Journal of Internal Medicine 2006; 260: doi: /j x

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1 Journal of Internal Medicine 2006; 260: doi: /j x Time trends in population cholesterol levels : influence of lipid-lowering drugs, obesity, smoking and educational level. The northern Sweden MONICA study M. ELIASSON 1,2, U. JANLERT 2, J.-H. JANSSON 2,3 & B. STEGMAYR 2 From the 1 Department of Medicine, Sunderby Hospital, Luleå; 2 Department of Public Health and Clinical Medicine, Umeå University, Umeå; and 3 Department of Medicine, Skellefteå Hospital, Skellefteå, Sweden Abstract. Eliasson M, Janlert U, Jansson J-H, Stegmayr B (Sunderby Hospital, Luleå; Umeå University, Umeå; and Skellefteå Hospital, Skellefteå, Sweden). Time trends in population cholesterol levels : influence of lipid-lowering drugs, obesity, smoking and educational level. The northern Sweden MONICA study. J Intern Med 2006; 260: Objectives. To explore time trends in population total cholesterol. Design and setting. Five population-based crosssectional surveys, in the northern Sweden MONICA study included 8827 men and women. Results. Age-adjusted cholesterol level declined in men, years old, from 6.38 to 5.78 mmol L )1 and in women from 6.32 to 5.51 mmol L )1. Between 1994 and 2004, subjects years old were included, and their levels also decreased, in men from 6.35 to 5.76 mmol L )1 and in women from 7.11 to 6.24 mmol L )1. The decrease was continuous over surveys and age groups, except in young and middle-aged men where no further decline was found after Cohorts born showed decreased cholesterol over the period, whilst no change was noted for those born thereafter. In 2004, one-fourth of men and onethird of women years achieved levels below 5.0 mmol L )1. Subjects with low educational level, body mass index 25 or smokers all had higher cholesterol levels which persisted during the 18-year period. In 2004, the 9% who used lipid-lowering drugs are estimated to contribute, at most, to 0.13 mmol L )1 lower cholesterol in the population. Conclusion. Large decreases in cholesterol levels occurred in the 18-year period. Less smoking may contribute to, and increasing obesity attenuate, this trend whilst lipid-lowering drugs have had little effect until recently. Socio-economic inequalities persist. Keywords: cholesterol, cohort, MONICA, obesity, smoking, socioeconomy. Introduction Cholesterol levels show a strong association with incidence and mortality from coronary heart disease in both men and women [1, 2]. In men, increased cholesterol also predicts stroke and all-cause mortality [2]. Recent European guidelines recommend that levels of total cholesterol in the population should be below 5 mmol L )1 [3]. In the MONICA project, mean total cholesterol levels in 38 populations in the mid-1980s ranged from 5.5 to 6.3 mmol L )1 [4]. Amongst those with the highest levels were the centres in Finland and northern Sweden. In the concluding reports from MONICA, a decline in total cholesterol level up to the mid-1990s was noted in two-thirds of the populations [5]. The average decrease over all populations during 10 years was only 0.08 mmol L )1 in men and 0.15 mmol L )1 in women. Longer time series, including recent data and with strict and uniform methodology, on population total cholesterol concentrations in Europe are scarce. Percentage fulfilment of the European recommendations is also unknown. Although total cholesterol levels mainly mirror the interaction between genetics and diet, the Ó 2006 Blackwell Publishing Ltd 551

