Trends in Serum Lipids and Lipoproteins of Adults, 1960-2002 FREE

A number of epidemiological studies have investigated the association between lipids and atherosclerotic disease. The Framingham Heart Study¹ has assessed longitudinal trends in lipid levels and their association with atherosclerotic disease, with data collection beginning in 1948. Examples of other longitudinal studies in the United States are the Atherosclerosis Risk in Communities study,² the Cardiovascular Heart Study,³ the Coronary Artery Risk Development in Young Adults study,⁴ and the Multi-Ethnic Study of Atherosclerosis.⁵

The Multinational Monitoring of Trends and Determinants in Cardiovascular Disease study⁶ is an international study of adults aged 35 to 64 years in 21 countries on 4 continents. In this study, total cholesterol levels of adults aged 35 to 64 years showed a decline in mean serum total cholesterol from the mid-1980s to the mid-1990s in approximately half of the European populations included in the study.⁷

The National Health Examination Survey (NHES) and the National Health and Nutrition Examination Surveys (NHANES) conducted by the National Center for Health Statistics/Centers for Disease Control and Prevention (NCHS/CDC) are unique among US studies. In NHANES, a wide battery of health-related data, including serum lipids, were collected from a representative sample of the US civilian noninstitutionalized population in standardized examinations. Through these surveys, the NCHS/CDC has been obtaining population estimates of serum total cholesterol since 1960 and high-density lipoprotein (HDL) cholesterol and serum triglyceride since 1976.

Analysis of data from NHANES surveys has shown consistent declines in the mean serum total cholesterol levels of adults and in the percentage of adults with serum total cholesterol level of at least 240 mg/dL (≥6.22 mmol/L) between 1960 and 1994.^8- 9 Levels of HDL cholesterol and very low-density lipoprotein cholesterol did not change significantly in adults, suggesting that the decline in total cholesterol levels was due to a decline in low-density lipoprotein (LDL) cholesterol levels only. Recently, using data from NHANES 1999-2000, the study by Ford et al¹⁰ concluded that the rate of decline in mean serum total cholesterol concentrations of the adult US population observed from 1960-1962 to 1988-1994 had slowed between 1988-1994 and 1999-2000.

During the 1990s, public health messages emphasized low saturated fat and low cholesterol diets, maintenance of healthy weight, and increased physical activity.^11- 13 Furthermore, numerous clinical trials demonstrated the efficacy and safety of lipid-lowering drugs, primarily statins, in reducing coronary heart disease (CHD) risk.^14- 15

Our goal was to present data on total cholesterol, LDL cholesterol, HDL cholesterol, and serum triglyceride levels from NHANES 1999-2002, the most recent NHANES survey, to evaluate trends in lipids between 1960 and 2002, including the percentage with a serum total cholesterol level of at least 240 mg/dL (≥6.22 mmol/L), and to examine potential contributing factors to the trends observed.

NHANES and NHES constitute a series of cross-sectional, nationally representative, area probability surveys conducted by the NCHS/CDC. The procedures for selecting the sample and conducting the interviews and examinations for NHANES 1999-2002 were similar to the procedures for previous surveys.¹⁶ The NHANES design is a stratified, multistage, probability sample. Detailed descriptions of each survey have been published.^17- 20

Trends in mean serum total cholesterol for adults are based on comparisons of data on adults aged 20 to 74 years from 5 surveys: NHES I (1960-1962) (n = 6098), NHANES I (1971-1974) (n = 13 106), NHANES II (1976-1980) (n = 11 864), NHANES III (1988-1994) (n = 13 914), and NHANES 1999-2002 (n = 7740). Trends in triglyceride, HDL cholesterol, and LDL cholesterol levels (available for NHANES II, NHANES III, and NHANES 1999-2002) are based on comparisons of data from these 3 surveys.

