age, body-mass index (the weight in kilograms divided bythe square of the height in meters), the level of physical activity,coffee intake, change in smoking status, and the incidence ofdiabetes and hypertension during follow-up, a difference inthe serum cholesterol level at base line of 36 mg per deciliter(0.9 mmol per liter) -- the difference between the 25th and75th percentiles of cholesterol level in the study populationat base line -- was associated with an increased risk of cardiovasculardisease (relative risk, 1.72; 95 percent confidence interval,1.39 to 2.14), coronary heart disease (relative risk, 2.01;95 percent confidence interval, 1.59 to 2.53), and mortalitydue to cardiovascular disease (relative risk, 2.02; 95 percentconfidence interval, 1.23 to 3.32). A difference in the base-lineserum cholesterol level of 36 mg per deciliter was significantlyassociated with an increased risk of death before the age of50 (relative risk, 1.64; 95 percent confidence interval, 1.03to 2.61), but not with the overall risk of death (relative risk,1.21; 95 percent confidence interval, 0.93 to 1.58).
Conclusions These findings indicate a strong association betweenthe serum cholesterol level measured early in adult life inmen and cardiovascular disease in midlife.
Cardiovascular disease is the leading cause of death in middle-agedAmerican men1. In 1988, more than 41,000 U.S. residents diedof cardiovascular disease before the age of 50. Atherosclerosis,however, begins at a much earlier age. Fatty streaks are commonin the arterial walls of children, and a high prevalence ofcoronary-artery lesions has been found in young men who dieaccidentally or violently2,3,4,5. Children and adolescents withelevated serum cholesterol levels are more likely than theircounterparts with normal cholesterol levels to have parentswith coronary heart disease6. Higher serum cholesterol levelsin childhood have been associated with aortic atherosclerosisat autopsy in adolescents and young adults,7 and both aorticand coronary atherosclerosis in men ranging from 15 to 34 yearsof age have been correlated with postmortem cholesterol levels5.However, the risk of clinically evident coronary artery diseaseassociated with serum cholesterol levels measured during childhoodand early in adult life has not been determined. Most prospectivestudies of risk factors for clinical cardiovascular diseasehave examined middle-aged persons. Only a small minority ofthe participants in such studies were under 40 years of ageat entry8,9,10.
To characterize the risk of cardiovascular disease associatedwith the level of serum cholesterol in young men, we analyzeddata from a prospective study of white men. The unique featuresof this study include the measurement of cholesterol at a medianage of 22 years and follow-up for up to 42 years.
Methods
Study Population and Measurements
The Johns Hopkins Precursors Study was started in 194711. Atotal of 1337 students at Johns Hopkins Medical School who weremembers of the graduating classes of 1948 through 1964 wereenrolled; 1271 (95 percent) received a standardized medicalexamination and completed a questionnaire during medical school.Physical activity in medical school was defined as any "physicaltraining" occurring within the previous month, a measure shownto be protective against cardiovascular disease in this cohort12.Information about smoking habits, coffee intake, body weight,and drug treatment for hyperlipidemia was gathered at base lineand over the course of follow-up by means of annual questionnaires.It was not customary to obtain informed consent during the periodin which the base-line data were collected. After the establishmentof the Joint Committee on Clinical Investigation at our institution,the protocol for follow-up was reviewed and approved.
Starting with the class of 1949, serum cholesterol was measuredin the non-fasting state on multiple occasions during medicalschool with use of the Bloor method13. (Therefore, the 79 membersof the class of 1948 were not included in the analysis.) Thecoefficient of variation for the assay used in this study was5 percent. The number of measurements per subject ranged from1 to 11 (median, 3). For this analysis, the average of all cholesterolmeasurements obtained during medical school was used, and valueswere adjusted to correspond to the Abell-Kendall method14,15.In previous work from the Precursors Study, serum cholesterolvalues measured on a single occasion were used16,17,18. Theuse of the average of multiple determinations over time yieldsa more precise estimate of a person's true cholesterol value19.
A total of 1017 white men (90 percent of the white men in thestudy) had their serum cholesterol levels determined while inmedical school. These men form the basis of the present analysis.
Follow-up Procedures
The development of cardiovascular disease after graduation wasassessed by means of annual questionnaires. The present analysiswas based on events reported through December 31, 1991, representing27 to 42 years of follow-up. The yearly response rates rangedfrom 68 to 78 percent. Between 87 and 94 percent of the cohortresponded at least once over any five-year period. The vitalstatus of nonrespondents was ascertained by contacting familymembers, scanning obituaries, and searching the National DeathIndex through 1989. The vital status of more than 99 percentof the cohort was known. An end-points committee of five internistswho were also trained in epidemiology confirmed all reportsof morbidity and mortality due to cardiovascular disease. Aftera review of associated medical records, autopsy reports, anddeath certificates, a diagnosis was assigned with use of a modificationof the Lipid Research Clinics criteria classified accordingto the International Classification of Diseases, 9th Revision,Clinical Modification (ICD)20,21. Self-reports of the occurrenceof disease were very accurate. For example, medical recordswere obtained for 90 percent of the patients with myocardialinfarction, and the self-reported diagnosis was verified inevery instance.
Cardiovascular disease was categorized as follows. The mostspecific category, myocardial infarction, included myocardialinfarction (ICD 410 and 412) and sudden death (ICD 427.5 and798.2). Coronary heart disease included all events in the myocardial-infarctioncodes as well as angina pectoris (ICD 413), chronic ischemicheart disease (ICD 411), and other types of symptomatic coronarydisease that did not meet these criteria but required coronary-arterybypass surgery or percutaneous transluminal coronary angioplasty(ICD 414). The broadest category, cardiovascular disease, includedevents due to coronary heart disease as well as hypertensiveheart and renal diseases (ICD 402 to 404), congestive heartfailure (ICD 428), and cerebrovascular disease (ICD 430 to 438).