2 552 M. ELIASSON et al. impact of other factors must be taken into account, most prominently the increasing use of lipid-lowering drugs [6 8]. Higher cholesterol levels were found with obesity [9, 10], smoking [11] and in groups with low socio-economic status [12 14] in Sweden reported up to 1999 [15]. As large changes in the use of lipid-lowering drugs, educational level, and the prevalence of regular smoking and obesity have occurred in most Western societies [5], an analysis of long-term trends in total cholesterol levels must take these factors into account. Our aim was to describe the trends in concentration of total cholesterol in the adult population of northern Sweden between 1986 and 2004, with emphasis on gender and age-specific patterns. Are trends influenced by the large changes in body mass index (BMI) and smoking? Are socio-economic inequities still present in the Swedish affluent society? What is the population impact of the increasing use of statins? Methods This study used data from the northern Sweden component of the WHO MONICA study. Briefly, information was collected during five populationbased surveys in 1986, 1990, 1994, 1999 and 2004 [16]. Subjects were randomly selected from population registers, stratified for age (25 64 years in the first two surveys, years in the latter) and gender, in the two most northern counties of Sweden (target population ). The five samples were independent of each other. Details of sampling and selection appear elsewhere [16]. A total of 8827 subjects, 4348 men and 4479 women with a valid total cholesterol value, participated in the five surveys (Table 1). Participation rates from 1986 and onwards were 82%, 77%, 75%, 71 and 74% in men and 80%, 80%, 78%, 74%, and 78% in women. Participants completed a questionnaire that focused on cardiovascular disease risk factors. All survey procedures were performed during the same season (January April) to minimize the seasonal variation in total cholesterol. Subjects were weighed on a daily calibrated balance scale in the first three surveys and on an electronic scale in the latter two. Blood samples were drawn after at least a 4-h fast and analysed without freezing. In 1986, 1990 and 1994, total cholesterol was determined by an enzymatic method (BM Monotest Cholesterol CHOD-PAP; Boehringer Mannheim GmbH, Mannheim, Germany), 1986 on a Multistat (Centrifugal analyser, ILS) and in 1990 and 1994 on a Hitachi 717 chemistry analyser (Roche, Basel, Switzerland). In 1999 and 2004, a dry chemistry method was used (Vitros 950; Kodak Echtachem, Rochester, NY, USA). The measurement of total cholesterol is accredited by the national accreditation body, SWEDAC, with a CV of 3.6% at 3.91 mmol L )1 and 3.1% at 6.66 mmol L )1. During the first three surveys the analytical quality of the total cholesterol measurements was checked continuously against standards from the WHO reference laboratory in Prague. In 1986, northern Sweden did not provide satisfactory results in the cholesterol analyses. We therefore reanalysed 104 frozen samples. The cholesterol levels were found to be too low and all values were adjusted Table 1 Cholesterol values according to age, gender and year of survey (mmol L )1 ) years years years years years , 175 ( ) 6.34, 212 ( ) 6.66, 225 (8 3) 6.77, 211 ( ) , 165 ( ) 6.14, 199 ( ) 6.54, 202 ( ) 6.76, 207 ( ) , 165 (8 5) 7, 179 (8 6.25) 6.29, 195 (6.14 4) 9, 208 ( ) 6.35, 192 ( ) , 155 ( ) 5.74, 159 ( ) 5, 170 ( ) 1, 196 ( ) 6.17, 206 (2 6.33) , 147 (4.90 2) 1, 166 ( ) 6.16, 181 ( ) 6.14, 213 ( ) 5.76, 220 (2 5.90) , 187 (5.39 9) 5.99, 206 ( ) 6.54, 212 ( ) 7.13, 197 ( ) , 175 ( ) 5.59, 205 ( ) 6.38, 207 ( ) 7.12, 212 ( ) , 172 ( ) 5.59, 201 ( ) 6, 209 ( ) 4, 202 ( ) 7.11, 191 ( ) , 163 ( ) 9, 175 ( ) 5.99, 202 ( ) 6.30, 196 ( ) 6.51, 192 ( ) , 165 ( ) 0, 195 ( ) 5.76, 197 (1 5.91) 6.20, 206 (3 6.37) 6.24, 212 (8 1) Values are presented as mean, n (95% CI).