Serum lipid levels were measured for adults aged 20 years or older in NHANES III (n=15 719) and NHANES 1999-2002 (n=8809), but only for adults 20 to 74 years in previous surveys. Race/ethnicity categories are based on self-reported data using the census categories from the Office of Management and Budget directives.²¹ Estimates of mean total and HDL cholesterol levels are based on all adults, regardless of fasting state,¹¹ examined during NHANES II (1976-1980), NHANES III (1988-1994), and NHANES 1999-2002. Estimates of mean LDL and triglyceride levels are based on adults who were examined in the morning and had fasted for 8.5 to 23 hours.¹¹ LDL cholesterol was calculated using the Friedewald equation (serum total cholesterol−HDL cholesterol−serum triglyceride/5) for examined persons with serum triglyceride levels of 400 mg/dL or less (≤4.52 mmol/L).²²

The overall response rates for adults aged 20 years or older on surveys before NHANES 1999-2002 ranged from 64% to 84%.^23- 25 The NHANES 1999-2002 data are based on 13 312 adults aged 20 years or older, of whom 10 291 (77.3%) were interviewed and 9471 (71.1%) were interviewed, underwent a physical examination, and were eligible for phlebotomy.

All lipid analyses were conducted on venous serum samples that were frozen and shipped on dry ice to the laboratory conducting the lipid analyses.²⁶ Methods for determining total cholesterol, HDL cholesterol, and triglyceride levels for surveys before NHANES 1999-2002 have been described.⁸ Total cholesterol, HDL cholesterol, and triglyceride measurements from each of the NHANES surveys were standardized according to the criteria of the CDC or the National Heart, Lung, and Blood Institute Lipid Standardization Program of the CDC.²⁷ For NHANES 1999-2002, the total cholesterol, HDL cholesterol, and triglyceride methods were calibrated using frozen serum calibration pools (Solomon Park Research Laboratories, Kirkland, Wash), which had CDC-assigned reference values.

In NHANES 1999-2002, total cholesterol, HDL cholesterol, and triglyceride methods were performed on an analyzer (Hitachi 704, Roche Diagnostics, Indianapolis, Ind) at the Johns Hopkins University Lipoprotein Analytical Laboratory, Baltimore, Md. Total cholesterol levels were measured using a coupled enzymatic reaction based on a method by Allain et al (Roche Diagnostics).²⁸ Triglyceride levels were measured using a coupled enzymatic reaction based on a method by Wahlefeld and Bergmeyer (Roche Diagnostics).²⁹ HDL cholesterol levels were measured using 2 methods. For the period 1999-2000, a Heparin-Manganese precipitation method was used for most samples.³⁰ A “direct” method of HDL cholesterol (Roche Diagnostics)^31- 32 was used for specimens with small sample volumes during 1999-2000 and for all samples collected during 2001-2002. For 1999-2002, total cholesterol, triglyceride, and direct HDL cholesterol levels met the National Cholesterol Education Program (NCEP) performance goals for precision and bias.^33- 35 Precipitated HDL cholesterol with a maximum precision of 4.5% and a bias up to 6.8% exceeded the NCEP performance goals for HDL cholesterol (4% for precision and 5% for bias). The HDL cholesterol was corrected for method bias for the NHANES 1999-2002 survey.^36- 37

Means and standard errors of the mean are presented for total, HDL, and LDL cholesterol values. Geometric means and standard errors of geometric means are presented for serum triglyceride levels because the distribution is highly skewed. Sample weights, which account for the differential probabilities of selection, nonresponse, and noncoverage are incorporated into the estimation process. Final examined sample weights were used for total and HDL cholesterol and morning fasting sample weights were used for triglyceride and LDL cholesterol levels.³⁸ The standard errors of the mean (or percentages) were estimated by Taylor Series Linearization,³⁹ a method that incorporates the sample weights and accounts for the sample design. Statistical hypotheses were tested at the α=.05 level of significance using a t statistic.⁴⁰ Multiple comparisons were performed by using the Bonferroni method.⁴¹ This method was applied by dividing .05 by number of implied comparisons. In testing for race/ethnicity differences in means, geometric means, and percentages, the overall level of .05 was divided by 3. For trends in serum total cholesterol level of adults aged 20 to 74 years during 1960-2002, there were 10 implied comparisons between any 2 of 5 surveys. For trends in LDL cholesterol, HDL cholesterol, and serum triglyceride levels during 1976-2002, there were 3 implied comparisons between any 2 of 3 surveys. All data analyses were performed by using the statistical packages SAS version 8.02 (SAS Institute, Cary, NC) and SUDAAN version 8 (RTI, Research Triangle Park, NC).