Statistical Analysis
After the frequency distribution of all variables was examined,the association of the serum cholesterol level, categorizedby quartiles, with possible confounders was assessed by chi-squareanalysis and analysis of variance. The relation of the serumcholesterol level at base line with the subsequent incidenceof disease was examined with Kaplan-Meier analysis22. The log-ranktest was used to assess whether the incidence of disease variedsignificantly according to the quartile of cholesterol level23.Follow-up began with the subjects' graduation from medical school.The interval between the beginning of follow-up and the occurrenceof an event was used as the time variable in all analyses ofsurvival. For categories in which a subject may have had morethan one type of event, only the first event to occur was usedin the analysis. To investigate whether the relation betweenthe serum cholesterol level measured in young adulthood andthe end points differed for events that occurred earlier asopposed to later in life, the analysis was repeated after theend points were stratified as occurring before the age of 50or as occurring at the age of 50 or later. To determine whetherthe associations of the serum cholesterol level with cardiovasculardisease were independent of other risk factors, Cox proportional-hazardsanalysis was used24. Multivariate analyses were performed inwhich serum cholesterol was used as both a continuous and acategorical (by quartile) variable. To account for possiblesecular trends in the serum cholesterol level and the incidenceof coronary heart disease, the Cox models were stratified accordingto calendar time: 1948 through 1957 and 1958 through 1964. Theintake of coffee, which has been associated with the incidenceof coronary heart disease in this cohort16,18; the level ofphysical activity; body-mass index (the weight in kilogramsdivided by the square of the height in meters); and the ageat graduation were also included in the multivariate models.In addition, the effects of a change in cigarette-smoking statusand the development of hypertension and diabetes during thecourse of follow-up were assessed by including time-dependentcovariates for these variables in the Cox models. The resultsof the proportional-hazards analysis are presented for a differencein the serum cholesterol level at base line of 36 mg per deciliter(0.9 mmol per liter), the difference between the 25th and the75th percentiles (interquartile range) of serum cholesterollevel in this study population at base line. This differencein serum cholesterol levels is clinically important, and a reductionof this magnitude in the cholesterol level could reasonablybe expected from a combined dietary and pharmacologic intervention.Hazard ratios are reported as relative risks with 95 percentconfidence intervals. All P values of 0.05 were consideredto indicate statistical significance (by a two-tailed test).
Results
The characteristics of the men in this analysis at base lineare presented in Table 1. In general, the participants wereyoung, healthy, and at low risk for cardiovascular disease.Their average age at entry into medical school was 22 years,and their average age at graduation was 26 years. The mean systolicand diastolic blood pressures and body-mass index were wellwithin the normal range. Only 36 (3.5 percent) of the men hadelevated blood pressures, as defined by a systolic pressureof 160 mm Hg or more, a diastolic pressure of 95 mm Hg or more,or both. Forty-eight (5 percent) of the men were overweight,as defined by a body-mass index of 27.8 or more. The averageserum cholesterol level was 192 mg per deciliter (5.0 mmol perliter). The difference in the mean cholesterol levels was greatestbetween the third and the fourth quartile: 32 mg per deciliter(0.8 mmol per liter). Almost half the men smoked during medicalschool, and 19 percent had engaged in physical training duringthe month before the base-line examination.
Table 1. Base-Line Characteristics of 1017 White Men, According to the Serum Cholesterol Level.
Men whose serum cholesterol levels were in the highest quartilewere slightly older at admission than their counterparts inthe other three quartiles (Table 1). Body-mass index, althoughwell within the normal range, was higher for each successivequartile of cholesterol. Coffee intake, blood pressure, degreeof physical activity, and prevalence of smoking were not associatedwith the serum cholesterol level.
Over the 27 to 42 years of follow-up, members of the cohortcontributed 27,871 person-years of observation, with a medianfollow-up of 30.5 years. At the end of follow-up in 1991, themean age of the cohort was 60 years (range, 50 to 89). A totalof 125 cardiovascular-disease events and 97 coronary-heart-diseaseevents were reported during follow-up (Table 2). Among the 95participants who died, death was attributed to cardiovasculardisease in 21, and 18 of these 21 subjects had coronary heartdisease (Table 2). The average age at the time of the diagnosisof coronary disease was 53 years. In 1985, only 10 men reportedbeing treated with drugs that lowered lipid levels; their meancholesterol level at base line was 225 mg per deciliter (5.8mmol per liter), which was significantly higher than that ofthe other members of the cohort (P<0.001). The cumulativeincidence of hypertension over the course of follow-up was 38.4percent; the cumulative incidence of diabetes mellitus was 6.0percent. The prevalence of smoking decreased from 48.1 percentat base line to 10.5 percent in 1986.
Table 2. Cumulative Incidence of Cardiovascular Disease and Total Mortality in 1017 White Men after 40 Years of Follow-up, According to the Base-Line Serum Cholesterol Level.
Univariate Analysis
The serum cholesterol level at base line was strongly associatedwith the subsequent incidence of coronary heart disease (Table 2and Figure 1), with a marked stepwise increase in the cumulativeincidence for successively higher quartiles of serum cholesterol.The same graded pattern of increasing risk with increasing levelsof serum cholesterol was seen for myocardial infarction, angina,and total cardiovascular disease. The risk associated with thebase-line serum cholesterol level was highest for myocardialinfarction and lowest for angina.
Figure 1. Cumulative Incidence of Cardiovascular Disease in 1017 White Men, According to the Serum Cholesterol Level at a Median Age of 22 Years.
To convert values for cholesterol to millimoles per liter, multiply by 0.02586. The numbers below the figure are the numbers of men included in the analysis at each time point.
There was also a graded relation between the base-line serumcholesterol level and total mortality (Table 2). Despite therelatively small number of deaths ascribed to cardiovasculardisease, participants with serum cholesterol levels in the highestquartile at base line had a markedly higher risk of death duringfollow-up than those with cholesterol levels in the lowest quartile(P<0.001).
The relative risks of disease associated with a difference inthe base-line serum cholesterol level of 36 mg per deciliter,derived by univariate Cox proportional-hazards analysis, areshown in Table 3. The risk associated with the serum cholesterollevel during young adulthood was essentially the same whetherthe cardiovascular events occurred before or after the age of50. For all the end points, including total mortality, therewas no evidence of a J-shaped relation with the serum cholesterollevel; the risk of disease was lowest in the men whose serumcholesterol levels were in the lowest eighth of the distribution.Moreover, the addition of quadratic terms (the square of thecholesterol level) did not improve the fit of the models.
Table 3. Relative Risk of Cardiovascular Disease Associated with a Difference in the Serum Cholesterol Level of 36 mg per Deciliter during Medical School in 1017 White Men as a Group and According to the Age of the Men at the Time of the Event.