3 TRENDS IN CHOLESTEROL LEVELS 553 using a univariate linear regression model. As the assay was changed between 1994 and 1999, we reanalysed 159 samples from the 1994 survey with the new method. In addition, a linear regression model was used to adjust the results from the 1999 and 2004 survey to the levels in 1994 to assure that comparisons would be accurate between the surveys. The highest attained educational level was classified as primary school (up to 9 years of school), secondary school (10 12 years of school) and university studies. Regular smokers smoked at least one cigarette a day; all other subjects were considered as nonsmokers. Cholesterol levels were categorized into three strata: <5.0 mmol L )1, mmol L )1 or 6.5 mmol L )1. BMI was categorized into healthy weight (<25), overweight ( ) and obesity ( 30). Subjects with BMI <18.5 (underweight) were excluded from the analysis of the effects of obesity (n ¼ 98). The 1994 survey and the surveys thereafter included the question Are you being treated with drugs to lower your cholesterol level? In order to validate the self-reported use of lipid-lowering drugs, we performed a substudy in the 2004 participants from Norrbotten County (approximately half of the participants) where a comprehensive database of case records and electronic prescriptions is operating with more than 95% of all prescriptions included. Of the 95 subject reporting use of these drugs, 89 were retrieved in the database and five of the remaining six had explicitly reported such drugs with brand names whilst answering the question Which drugs are you presently being treated with. We thus deemed the validity of self-reported use of lipidlowering agents as very high. Year of birth was stratified to create birth cohorts that included those age groups that were included in all surveys. Thus, the cohort born 1926 was the oldest to be represented at all five examinations. The first category included 4 years and the following ones included 10 years. Age- and gender-stratified means for total cholesterol are reported. A test for linear trends over the five surveys was performed by using anova for mean cholesterol levels and by using chi-square for categorical data. Age-adjusted values were calculated using a univariate linear general model. For comparisons of differences in mean cholesterol levels between categories of educational level, obesity and smoking, the whole 25- to 74-year sample was used whilst all analyses of time trends utilized only the 25- to 64-year group as data were not available for the oldest age group from the first two surveys. A stepwise, multiple linear regression was carried out with total cholesterol as dependent variable, and age, birth cohort, education level, obesity and smoking as independent variables. The software package SPSS (version 13.0) was used. The Research Ethics Committee of Umeå University and the National Computer Data Inspection Board approved the northern Sweden MONICA study. Participants gave written consent. Results Mean total cholesterol increased with age with the exception of the oldest men in 2004 who had lower values than those between age 45 and 64 years (Table 1, P < 0.001, anova test for linear trends). Cholesterol levels decreased continuously with each survey in all age groups (P < for all age groups, anova test for linear trend). However, the decline halted between the last two surveys in middle-aged and young men. Up to the age of 65 years, the mean decrease over the 18-year period was rather similar across age groups, mmol L )1 and mmol L )1 in men and women respectively. Amongst the oldest, years, similar decreases in cholesterol levels were achieved over 10 years observation. In men, years, age-adjusted mean cholesterol declined from 6.38 in 1986 to 5.78 mmol L )1 in 2004, and in women the decrease was from 6.32 to 5.51 mmol L )1 (Fig. 1, P < 0.001, anova test for 6 Fig. 1 Age-adjusted levels of total cholesterol in the population of northern Sweden, years old, (P < 0.001, test for linear trend).

4 554 M. ELIASSON et al. Table 2 Proportion of subjects between 25 and 64 years of age in different strata of cholesterol levels, with only primary school, obesity, regular smoking or using lipid-lowering drugs in five population surveys, (%) (P < for all trends but obesity in women where p was 0.002, test for linear trend) Cholesterol <5.0 mmol L ) >6.5 mmol L ) Only primary school Obesity (BMI 30) Smokers Users of lipid-lowering drugs* BMI, body mass index. *Proportion of subjects using lipid-lowering agents included subjects aged years. linear trend) corresponding to reductions of 9.3% and 13% in men and women respectively. Initially, levels were similar in men and women but in 1990 the female population had lower cholesterol. As no decrease was seen in men between 1999 and 2004, the gap between men and women in 2004 increased further to a total of 0.27 mmol L )1. The proportion of the population aged years with cholesterol levels above 6.5 mmol L )1 decreased by 14.2 percentage points and 22.9 percentage points between 1986 and 2004 in men and women respectively (Table 2). Simultaneously, the fraction with levels below 5.0 mmol L )1 increased by 12.6 percentage points and 24.5 percentage