Sample sizes for the various lipid measurements are shown in Table 1 and the age-adjusted and age-specific means are presented in Table 2.^22,42 The effects of age on mean total cholesterol observed during NHES and previous NHANES surveys were also observed during 1999-2002. Mean total cholesterol levels increased with age through middle age and then decreased, reaching a peak at ages 50 to 59 years in men and 60 to 69 years in women. Men had higher total cholesterol levels than women for ages 30 to 49 years but lower levels after 60 years. Non-Hispanic black men had lower age-adjusted mean total cholesterol levels than either non-Hispanic white or Mexican American men. Mexican American women had lower age-adjusted mean total cholesterol levels than non-Hispanic white women.

As in previous NHANES surveys, the effects of age on mean LDL cholesterol levels were similar to those of mean total cholesterol. Men aged 30 to 49 years had higher mean LDL cholesterol levels than women of the same age, but women aged 70 years or older had higher mean LDL cholesterol levels than men of the same age. Non-Hispanic white and Mexican American but not non-Hispanic black men had higher age-adjusted mean LDL cholesterol levels than women had of similar race/ethnicity.

HDL cholesterol levels of women were consistently higher than those levels of men. Among men, non-Hispanic black men had higher HDL cholesterol levels than non-Hispanic white or Mexican American men. Among women, non-Hispanic black women and white women had higher HDL cholesterol levels than Mexican American women.

Serum triglyceride levels were lower in women than men among non-Hispanic black and non-Hispanic white but not Mexican American adults. In men, serum triglyceride levels were lower among non-Hispanic black men than non-Hispanic white or Mexican American men. Among women, triglyceride levels were lowest in non-Hispanic black women and highest in Mexican American women.

Trends in age-adjusted and age-specific mean serum total cholesterol levels of adults aged 20 to 74 years are presented for surveys 1960-1962 to 1999-2002, and values for adults aged 20 years or older are presented for NHANES III (1988-1994) and NHANES 1999-2002 (Table 3).⁴² Between 1960-1962 and 1999-2002, the age-adjusted mean total cholesterol levels of adults aged 20 to 74 years decreased from 222 mg/dL (5.75 mmol/L) to 203 mg/dL (5.26 mmol/L) in all adults (P<.001), from 220 mg/dL (5.70 mmol/L) to 203 mg/dL (5.26 mmol/L) in men (P<.001), and from 225 mg/dL (5.83 mmol/L) to 202 mg/dL (5.23 mmol/L) in women (P<.001). Mean total cholesterol levels decreased for each sex and age group except for men and women aged 20 to 29 years. Between 1960-1962 and 1988-1994 and between 1976-1980 and 1988-1994, the age-adjusted mean total cholesterol levels of adults aged 20 to 74 years decreased in all adults, in both men and women.^8- 9 Between 1988-1994 and 1999-2002, total cholesterol levels of adults aged 20 to 74 years did not decrease significantly in all adults (204 vs 203 mg/dL [5.28 vs 5.26 mmol/L]), in men (204 vs 203 mg/dL [5.28 vs 5.26 mmol/L]), or in women (205 vs 202 mg/dL [5.31 vs 5.23 mmol/L]).