Multivariate Analysis
The risk estimates associated with the serum cholesterol levelafter adjustment for covariates were remarkably similar to thosefrom the univariate analysis (Table 3). Higher serum cholesterollevels were associated with a greater risk of cardiovasculardisease and coronary heart disease that was independent of theother risk factors. As in the univariate analysis, the relativerisk was greatest for the development of myocardial infarctionand somewhat lower for angina pectoris. Each difference in thebase-line serum cholesterol level of 36 mg per deciliter wasassociated with a 72 percent increase in the risk of total cardiovasculardisease, a doubling of the risk of coronary heart disease andmyocardial infarction, and a 54 percent increase in the riskof angina. The risk of death from cardiovascular disease wasalso increased for higher base-line serum cholesterol levels.After an adjustment for the covariates listed above, the serumcholesterol level at base line was not associated with totalmortality, but was significantly associated with mortality fromall causes before the age of 50.
When the multivariate analysis was repeated with serum cholesterollevel as a categorical variable, similar results were obtained.The adjusted relative risk for the highest quartile as comparedwith the lowest quartile of serum cholesterol was 3.56 (95 percentconfidence interval, 1.78 to 7.11) for total cardiovasculardisease, 5.26 (95 percent confidence interval, 2.21 to 12.53)for coronary heart disease, 6.02 (95 percent confidence interval,2.10 to 17.22) for myocardial infarction, 2.25 (95 percent confidenceinterval, 0.80 to 6.32) for angina, 9.63 (95 percent confidenceinterval, 1.20 to 77.15) for mortality due to cardiovasculardisease, and 1.26 (95 percent confidence interval, 0.68 to 2.31)for mortality from all causes.
When the analyses were repeated with a single measurement ofserum cholesterol rather than the average of multiple measurements,the estimates of risk were somewhat lower. After adjustmentfor the covariates listed in Table 3, multivariate analysesshowed that the relative risk associated with a difference of36 mg per deciliter in the base-line serum cholesterol levelwas 1.50 (95 percent confidence interval, 1.22 to 1.84) forcardiovascular disease, 1.77 (95 percent confidence interval,1.41 to 2.21) for coronary heart disease, 2.01 (95 percent confidenceinterval, 1.23 to 3.27) for death from cardiovascular disease,and 1.22 (95 percent confidence interval, 0.95 to 1.56) fortotal mortality.
Discussion
This study demonstrated a strong, graded relation between theserum cholesterol level measured early in adult life in menand the subsequent incidence of coronary heart disease, cardiovasculardisease, and death from cardiovascular disease in midlife, whichwas independent of other risk factors. The average serum cholesterollevel of this group was well within the desirable level specifiedby current national guidelines and was lower than correspondingvalues in U.S. white men of similar age and with similar levelsof education in the period from 1960 through 196225,26. However,the risk of cardiovascular disease was increased even amongmen with serum cholesterol levels in the "normal" range. Inkeeping with previous studies in older adults, this relationwas stronger for coronary heart disease than for overall cardiovasculardisease27. Almost all the events in this analysis were prematurein the sense that over 95 percent occurred before the age of65. However, the risk associated with the base-line serum cholesterollevel did not differ markedly for events occurring before theage of 50 as compared with those that occurred later in life.Similar trends were noted for total mortality, without evidenceof an increased risk for those with the lowest levels of serumcholesterol at base line.
The measurement of serum cholesterol at a young age, the longduration of follow-up, and the availability of data on othercardiovascular risk factors at base line and during follow-upare the strengths of the present study. The high follow-up rateof the cohort and the accuracy of physicians' self-reports arealso major advantages. Few other studies have examined the riskof cardiovascular disease associated with characteristics assessedbefore midlife. Because the incidence of coronary artery diseasebefore the age of 40 is relatively low, studies of risk factorsin youth require very large samples or decades of follow-upin order to detect associations with cardiovascular disease.For example, although the present study was begun in 1947, onlywithin the past several years have enough events occurred toallow us to study risk factors for cardiovascular disease. Previousstudies of students entering college (average age, 18 years)and young aviators (average ages, 24 and 31) did not collectdata on serum cholesterol28,29,30.
Two possible biases could have contributed to the marked excessrisk of coronary heart disease in men with higher levels ofserum cholesterol at base line. Men with higher serum cholesterollevels may have been subjected to increased surveillance forcoronary disease. Thus, it is possible that mild, minimallysymptomatic coronary disease could have been more readily detectedin this group. In addition, the misdiagnosis of noncoronarysymptoms as coronary heart disease may have been more likelyin this group because of their elevated cholesterol levels.Similar associations with the base-line serum cholesterol levelwere observed for death from cardiovascular disease and totalmortality, however, making it very unlikely that such biasesaccounted for the associations. The lack of information on dietaryintake of fat and cholesterol is a limitation of the presentstudy. Although much of the risk associated with such intakewould probably be mediated through the serum cholesterol level,there may be additional mechanisms not accounted for in thepresent study31. No information was available on lipoproteinor apolipoprotein levels, because lipoprotein fractionationwas not yet being performed when this study was initiated. Onthe basis of studies of middle-aged men, lipoprotein fractionsor apolipoprotein levels would be expected to have an even strongerrelation with cardiovascular disease than with the total cholesterollevel27. Another potential limitation of this and most cohortstudies is that serum cholesterol levels were not assessed duringfollow-up. Considering the length of the follow-up and the limitationsin the measurement of the exposure variable, the strong relationof serum cholesterol measured at base line to future events,especially after the age of 50, is even more remarkable.
The homogeneous high socioeconomic status in this cohort permitsan estimation of the risk associated with the serum cholesterollevel at base line that is relatively unconfounded by socioeconomicstatus. These data are strictly applicable only to advantagedwhite men who have a lower absolute incidence of disease thanthe general population. But the similarity of the estimatesof the relative risk of cardiovascular disease in the presentstudy to those in community-based studies, in which serum cholesterolwas measured later in life, supports the idea that these findingscan be applied to men of other social classes9,32. If deathsdue to cardiovascular disease make up a greater proportion oftotal deaths in this group of white professionals than in thegeneral population, however, this study might overestimate therelative risk of total mortality associated with the base-lineserum cholesterol level, as compared with that in the generalpopulation.