points in men and women respectively. A similar shift in the distribution was found for those aged years for the years (P ¼ in men and P < in women, test for linear trend). In 2004, one-fourth of the men aged years and one-third of women achieved levels below 5.0 mmol L )1 (Table 3). In all age groups but the Table 3 Proportion (%) of subjects with total cholesterol below 5 mmol L )1 according to age in 2004 (P < for linear trend across age groups, P for differences between men and women are given). For years, age-adjusted values by logistic regression are presented Age group (years) P-value <0.001 < <0.001 oldest, women, more often than men, reached these low levels. When examining population levels over the 18- year period according to birth cohort, it is evident that men and women born between 1926 and 1939 clearly showed decreased total cholesterol (P < 0.001, anova test for linear trends) in spite of ageing (Fig. 2). Moreover, in men born , levels decreased (P < 0.002) but in women a slight increase was noted (P ¼ 0.04). An increase was also found amongst men in the cohort (P ¼ 0.004) but for the remaining cohorts no significant time trends were noted. The proportion of subjects with only primary school as the highest level of education decreased sharply during the observation period (Table 2). Age-adjusted cholesterol levels were significantly lower amongst participants with university studies than amongst those with only secondary school, which in their turn had lower levels than those with only primary school education (Table 4). This gradient was more pronounced in women with a 0.52 mmol L )1 difference between university graduates and those with only primary education. In men, the decline in cholesterol levels started between 1990 and 1994 and was initially more rapid amongst those with a low educational level, thus narrowing the gap somewhat up to 1999 (Fig. 3). Between 1999 and 2004 an increase was noted amongst those with primary or secondary school whilst in university-educated the decrease continued. with only primary school or university studies had a similar and linear decrease, thus keeping the gap constant over the period. A faster decline was noted in women with secondary

5 TRENDS IN CHOLESTEROL LEVELS 555 Cholesterol levels according to year and cohort Mean cholesterol (mmol L 1 ) W o m e n M e n S e x Birth cohort Fig. 2 Total cholesterol levels in the population of northern Sweden according to birth cohort (for significance levels, see text) Year of survey 2004 Table 4 Age-adjusted mean cholesterol values according to level of education, body mass index, smoking and use of lipid-lowering drugs. Pooled data from five surveys ( ), age years. Data for lipid-lowering drugs only calculated from the 2004 survey Mean Lower CI Upper CI Mean Lower CI Upper CI Highest level of education Primary school Secondary school University Body mass index Normal Overweight Obese Smoking Nonsmokers Regular smokers Lipid-lowering drugs Yes No CI, 95% confidence interval. school, thus reaching levels similar to those observed in university-educated in Between 1986 and 2004, the prevalence of obesity increased markedly, more so in men than in women (Table 2). In men, BMI increased from 2 to 27.1 kg m )2 and in women from 25.0 to 26.3 kg m )2. Cholesterol levels in overweight or obese subjects were significantly higher than in those with normal weight (Table 4). There was no difference between obese and overweight participants. These findings were consistent over the 18-year period (Fig. 3). At the end of the observation period, only 11% of the men and 19% of the women were smokers, a decline which was much sharper in men than in women (Table 2). Both men and women who were regular smokers had significantly higher cholesterol levels than nonsmokers (Table 4). In the time trend analysis, restricted to age years, this difference diminished and vanished over time in men but remained unchanged in women (Fig. 3). A total of 286 subjects reported use of lipidlowering agents, increasing from 1.7% in 1994 to 10.4% in men and 7.6% in women in 2004.

6 556 M. ELIASSON et al. Primary Secondary University Primary Secondary University Normal Overweight Obese Normal Overweight Obese Non-smokers Smokers Non-smokers Smokers Fig. 3 Age-adjusted cholesterol levels according to highest attained level of education, presence of obesity or regular smoking for subjects years old (P < for all trends except men and women with university studies, P ¼ 0.001). Amongst participants aged years, 28% of the men and 22% of the women in 2004 used such drugs. Statins were the most common agents with only 2% treated with fibrates, 1% with cholestyramine and 1% with ezetimibe. Levels of total cholesterol were significantly lower amongst participants using any such drug than nonusers, calculated from only the 2004 survey (Table 4). Hypothesizing a decrease in cholesterol concentrations of 1.5 mmol L )1 with the use of statins in clinical praxis we recalculated what the population mean would have been in 2004, given no use at all of these drugs. Thus, a mean age-adjusted cholesterol of 5.86 mmol L )1 (95% CI ) was estimated when compared with the actually measured level of 5.73 mmol L )1 (7 5.78). Only