With the availability of lipid data for adults 20 years or older for the first time in 1988-1984, trends in serum total cholesterol levels for adults 20 years or older between 1988-1994 and subsequent surveys are now possible. Between 1988-1994 and 1999-2002, the age-adjusted mean serum total cholesterol levels of adults 20 years or older decreased from 206 mg/dL (5.34 mmol/L) to 203 mg/dL (5.26 mmol/L) (P = .009) in all adults, did not decrease significantly in men (204 vs 202 mg/dL [5.28 vs 5.23 mmol/L]), and decreased from 207 mg/dL (5.36 mmol/L) to 204 mg/dL (5.28 mmol/L) in women (P=.009). Although the overall reductions in total cholesterol levels were modest, the decreases observed for men 60 years or older and for women 50 years or older were at least 10 mg/dL (≥0.26 mmol/L) and statistically significant.

Between 1960-1962 and 1999-2002, the mean serum total cholesterol level of men ages 60 to 74 years decreased by 28 mg/dL (0.73 mmol/L) (232 vs 204 mg/dL [6.01 vs 5.28 mmol/L]). During this same period, there was a 40-mg/dL (1.04 mmol/L) decrease for women ages 50 to 74 years (256 vs 216 mg/dL [6.63 vs 5.59 mmol/L] for women aged 50-59 years and 263 vs 223 mg/dL [6.81 vs 5.76 mmol/L] for women aged 60-74 years). Approximately one third of these reductions occurred between 1988-1994 and 1999-2002.

Age-adjusted mean serum total cholesterol levels for adults aged 20 years or older between 1988-1994 and 1999-2002 are compared by race/ethnicity and sex in Table 4.⁴² For Mexican American and non-Hispanic white individuals, age-adjusted mean total cholesterol levels decreased significantly in women only. For non-Hispanic black individuals, a significant decrease in serum total cholesterol between these 2 surveys was observed in both men and women.

The age-adjusted percentage of adults aged 20 years or older with a serum total cholesterol level of at least 240 mg/dL (≥6.22 mmol/L)¹¹ decreased from 20% (SE, 0.6) during 1988-1994 to 17% (SE, 0.6) during 1999-2002 (P<.001) (data not shown).⁴³

In Table 5,^22,42 age-adjusted and age-specific mean LDL cholesterol, HDL cholesterol, and serum triglyceride levels for adults aged 20 to 74 years are shown for the NHANES 1976-1980, 1988-1994, and 1999-2002 surveys, and for ages 20 years or older for the 1988-1994 and 1999-2002 surveys. Age-adjusted mean levels from the 2 most recent surveys are compared by race/ethnicity and sex. Between 1976-1980 and 1988-1994, age-adjusted mean LDL cholesterol levels decreased for all adults aged 20 to 74 years. In more recent years, LDL cholesterol levels further decreased between 1988-1994 and 1999-2002 for all adults aged 20 to 74 years, for men 20 to 74 years, for men 60 to 74 years, and for women 50 to 74 years but not for other sex and age groups.

Between 1988-1994 and 1999-2002, the age-adjusted mean LDL cholesterol level for adults aged 20 years or older decreased from 129 mg/dL (3.34 mmol/L) to 123 mg/dL (3.19 mmol/L) in all adults (P<.001), 131 mg/dL (3.39 mmol/L) to 126 mg/dL (3.26 mmol/L) in men (P=.005), and 126 mg/dL (3.26 mmol/L) to 120 mg/dL (3.11 mmol/L) in women (P<.001). Significant decreases were observed in the oldest age group (≥75 years) for both men and women as well as in men aged 60 to 74 years and in women aged 50 to 74 years. For ages 20 years or older, the age-adjusted mean LDL cholesterol levels for non-Hispanic white and non-Hispanic black adults decreased significantly between 1988-1994 and 1999-2002 for both men and women. For Mexican American adults, a significant decrease was observed only for women.