In healthy young adults, the serum total cholesterol level isa strong predictor of clinically evident cardiovascular diseaseoccurring 25 or more years later. This relation was presenteven though this group had a favorable risk-factor profile forcardiovascular disease, and it persisted after an adjustmentfor changes in the risk factors during follow-up. It remainsfor future studies to demonstrate that interventions designedto lower the cholesterol level in young adulthood are effectivein the primary prevention of coronary heart disease and othertypes of cardiovascular disease.
Supported by grants (AG01760, HL42734, and RR00035) from theNational Institutes of Health. Dr. Klag is an Established Investigatorof the American Heart Association.
We are indebted to Dr. Caroline Bedell Thomas, who designedand initiated this study; to the members of the Johns HopkinsPrecursors Study, whose dedicated participation over the 42-yearperiod has made this work possible; and to Ms. Barbara Pawloskifor assistance in the preparation of the manuscript.
Source Information
From the Departments of Medicine (M.J.K., D.E.F., L.A.M., P.K.W., D.M.L.), Epidemiology (M.J.K., D.E.F., J.H., P.K.W.), Health Policy and Management (M.J.K., D.E.F., D.M.L.), and Biostatistics (K.-Y.L.), Johns Hopkins University School of Medicine and School of Hygiene and Public Health, Baltimore, and Peking Union Medical College and Chinese Academy of Medical Sciences, People's Republic of China (J.H.).
Address reprint requests to Dr. Klag at the Johns Hopkins Precursors Study, 550 N. Broadway, Rm. 503, Baltimore, MD 21205.
References
National Center for Health Statistics. Vital statistics of the United States, 1988. Vol. 2. Mortality. Part A. Washington, D.C.: Goverment Printing Office, 1991. (DHHS publication no. (PHS) 91-1101.)
Holman RL, McGill HC Jr, Strong JP, Geer JC. The natural history of atherosclerosis: the early aortic lesions as seen in New Orleans in the middle of the 20th century. Am J Pathol 1958;34:209-235.
Enos WF, Holmes RH, Beyer J. Coronary disease among United States soldiers killed in action in Korea: preliminary report. JAMA 1953;152:1090-1093.
McNamara JJ, Molot MA, Stremple JF, Cutting RT. Coronary artery disease in combat casualties in Vietnam. JAMA 1971;216:1185-1187. [Free Full Text]
Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking: a preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. JAMA 1990;264:3018-3024. [Free Full Text]
Thomas CB. Observations on some possible precursors of essential hypertension and coronary artery disease. V. Hypercholesteremia in healthy young adults. Am J Med Sci 1956;232:389-396. [Medline]
Newman WP, Freedman DS, Voors AW, et al. Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis: the Bogalusa Heart Study. N Engl J Med 1986;314:138-144. [Abstract]
The Pooling Project Research Group. Relationship of blood pressure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to incidence of major coronary events: final report of the Pooling Project. J Chronic Dis 1978;31:201-306. [CrossRef][Medline]
Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease: overall findings and differences by age for 316,099 white men. Arch Intern Med 1992;152:56-64. [Free Full Text]
Davey Smith G, Shipley MJ, Marmot MG, Rose G. Plasma cholesterol concentration and mortality: the Whitehall Study. JAMA 1992;267:70-76. [Free Full Text]
Thomas CB. Observations on some possible precursors of essential hypertension and coronary artery disease. Bull Johns Hopkins Hosp 1951;89:419-41.
Deckers JW, Klag MJ, Seidler AJ, Mead LA. Association of youthful and mid-life physical activity with subsequent development of cardiovascular disease (CVD). Circulation 1990;82:Suppl:III-259.abstract
Thomas CB, Eisenberg FF. Observations on the variability of total serum cholesterol in Johns Hopkins medical students. J Chronic Dis 1957;6:1-32.
Thomas CB, Murphy EA. Conversion of serum cholesterol levels from the Bloor to the Zak scales. Bull Johns Hopkins Hosp 1965;116:348-55.
Collins RA. A comparison of the Abell and modified ferric chloride total cholesterol methods. Am J Clin Pathol 1970;54:219-225. [Medline]
LaCroix AZ, Mead LA, Liang K-Y, Thomas CB, Pearson TA. Coffee consumption and the incidence of coronary heart disease. N Engl J Med 1986;315:977-982. [Abstract]
Coresh J, Klag MJ, Mead LA, Liang K-Y, Whelton PK. Vascular reactivity in young adults and cardiovascular disease: a prospective study. Hypertension 1992;19:Suppl II:II-218.
Klag MJ, Mead LA, LaCroix AZ, Liang K-Y, Pearson TA, Levine DM. Coffee intake and coronary heart disease. Circulation 1991;83:14-14.abstract
Liu K, Stamler J, Dyer A, McKeever J, McKeever P. Statistical methods to assess and minimize the role of intra-individual variability in obscuring the relationship between dietary lipids and serum cholesterol. J Chronic Dis 1978;31:399-418. [CrossRef][Medline]
Lipid Research Clinics Program. The Lipid Research Clinics coronary primary prevention trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984;251:351-364. [Free Full Text]
Department of Health and Human Services. The international classification of diseases, 9th rev., clinical modification: ICD-9-CM. Vol. 1. Diseases: tabular list. Washington, D.C.: Government Printing Office, 1980. (DHHS publication no. (PHS) 80-1260.)
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
Peto R, Peto J. Asymptomatically efficient rank invariant test procedures. J R Stat Soc [A] 1972;135:185-206.
Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-202.
The Expert Panel. Report of the National Cholesterol Education Program Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults. Arch Intern Med 1988;148:36-69. [Free Full Text]
National Center for Health Statistics -- National Heart, Lung, and Blood Institute Collaborative Lipid Group. Trends in serum cholesterol levels among US adults aged 20 to 74 years: data from the National Health and Nutrition Examination Surveys, 1960 to 1980. JAMA 1987;257:937-942. [Free Full Text]
Kannel WB, Gordon T, Castelli WP. Role of lipids and lipoprotein fractions in atherogenesis: the Framingham study. Prog Lipid Res 1981;20:339-348. [CrossRef][Medline]
Paffenbarger RS Jr, Notkin J, Krueger DE, et al. Chronic disease in former college students. II. Methods of study and observations on mortality from coronary heart disease. Am J Public Health 1966;56:962-971.