amongst those aged years, the use of statins reduced population levels in a clinically significant manner from 6.37 mmol L )1 (6.27 7) to mmol L )1 ( ). A stepwise, multivariate linear regression in men points to survey year (calendar year) and age as the most important explanatory variables for total cholesterol levels, with minor impacts from obesity and smoking (data not shown). Birth cohort did not contribute to variations whilst higher education tended to explain lower cholesterol, although insignificantly. Altogether, these factors explained only 12% of the variability. In women, all factors except birth cohort contributed to explain variations in cholesterol levels but with somewhat higher impact than in men, thus explaining 27% of the variability. Discussion We report a continuous decline in total cholesterol levels of 10% in the population of northern Sweden from 1986 to The findings are uniform in all age and gender groups with the exception of men with only primary or secondary education where a levelling off was seen between 1999 and Clinically important differences were noted with higher cholesterol in subjects with only primary school, BMI at or above 25, or regular smoking. The

7 TRENDS IN CHOLESTEROL LEVELS 557 impact from lipid-lowering drugs on population cholesterol levels is so far very modest. Since the closing of the international MONICA project in the mid-1990s [5], only few reports on time trends in total cholesterol levels have been published. A recent US study reported a continuous decline from 1960 to 2002 of approximately 10% [6], but during the last 10 years, levels decreased from 5.31 to 7 mmol L )1 in the US [7]. In the North Karelia project, Finland, cholesterol levels decreased by 18% between 1972 and 1997 [17]. We have previously reported a decline in cholesterol between 1986 and 1999 in The northern Sweden MONICA study [15]. HDL cholesterol increased between 1986 and 1990 but decreased somewhat in In 2003, the European guidelines on cardiovascular disease prevention in clinical practice put forth a recommendation that total cholesterol should be below 5 mmol L )1 in the general population [3]. Little has yet been published regarding the fulfilment of this on a population level, but we now report a rapid increase in the proportion of the population with such low values, although women above 65 years of age still lag behind, perhaps due to less use of lipid-lowering drugs. Based on long-term follow-up data from large US cohorts, an increased level of total cholesterol of approximately 1 mmol L )1 would lead to an increased coronary mortality of 20 80%, with higher relative risk amongst the younger [1, 2]. A reduction in total cholesterol in the population by 10% was recently calculated to lead to a reduction in major cardiovascular events of 22% [18]. As incidence and mortality rates in myocardial infarction have decreased by 3 5% per year in the nondiabetic population of northern Sweden between 1989 and 2000, both in men and women [19], it is evident that a decrease in cholesterol levels of 0.7 mmol L )1 has strongly contributed to lower coronary heart disease morbidity. A close connection between socio-economic factors and cardiovascular morbidity has long been known [20]. This was recently confirmed in northern Sweden where both higher incidence and higher mortality in myocardial infarction and stroke were found amongst blue-collar workers than in subjects in nonmanual occupations [21]. The highest attained educational level is a good proxy for socio-economic status. High cholesterol concentrations in men and women with low socio-economic status have been noted since the early 1980s, both in the US [14] and more recently in Europe [12, 13]. In the US population, between 1985 and 1992, the trend in cholesterol reduction was similar across educational groups, thus maintaining the gap [14]. In the Danish MONICA study, no significant change was seen between 1982 and 1991 in any educational group [13]. We have previously shown strong and consistent inverse relationships between educational level and lipid concentrations between 1986 and 1999 in the northern Sweden MONICA study [15], but no more recent data on socio-economic differences in Europe have been published. We now extend and confirm this pattern and find no evidence of declining inequity. A direct and causal link between these two (low educational level and high cholesterol level) is improbable, and most probably low educational level is a marker for a set of life style habits which cause high cholesterol such as atherogenic diet, physical inactivity, obesity and smoking. Higher cholesterol levels in obese men and women were pointed out already in the early 1990s [9, 10], but in the US population this relationship seems to have weakened during the latest years [22]. Our data confirm higher levels not only in obese subjects, but also amongst those with only overweight, and point out that the higher levels persist in northern Sweden. It is possible that the slight increase in cholesterol in men in 2004 mirrors the fast increase in obesity in this group. If so, this underlines a possible future threat from obesity on the successful cardiovascular prevention in northern Sweden. An early meta-analysis found 3% higher levels of total cholesterol in smokers and pointed out that this may contribute significantly to the increased cardiovascular risk with smoking [11]. We found similar differences between smokers and nonsmokers, but in men this was no longer discernible in In contrast, women smokers still have higher total cholesterol levels. The cause of this relationship is presently not known but is probably related to dietary habits and socio-economic factors. Two per cent of the adult population was treated with lipid-lowering drugs in the UK in 1998 [8] and 12% in the USA in 1999 [7]. As we only included subjects up to the age of 75 years, the Swedish data from 2004 with 9% using such drugs, mainly