During the years 1976-2002, HDL cholesterol levels did not change significantly in men. In women, the age-adjusted mean HDL cholesterol level increased from 53.8 mg/dL (1.39 mmol/L) during 1976-1980 to 55.9 mg/dL (1.45 mmol/L) during 1999-2002 (P=.003). For women aged 60 to 74 years, the mean HDL cholesterol level increased from 1976-1980 to 1988-1994 (P=.01) and from 1988-1994 to 1999-2002 (P=.005). An increase of 3.5 mg/dL (0.09 mmol/L) in HDL cholesterol level between 1988-1994 and 1999-2002 was also observed in women aged 75 years or older (P=.008).

Age-adjusted geometric mean serum triglyceride levels in adults aged 20 to 74 years increased from 116 mg/dL (1.31 mmol/L) during 1988-1994 to 122 mg/dL (1.38 mmol/L) during 1999-2002 (P=.04). Between 1988-1994 and 1999-2002, the age-adjusted geometric mean serum triglyceride level among adults aged 20 years or older increased from 118 mg/dL (1.33 mmol/L) to 123 mg/dL (1.39 mmol/L), a difference that did not reach statistical significance (P = .06).

Data on lipid-lowering medications are presented for adults 20 years or older by sex and age and by sex and race/ethnicity for NHANES 1988-1994 and 1999-2002 in Table 6.^42,44 The age-adjusted percentage of adults 20 years or older on lipid-lowering medications increased from 3.4% in 1988-1994 to 9.3% in 1999-2002 (P<.001). A significant increase also occurred for each race/ethnicity and sex subgroup. The largest increase in the percentage of adults taking lipid-lowering medication between 1988-1994 and 1999-2002 occurred in the age group 60 years or older (6.8% to 24.3% in men and 8.7% to 21.6% in women). Also, during 1988-1994 and 1999-2002, the proportion of adults taking lipid-lowering medication was substantially higher in older adults (≥60 years) than in younger adults (20-39 years). Race/ethnicity differences in the percentage of adults taking lipid-lowering medications were observed during 1999-2002. In men, the age-adjusted percentage taking lipid-lowering medication was highest for non-Hispanic white men and lowest for Mexican American men. Among women, the age-adjusted percentage on lipid-lowering medication was higher in non-Hispanic white women than in non-Hispanic black women.

The age-adjusted mean total cholesterol level of adults 20 years or older decreased from 206 mg/dL (5.34 mmol/L) in 1988-1994 to 203 mg/dL (5.26 mmol/L) in 1999-2002 (P=.009) and the age-adjusted mean LDL cholesterol level decreased from 129 mg/dL (3.34 mmol/L) to 123 mg/dL (3.19 mmol/L) during this same period (P<.001). Significant and substantial declines in mean total and LDL cholesterol levels were observed in men 60 years or older and women 50 years or older but not in younger adults. In general, mean HDL cholesterol levels did not change during this period. The age-adjusted geometric mean serum triglyceride level of adults 20 years or older increased from 118 mg/dL (1.33 mmol/L) in 1988-1994 to 123 mg/dL (1.39 mmol/L) in 1999-2002 but was not statistically significant. The age-adjusted percentage of adults 20 years or older with serum total cholesterol level of at least 240 mg/dL (≥6.22 mmol/L) decreased from 20% to 17%, thereby achieving one of the Healthy People 2010 objectives (Objective 12-14).⁴⁵

It has previously been reported that serum total and LDL cholesterol levels among adults aged 20 to 74 years decreased from 1960-1962 to 1988-1994.^8- 9 Since 1994, these decreases have continued but only in men aged 60 to 74 years and women aged 50 to 74 years. The age-adjusted mean serum total cholesterol of adults aged 20 to 74 years did not change significantly between 1988-1994 and 1999-2002 (204 vs 203 mg/dL [5.28 vs 5.26 mmol/L]). However, the age-adjusted mean LDL cholesterol level decreased from 128 mg/dL (3.32 mmol/L) in 1988-1994 to 123 mg/dL (3.19 mmol/L) in 1999-2002 (P<.001).