Rabkin SW, Mathewson FA, Hsu PH. Relation of body weight to development of ischemic heart disease in a cohort of young North American men after a 26 year observation period: the Manitoba Study. Am J Cardiol 1977;39:452-458. [CrossRef][Medline]
Oberman A, Lane NE, Harlan WR, Graybiel A, Mitchell RE. Trends in systolic blood pressure in the thousand aviator cohort over a twenty-four-year period. Circulation 1967;36:812-822. [Free Full Text]
Shekelle RB, Stamler J. Dietary cholesterol and ischaemic heart disease. Lancet 1989;1:1177-1178. [CrossRef][Medline]
Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984;251:365-374. [Free Full Text]
Reis, J. P., von Muhlen, D., Miller, E. R. III, Michos, E. D., Appel, L. J.
(2009). Vitamin D Status and Cardiometabolic Risk Factors in the United States Adolescent Population. Pediatrics
124: e371-e379
[Abstract][Full Text]
Marma, A. K., Lloyd-Jones, D. M.
(2009). Systematic Examination of the Updated Framingham Heart Study General Cardiovascular Risk Profile. Circulation
120: 384-390
[Abstract][Full Text]
Berry, J. D., Liu, K., Folsom, A. R., Lewis, C. E., Carr, J. J., Polak, J. F., Shea, S., Sidney, S., O'Leary, D. H., Chan, C., Lloyd-Jones, D. M.
(2009). Prevalence and Progression of Subclinical Atherosclerosis in Younger Adults With Low Short-Term but High Lifetime Estimated Risk For Cardiovascular Disease: The Coronary Artery Risk Development in Young Adults Study and Multi-Ethnic Study of Atherosclerosis. Circulation
119: 382-389
[Abstract][Full Text]
Kwiterovich, P. O. Jr.
(2008). Recognition and Management of Dyslipidemia in Children and Adolescents. J. Clin. Endocrinol. Metab.
93: 4200-4209
[Abstract][Full Text]
Leunissen, R. W. J., Kerkhof, G. F., Stijnen, T., Hokken-Koelega, A. C. S.
(2008). Fat Mass and Apolipoprotein E Genotype Influence Serum Lipoprotein Levels in Early Adulthood, whereas Birth Size Does Not. J. Clin. Endocrinol. Metab.
93: 4307-4314
[Abstract][Full Text]
Wittink, M. N., Morales, K. H., Meoni, L. A., Ford, D. E., Wang, N.-y., Klag, M. J., Gallo, J. J.
(2008). Stability of Preferences for End-of-Life Treatment After 3 Years of Follow-up: The Johns Hopkins Precursors Study. Arch Intern Med
168: 2125-2130
[Abstract][Full Text]
Mielke, M. M., Xue, Q.-L., Zhou, J., Chaves, P. H. M., Fried, L. P., Carlson, M. C.
(2008). Baseline Serum Cholesterol Is Selectively Associated With Motor Speed and Not Rates of Cognitive Decline: The Women's Health and Aging Study II. Journals of Gerontology Series A: Biological Sciences and Medical Sciences
63: 619-624
[Abstract][Full Text]
Criqui, M. H.
(2007). Triglycerides and Coronary Heart Disease Revisited (Again). ANN INTERN MED
147: 425-427
[Full Text]
Loria, C. M., Liu, K., Lewis, C. E., Hulley, S. B., Sidney, S., Schreiner, P. J., Williams, O. D., Bild, D. E., Detrano, R.
(2007). Early Adult Risk Factor Levels and Subsequent Coronary Artery Calcification: The CARDIA Study. J Am Coll Cardiol
49: 2013-2020
[Abstract][Full Text]
Kittleson, M. M., Meoni, L. A., Wang, N.-Y., Chu, A. Y., Ford, D. E., Klag, M. J.
(2006). Association of Childhood Socioeconomic Status With Subsequent Coronary Heart Disease in Physicians. Arch Intern Med
166: 2356-2361
[Abstract][Full Text]
Ruan, X. Z., Moorhead, J. F., Tao, J. L., Ma, K. L., Wheeler, D. C., Powis, S. H., Varghese, Z.
(2006). Mechanisms of Dysregulation of Low-Density Lipoprotein Receptor Expression in Vascular Smooth Muscle Cells by Inflammatory Cytokines. Arterioscler. Thromb. Vasc. Bio.
26: 1150-1155
[Abstract][Full Text]
Lloyd-Jones, D. M., Leip, E. P., Larson, M. G., D'Agostino, R. B., Beiser, A., Wilson, P. W.F., Wolf, P. A., Levy, D.
(2006). Prediction of Lifetime Risk for Cardiovascular Disease by Risk Factor Burden at 50 Years of Age. Circulation
113: 791-798
[Abstract][Full Text]
McVeigh, B. L, Dillingham, B. L, Lampe, J. W, Duncan, A. M
(2006). Effect of soy protein varying in isoflavone content on serum lipids in healthy young men. Am. J. Clin. Nutr.
83: 244-251
[Abstract][Full Text]
Jaschke, B., Michaelis, C., Milz, S., Vogeser, M., Mund, T., Hengst, L., Kastrati, A., Schomig, A., Wessely, R.
(2005). Local statin therapy differentially interferes with smooth muscle and endothelial cell proliferation and reduces neointima on a drug-eluting stent platform. Cardiovasc Res
68: 483-492
[Abstract][Full Text]
Zhang, B., Kaneshi, T., Ohta, T., Saku, K.
(2005). Relation between insulin resistance and fast-migrating LDL subfraction as characterized by capillary isotachophoresis. J. Lipid Res.
46: 2265-2277
[Abstract][Full Text]
Jarfelt, M, Lannering, B, Bosaeus, I, Johannsson, G, Bjarnason, R
(2005). Body composition in young adult survivors of childhood acute lymphoblastic leukaemia. Eur J Endocrinol
153: 81-89
[Abstract][Full Text]
Makedou, A., Kourti, M., Makedou, K., Lazaridou, S., Varlamis, G.
(2005). Lipid Profile of Children with a Family History of Coronary Heart Disease or Hyperlipidemia: 9-Year Experience of an Outpatient Clinic for the Prevention of Cardiovascular Diseases. ANGIOLOGY
56: 391-395
[Abstract]
Kopple, J. D
(2005). The phenomenon of altered risk factor patterns or reverse epidemiology in persons with advanced chronic kidney failure. Am. J. Clin. Nutr.