8 558 M. ELIASSON et al. statins, is comparable to the US conditions as of 5 years earlier. Assuming a decrease of at most 1.5 mmol L )1 with the use of 40 mg simvastatin in routine care [23], we hypothesize that this contributed only to 0.13 mmol L )1, or 2%, lower total cholesterol in the population in However, statins had a considerable impact in the oldest age group. As the most commonly prescribed dose of simvastatin in Sweden at that time was 20 mg, this calculation may be over-optimistic. These finding corroborate an analysis published in 2006 that, somewhat surprising, concluded that the declining blood pressure in the MONICA populations is not attributable to pharmacological treatment of subjects with high blood pressure but should be ascribed to other determinants [24]. The validity of our findings is strengthened by the strict and uniform use of the MONICA method over the whole period and maintaining a high participation rate. The main limitation is the lack of data on HDL cholesterol and triglycerides for the second part of the period. As most studies show a parallel decline in total cholesterol and LDL cholesterol [6], this would not threaten the public health relevance of our study. A thorough analysis of nonresponders showed that in the first four surveys nonresponders more often were smokers and had a somewhat lower BMI but there was no difference in educational level [25, 26]. Furthermore, the proportion reporting only high school in the 2004 survey was the same as in official Swedish statistics ( which strongly supports that our results are representative of our population. Thus, the effects of obesity, smoking and lipidlowering drugs on the populations mean cholesterol in northern Sweden are modest, at most. Although some effects of birth cohort were noted, these were no longer evident after taking age and other factors into account. Therefore, the slow decreasing trend is probably mainly due to dietary changes. This is supported by self-reported food intakes showing large changes from 1986 to 1999 with reduced consumption of foods with a high content of saturated fats [27]. A continuous decline in cholesterol concentrations heralds further reductions in cardiovascular disease, but strong socio-economic gradients persist, pointing out groups where intensified measures must be taken to change dietary habits, decrease obesity and decrease smoking. Conflict of interest statement None declared for any of the authors. Acknowledgements This study was supported by grants from the Swedish Research Council, the Research Council for Social Sciences, the Heart and Chest Fund, King Gustaf V s and Queen Victoria s Foundation, Västerbotten and Norrbotten County Councils, and the Swedish Public Health Institute. Dr Stegmayr is supported by a grant from the Swedish Medical Research Council. References 1 Lowe LP, Greenland P, Ruth KJ et al. Impact of major cardiovascular disease risk factors, particularly in combination, on 22-year mortality in women and men. Arch Intern Med 1998; 158: Stamler J, Daviglus ML, Garside DB et al. 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 2000; 284: De Backer G, Ambrosioni E, Borch-Johnsen K et al. European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J 2003; 24: Tuomilehto J, Kuulasmaa K, Torppa J. WHO MONICA project: geographic variation in mortality from cardiovascular diseases. Baseline data on selected population characteristics and cardiovascular mortality. World Health Stat Q 1987; 40: Kuulasmaa K, Tunstall-Pedoe H, Dobson A et al. Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA project populations. Lancet 2000; 355: Carroll MD, Lacher DA, Sorlie PD et al. Trends in serum lipids and lipoproteins of adults, JAMA 2005; 294: Ford ES, Mokdad AH, Giles WH et al. Serum total cholesterol concentrations and awareness, treatment, and control of hypercholesterolemia among US adults: findings from the National Health and Nutrition Examination Survey, 1999 to Circulation 2003; 107: Primatesta P, Poulter NR. Lipid concentrations and the use of lipid lowering drugs: evidence from a national cross-sectional survey. BMJ 2000; 321: Denke MA, Sempos CT, Grundy SM. Excess body weight. An under-recognized contributor to dyslipidemia in white American women. Arch Intern Med 1994; 154: Denke MA, Sempos CT, Grundy SM. Excess body weight. An underrecognized contributor to high blood cholesterol levels in white American men. Arch Intern Med 1993; 153:

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