The use of cholesterol-lowering medication is likely to have contributed to the decrease in total and LDL cholesterol observed predominantly in the older age groups. Between 1988-1994 and 1999-2002, a series of clinical trials with statins documented the benefit of cholesterol-lowering therapy.^{7- 8,46- 49} The medical community appears to have accepted the results and their implications for practice. Between 1995-1996 and 2001-2002, there was an increase in the number of physician office visits and hospital visits of men and women aged 45 years or older with statins prescribed (P<.001). Also, since the early 1990s, new categories of patients at high risk of CHD events have been identified including those patients with existing CHD or diabetes mellitus, and lower LDL cholesterol goals for such patients have been established to decrease their CHD risk more effectively.^11,50 Thus, it is not surprising that the increase in usage of cholesterol-lowering medications has occurred predominantly in older men and older women or that total and LDL cholesterol levels have continued to decrease in these age groups.

A number of other lifestyle factors have been shown to be related to lipid levels in adults, including dietary intake of saturated fat and cholesterol, excess weight, and level of physical activity.^11- 13 In both NHANES III and NHANES 1999-2002, data on these lifestyle factors as well as a broad spectrum of other health-related data were collected.

Between 1988-1994 and 1999-2002, the combined prevalence of overweight and obesity in adults aged 20 years or older increased from 55.9% to 65.1% and the prevalence of obesity increased from 22.9% to 30.4%.^51- 52 These increases could have contributed to the observed increase in mean triglyceride levels, which tend to be increased in overweight individuals.⁵³ Cross-sectional studies suggest that increases in total and LDL cholesterol are associated with increases in body mass index (calculated as weight in kilograms divided by the square of height in meters)^54- 55 and longitudinal studies suggest that increases in total cholesterol are also associated with increases in body mass index.^56- 57

The decrease in total and LDL cholesterol in adults between 1976-1980 and 1988-1994 was consistent with documented decreases in dietary intake of saturated fat and cholesterol.⁵⁸ Between 1988-1994 and 1999-2002, the age-adjusted mean saturated fat intake as a percentage of total calories for adults aged 20 years or older decreased slightly in men (11.3% to 10.8% kcal; P<.001) and in women (11.1% to 10.7% kcal; P=.006). The age-adjusted mean dietary cholesterol intake decreased by only 7 mg/d in men (346 to 339 mg/d) and increased by 11 mg/d in women (224 to 235 mg/d) (M.D.C., unpublished data, 2005).

The continued decrease of total and LDL cholesterol levels in older adults is a positive trend. Clinical trial results suggest that a 1% decrease in LDL cholesterol translates into a 1% decrease in relative risk for CHD.⁵⁹ Between 1988-1994 and 1999-2002, the use of cholesterol-lowering medication among older adults increased, although dietary data from NHANES 1999-2002 demonstrated only a small change in the overall intake of saturated fat or cholesterol. It appears that the decreases in total and LDL cholesterol may have been influenced more by increased medication use rather than by positive lifestyle changes. Increasing prevalence of obesity among adults^51- 52 may have contributed to a blunting in the decrease in total and LDL cholesterol levels, as reflected in the observed trend toward increased triglyceride levels. However, further research is needed to assess simultaneously the effects of lipid-lowering medications and other lifestyle factors on lipids. The National Heart, Lung, and Blood Institute’s NCEP recommends a healthy lifestyle, which includes reducing intake of saturated fat and cholesterol, achieving and maintaining healthy weight, and increasing physical activity for all adults,⁵⁰ and regards additional efforts to promote such lifestyle changes to be important for achieving further improvements in the population’s lipid levels. Additional analyses of these critical population lifestyle factors and lipid data are important. NHANES continues to monitor lipids and related lifestyle factors of CHD in the US adult population.