81: 1257-1266
[Abstract][Full Text]
Mielke, M. M., Zandi, P. P., Sjogren, M., Gustafson, D., Ostling, S., Steen, B., Skoog, I.
(2005). High total cholesterol levels in late life associated with a reduced risk of dementia. Neurology
64: 1689-1695
[Abstract][Full Text]
McCarron, P., Davey Smith, G.
(2005). Commentary: Incubation of coronary heart disease--recent developments. Int J Epidemiol
34: 248-250
[Full Text]
Kalantar-Zadeh, K., Abbott, K. C, Salahudeen, A. K, Kilpatrick, R. D, Horwich, T. B
(2005). Survival advantages of obesity in dialysis patients. Am. J. Clin. Nutr.
81: 543-554
[Abstract][Full Text]
Woodard, L. D., Kressin, N. R., Petersen, L. A.
(2004). Is Lipid-Lowering Therapy Underused by African Americans at High Risk of Coronary Heart Disease Within the VA Health Care System?. AJPH
94: 2112-2117
[Abstract][Full Text]
Sposito, A. C., Gonbert, S., Turpin, G., Chapman, M. J., Thillet, J.
(2004). Common Promoter C516T Polymorphism in the ApoB Gene Is an Independent Predictor of Carotid Atherosclerotic Disease in Subjects Presenting a Broad Range of Plasma Cholesterol Levels. Arterioscler. Thromb. Vasc. Bio.
24: 2192-2195
[Abstract][Full Text]
Criqui, M. H., Golomb, B. A.
(2004). Low and lowered cholesterol and total mortality. J Am Coll Cardiol
44: 1009-1010
[Full Text]
Galobardes, B., Lynch, J. W., Davey Smith, G.
(2004). Childhood Socioeconomic Circumstances and Cause-specific Mortality in Adulthood: Systematic Review and Interpretation. Epidemiol Rev
26: 7-21
[Full Text]
Kalantar-Zadeh, K., Block, G., Horwich, T., Fonarow, G. C.
(2004). Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure. J Am Coll Cardiol
43: 1439-1444
[Abstract][Full Text]
Li, S., Chen, W., Srinivasan, S. R., Bond, M. G., Tang, R., Urbina, E. M., Berenson, G. S.
(2003). Childhood Cardiovascular Risk Factors and Carotid Vascular Changes in Adulthood: The Bogalusa Heart Study. JAMA
290: 2271-2276
[Abstract][Full Text]
Raitakari, O. T., Juonala, M., Kahonen, M., Taittonen, L., Laitinen, T., Maki-Torkko, N., Jarvisalo, M. J., Uhari, M., Jokinen, E., Ronnemaa, T., Akerblom, H. K., Viikari, J. S. A.
(2003). Cardiovascular Risk Factors in Childhood and Carotid Artery Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study. JAMA
290: 2277-2283
[Abstract][Full Text]
Lloyd-Jones, D. M., Wilson, P. W. F., Larson, M. G., Leip, E., Beiser, A., D'Agostino, R. B., Cleeman, J. I., Levy, D.
(2003). Lifetime Risk of Coronary Heart Disease by Cholesterol Levels at Selected Ages. Arch Intern Med
163: 1966-1972
[Abstract][Full Text]
Kwiterovich, P. O. Jr, Vining, E. P. G., Pyzik, P., Skolasky, R. Jr, Freeman, J. M.
(2003). Effect of a High-Fat Ketogenic Diet on Plasma Levels of Lipids, Lipoproteins, and Apolipoproteins in Children. JAMA
290: 912-920
[Abstract][Full Text]
Letexier, D., Diraison, F., Beylot, M.
(2003). Addition of inulin to a moderately high-carbohydrate diet reduces hepatic lipogenesis and plasma triacylglycerol concentrations in humans. Am. J. Clin. Nutr.
77: 559-564
[Abstract][Full Text]
Klein, L. W., Nathan, S.
(2003). Coronary artery disease in young adults. J Am Coll Cardiol
41: 529-531
[Full Text]
Greenland, P., Gidding, S. S, Tracy, R. P
(2002). Commentary: Lifelong prevention of atherosclerosis: the critical importance of major risk factor exposures. Int J Epidemiol
31: 1129-1134
[Full Text]
Stone, N.
(2002). Combination therapy: its rationale and the role of ezetimibe. Eur Heart J Suppl
4: J19-J22
[Abstract]
Colao, A., Di Somma, C., Salerno, M., Spinelli, L., Orio, F., Lombardi, G.
(2002). The Cardiovascular Risk of GH-Deficient Adolescents. J. Clin. Endocrinol. Metab.
87: 3650-3655
[Abstract][Full Text]
Matvienko, O. A, Lewis, D. S, Swanson, M., Arndt, B., Rainwater, D. L, Stewart, J., Alekel, D L.
(2002). A single daily dose of soybean phytosterols in ground beef decreases serum total cholesterol and LDL cholesterol in young, mildly hypercholesterolemic men. Am. J. Clin. Nutr.
76: 57-64
[Abstract][Full Text]
Querfeld, U.
(2002). Is atherosclerosis accelerated in young patients with end-stage renal disease? The contribution of paediatric nephrology. Nephrol Dial Transplant
17: 719-722
[Full Text]
Chang, P. P., Ford, D. E., Meoni, L. A., Wang, N.-Y., Klag, M. J.
(2002). Anger in Young Men and Subsequent Premature Cardiovascular Disease: The Precursors Study. Arch Intern Med
162: 901-906
[Abstract][Full Text]
McCarron, P., Okasha, M., McEwen, J., Smith, G. D.
(2002). McCarron et al. Respond to "Height-Cardiovascular Disease Relation": Are All Risk Factors Equal?. Am J Epidemiol
155: 690-691
[Full Text]
Klag, M. J., Wang, N.-Y., Meoni, L. A., Brancati, F. L., Cooper, L. A., Liang, K.-Y., Young, J. H., Ford, D. E.
(2002). Coffee Intake and Risk of Hypertension: The Johns Hopkins Precursors Study. Arch Intern Med
162: 657-662
[Abstract][Full Text]
Takemoto, M., Liao, J. K.
(2001). Pleiotropic Effects of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors. Arterioscler. Thromb. Vasc. Bio.
21: 1712-1719
[Abstract][Full Text]
LaRosa, J. C.
(2001). Prevention and Treatment of Coronary Heart Disease: Who Benefits?. Circulation
104: 1688-1692
[Abstract][Full Text]
Miura, K., Daviglus, M. L., Dyer, A. R., Liu, K., Garside, D. B., Stamler, J., Greenland, P.
(2001). Relationship of Blood Pressure to 25-Year Mortality Due to Coronary Heart Disease, Cardiovascular Diseases, and All Causes in Young Adult Men: The Chicago Heart Association Detection Project in Industry. Arch Intern Med
161: 1501-1508
[Abstract][Full Text]
Cui, Y., Blumenthal, R. S., Flaws, J. A., Whiteman, M. K., Langenberg, P., Bachorik, P. S., Bush, T. L.
(2001). Non-High-Density Lipoprotein Cholesterol Level as a Predictor of Cardiovascular Disease Mortality. Arch Intern Med
161: 1413-1419
[Abstract][Full Text]
Vidon, C., Boucher, P., Cachefo, A., Peroni, O., Diraison, F., Beylot, M.
(2001). Effects of isoenergetic high-carbohydrate compared with high-fat diets on human cholesterol synthesis and expression of key regulatory genes of cholesterol metabolism. Am. J. Clin. Nutr.
73: 878-884
[Abstract][Full Text]
Navas-Nacher, E. L., Colangelo, L., Beam, C., Greenland, P.
(2001). Risk Factors for Coronary Heart Disease in Men 18 to 39 Years of Age. ANN INTERN MED
134: 433-439
[Abstract][Full Text]
Simell, O., Niinikoski, H., Ronnemaa, T., Lapinleimu, H., Routi, T., Lagstrom, H., Salo, P., Jokinen, E., Viikari, J.
(2000). Special Turku Coronary Risk Factor Intervention Project for Babies (STRIP). Am. J. Clin. Nutr.
72
: 1316S-1331S
[Abstract][Full Text]
Forrester, J. S., Bairey-Merz, C. N., Kaul, S.
(2000). The aggressive low density lipoprotein lowering controversy. J Am Coll Cardiol
36: 1419-1425
[Abstract][Full Text]
Gelber, A. C., Hochberg, M. C., Mead, L. A., Wang, N.-Y., Wigley, F. M., Klag, M. J.
(2000). Joint Injury in Young Adults and Risk for Subsequent Knee and Hip Osteoarthritis. ANN INTERN MED
133: 321-328
[Abstract][Full Text]
Rask-Nissila, L., Jokinen, E., Terho, P., Tammi, A., Lapinleimu, H., Ronnemaa, T., Viikari, J., Seppanen, R., Korhonen, T., Tuominen, J., Valimaki, I., Simell, O.
(2000). Neurological Development of 5-Year-Old Children Receiving a Low-Saturated Fat, Low-Cholesterol Diet Since Infancy: A Randomized Controlled Trial. JAMA
284: 993-1000
[Abstract][Full Text]
Stamler, J., Daviglus, M. L., Garside, D. B., Dyer, A. R., Greenland, P., Neaton, J. D.
(2000). Relationship of Baseline Serum Cholesterol Levels in 3 Large Cohorts of Younger Men to Long-term Coronary, Cardiovascular, and All-Cause Mortality and to Longevity. JAMA
284: 311-318
[Abstract][Full Text]
Grundy, S. M.
(2000). Early Detection of High Cholesterol Levels in Young Adults. JAMA
284: 365-367
[Full Text]
Tsiodras, S., Mantzoros, C., Hammer, S., Samore, M.
(2000). Effects of Protease Inhibitors on Hyperglycemia, Hyperlipidemia, and Lipodystrophy: A 5-Year Cohort Study. Arch Intern Med
160: 2050-2056
[Abstract][Full Text]
Matthan, N. R., Ausman, L. M., Lichtenstein, A. H., Jones, P. J. H.
(2000). Hydrogenated fat consumption affects cholesterol synthesis in moderately hypercholesterolemic women. J. Lipid Res.
41: 834-839
[Abstract][Full Text]
Leeson, C. P. M., Whincup, P. H., Cook, D. G., Mullen, M. J., Donald, A. E., Seymour, C. A., Deanfield, J. E.
(2000). Cholesterol and Arterial Distensibility in the First Decade of Life : A Population-Based Study. Circulation
101: 1533-1538
[Abstract][Full Text]
Grundy, S. M., Bazzarre, T., Cleeman, J., D’Agostino, R. B. Sr, Hill, M., Houston-Miller, N., Kannel, W. B., Krauss, R., Krumholz, H. M., Lauer, R. M., Ockene, I. S., Pasternak, R. C., Pearson, T., Ridker, P. M., Wood, D.
(2000). Prevention Conference V : Beyond Secondary Prevention : Identifying the High-Risk Patient for Primary Prevention : Medical Office Assessment : Writing Group I. Circulation
101
: e3-e11
[Full Text]
Radunovic, N., Kuczynski, E., Rosen, T., Dukanac, J., Petkovic, S., Lockwood, C. J.
(2000). Plasma Apolipoprotein A-I and B Concentrations in Growth-Retarded Fetuses: A Link between Low Birth Weight and Adult Atherosclerosis. J. Clin. Endocrinol. Metab.
85: 85-88
[Abstract][Full Text]
(1999). Discontinuation of Growth Hormone (GH) Treatment: Metabolic Effects in GH-Deficient and GH-Sufficient Adolescent Patients Compared with Control Subjects. J. Clin. Endocrinol. Metab.
84: 4516-4524
[Abstract][Full Text]
Grundy, S. M.
(1999). Primary Prevention of Coronary Heart Disease : Integrating Risk Assessment With Intervention. Circulation
100: 988-998
[Full Text]
Ford, D. E., Mead, L. A., Chang, P. P., Cooper-Patrick, L., Wang, N.-Y., Klag, M. J.
(1998). Depression Is a Risk Factor for Coronary Artery Disease in Men: The Precursors Study. Arch Intern Med
158: 1422-1426
[Abstract][Full Text]
Grundy, S. M., Balady, G. J., Criqui, M. H., Fletcher, G., Greenland, P., Hiratzka, L. F., Houston-Miller, N., Kris-Etherton, P., Krumholz, H. M., LaRosa, J., Ockene, I. S., Pearson, T. A., Reed, J., Washington, R., Smith, S. C. Jr
(1998). Primary Prevention of Coronary Heart Disease: Guidance From Framingham : A Statement for Healthcare Professionals From the AHA Task Force on Risk Reduction. Circulation
97: 1876-1887
[Full Text]
Kilby, M. D., Neary, R. H., Mackness, M. I., Durrington, P. N.
(1998). Fetal and Maternal Lipoprotein Metabolism in Human Pregnancy Complicated by Type I Diabetes Mellitus. J. Clin. Endocrinol. Metab.
83: 1736-1741
[Abstract][Full Text]
Borgia, M. C., Medici, F.
(1998). Perspectives in the Treatment of Dyslipidemias in the Prevention of Coronary Heart Disease. ANGIOLOGY
49: 339-348
[Abstract]
Cullen, P., Schulte, H., Assmann, G.
(1997). The Munster Heart Study (PROCAM) : Total Mortality in Middle-Aged Men Is Increased at Low Total and LDL Cholesterol Concentrations in Smokers but Not in Nonsmokers. Circulation
96: 2128-2136
[Abstract][Full Text]
Freedman, D. S., Serdula, M. K., Percy, C. A., Ballew, C., White, L.
(1997). Obesity, Levels of Lipids and Glucose, and Smoking among Navajo Adolescents. J. Nutr.
127: 2120-2120
[Abstract][Full Text]
Gelber, A. C., Klag, M. J., Mead, L. A., Thomas, J., Thomas, D. J., Pearson, T. A., Hochberg, M. C.
(1997). Gout and Risk for Subsequent Coronary Heart Disease: The Meharry-Hopkins Study. Arch Intern Med
157: 1436-1440
[Abstract]
Fitch, J., Garcia, R. E., Moodie, D. S., Secic, M.
(1997). Influence of Cholesterol Screening and Nutritional Counseling in Reducing Cholesterol Levels in Children. CLIN PEDIATR
36: 267-272
[Abstract]
Niinikoski, H., Lapinleimu, H., Viikari, J., Ronnemaa, T., Jokinen, E., Seppanen, R., Terho, P., Tuominen, J., Valimaki, I., Simell, O.
(1997). Growth Until 3 Years of Age in a Prospective, Randomized Trial of a Diet With Reduced Saturated Fat and Cholesterol. Pediatrics
99: 687-694
[Abstract][Full Text]
Cleeman, J. I., Grundy, S. M.
(1997). National Cholesterol Education Program Recommendations for Cholesterol Testing in Young Adults : A Science-Based Approach. Circulation
95: 1646-1650
[Full Text]
LaRosa, J. C., Pearson, T. A.
(1997). Cholesterol Screening Guidelines : Consensus, Evidence, and the Departure From Common Sense. Circulation
95: 1651-1653
[Full Text]
McGill, H. C. Jr, McMahan, C. A., Malcom, G. T., Oalmann, M. C., Strong, J. P.
(1997). Effects of Serum Lipoproteins and Smoking on Atherosclerosis in Young Men and Women. Arterioscler. Thromb. Vasc. Bio.
17: 95-106
[Abstract][Full Text]
Bao, W., Srinivasan, S. R., Wattigney, W. A., Bao, W., Berenson, G. S.
(1996). Usefulness of Childhood Low-Density Lipoprotein Cholesterol Level in Predicting Adult Dyslipidemia and Other Cardiovascular Risks: The Bogalusa Heart Study. Arch Intern Med
156: 1315-1320
[Abstract]
(1996). Cholesterol Screening in Asymptomatic Adults : No Cause to Change. Circulation
93: 1067-1068
[Full Text]
Iribarren, C., Reed, D. M., Chen, R., Yano, K., Dwyer, J. H.
(1995). Low Serum Cholesterol and Mortality : Which Is the Cause and Which Is the Effect?. Circulation
92: 2396-2403
[Abstract][Full Text]
Verschuren, W M M., Kromhout, D.
(1995). Total cholesterol concentration and mortality at a relatively young age: Do men and women differ?. BMJ
311: 779-783
[Abstract][Full Text]
Denke, M. A., Winker, M. A.
(1995). Cholesterol and Coronary Heart Disease in Older Adults: No Easy Answers. JAMA
274: 575-577
[Abstract]
Iribarren, C., Reed, D. M., Burchfiel, C. M., Dwyer, J. H.
(1995). Serum Total Cholesterol and Mortality: Confounding Factors and Risk Modification in Japanese-American Men. JAMA
273: 1926-1932
[Abstract]
Havel, R. J., Rapaport, E.
(1995). Management of Primary Hyperlipidemia. NEJM
332: 1491-1498
[Full Text]
Levine, G. N., Keaney, J. F., Vita, J. A.
(1995). Cholesterol Reduction in Cardiovascular Disease -- Clinical Benefits and Possible Mechanisms. NEJM
332: 512-521
[Full Text]
Law, M R, Thompson, S G, Wald, N J
(1994). Assessing possible hazards of reducing serum cholesterol. BMJ
308: 373-379
[Abstract][Full Text]
Lane, D. M.
(1993). Blood Cholesterol Measurement in Young Adults. JAMA
270: 936-936
[Abstract]
Corvilain, B., Matte, J., Litvine, C., Klag, M. J., Mead, L. A., Levine, D. M.
(1993). Serum Cholesterol in Young Men and Cardiovascular Disease. NEJM
329: 138-138
[Full Text]
Stamler, J.
(1993). Epidemic Obesity in the United States. Arch Intern Med
153: 1040-1044
[Abstract]
Hulley, S. B., Newman, T. B., Grady, D., Garber, A. M., Baron, R. B., Browner, W. S.
(1993). Should We Be Measuring Blood Cholesterol Levels in Young Adults?. JAMA
269: 1416-1419
[Abstract]
(1993). HIGH CHOLESTEROL IN YOUNG MEN PREDICTS CARDIOVASCULAR DISEASE. JWatch General
1993: 3-3
[Full Text]
0.05 were considered to indicate statistical significance (by a two-tailed test). 
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