Prevalence and trends of Metabolic Syndrome in the adult US population, 1999–2010

Abstract

Objective

To characterize the prevalence of metabolic syndrome (MetS), its five components and their pharmacological treatment in US adults by gender and race over time.

Background

MetS is a constellation of clinical risk factors for cardiovascular disease, stroke, kidney disease and type 2 diabetes mellitus.

Methods

Prevalence estimates were estimated in adults (≥20 years) from the National Health and Nutrition Examination Survey (NHANES) from 1999–2010 (in 2-year survey waves). The biological thresholds, defined by the 2009 Joint Scientific Statement, were: (1) waist circumference ≥ 102 cm (males), and ≥ 88 cm (females) (2) fasting plasma glucose ≥100 mg/dl (3) blood pressure of ≥130/85 mm Hg (4) triglycerides ≥150 mg/dl (5) high-density lipoprotein-cholesterol (HDL-C) <40 mg/dl (males) and <50 mg/dl (females). Prescription drug use was estimated for lipid-modifying agents, anti-hypertensives, and anti-hyperglycemic medications.

Results

From 1999/2000 to 2009/10, the age-adjusted prevalence of MetS (based on biologic thresholds) decreased from 25.5% (95%CI: 22.5–28.6) to 22.9% (20.3–25.5). During this period, hypertriglyceridemia prevalence decreased (33.5% to 24.3%), as did elevated blood pressure (32.3% to 24.0%). The prevalence of hyperglycemia increased (12.9% to 19.9%), as did elevated waist circumference (45.4% to 56.1%). These trends varied considerably by gender and race/ethnicity groups. Decreases in elevated blood pressure, suboptimal triglycerides and HDL-C prevalence have corresponded with increases in anti-hypertensive and lipid-modifying drugs, respectively.

Conclusion

The increasing prevalence of abdominal obesity, particularly among females, highlights the urgency of addressing abdominal obesity as a healthcare priority. The use of therapies for MetS components aligns with favorable trends in their prevalence.

Introduction

In this manuscript we examine trends in the prevalence of metabolic syndrome (MetS), its five components, and their pharmacological treatment in United States adults by gender and race from 1999/2000 to 2009/10. MetS, defined by a constellation of clinical criteria, is utilized to identify patients at increased risk for cardiovascular disease (CVD), type II diabetes mellitus (T2DM), and all-cause mortality (1–4). The integrated epidemiological concept of MetS originated from the observation that several metabolic risk factors often co-occur in patients at high risk of CVD, namely abdominal obesity, dyslipidemia, elevated blood pressure, impaired fasting glucose, and insulin resistance (5). The risk factors that comprise MetS are independently associated with CVD and T2DM and have become the therapeutic targets of lifestyle modification, medications, and surgical interventions (6). Further, there is evidence that MetS is an effective and simple clinical tool for identifying high-risk subjects predisposed to CVD and T2DM (7). While these targets have been in place for over a decade, US trends of MetS prevalence in the overall population and across gender and race/ethnic groups have not been characterized. The primary objectives of this manuscript are (a) to examine trends in the prevalence of MetS, its components and the pharmacological treatments used to control these components in the adult US population between 1999–2010, and (b) to compare time trends in these risk factors by race/ethnicity and gender.

Methods

We used data from the National Health and Nutrition Examination Survey (NHANES) representative of the civilian, non-institutionalized US population (8). NHANES is a series of cross-sectional, national, stratified, multistage probability surveys of the civilian, non-institutionalized US population conducted by The Centers for Disease Control and Prevention. Beginning in 1999, NHANES became a continuous program with two-year cycles meant to provide national estimates of the US population. Participants were recruited using a multistage, stratified sampling design consisting of four stages of selection: (i) counties or small groups of contiguous counties; (ii) a block or group of blocks containing a cluster of households; (iii) households; and (iv) one or more participants from households. Because of the differential probabilities of selection, sampling weights were created that reflected the base probabilities of selection, adjustment for non-response, and post-stratification. All adults provided written informed consent; the study was approved by the National Center for Health Statistics Institutional/Ethics Review Board. This analysis was reviewed by University of Pennsylvania Institutional Review Board and was considered exempt from full review.

Our study data were collected in six 2-year cycles from 1999/2000 to 2009/2010. We included individuals aged 20 or older who self reported as Mexican-American (MA), Non-MA White, or Non-MA Black who fasted for 8 hours or more and had complete information on the relevant variables of interest (e.g., glucose, HDL-C, triglycerides, blood pressure and waist circumference). We excluded individuals who did not fulfill the fasting criteria and those whose fasting status was unknown leading to a final analytic sample with the following individuals: 1,613 in 1999/2000; 1,908 in 2001/2002; 1,687 in 2003/2004; 1,703 in 2005/2006; 1,869 in 2007/2008; and 2,034 in 2009/2010 (Appendix Tables E1, E2). A technical appendix provided in the Online Data Supplement (ODS) describes in detail the data, sample selection, and methods used to estimate all components of the syndrome and other aspects of the analysis (eMethods).

Briefly, MetS was estimated using criteria consistent with the most recent harmonized definition of MetS published in 2009 (Table 1) (3,9). Patients who met three or more of the criteria were defined as having MetS. Waist circumference was measured at the high point of the iliac crest at minimal respiration to the nearest 0.1 cm. Serum triglyceride concentrations were measured enzymatically after hydrolyzation to glycerol, and HDL-C was measured following the precipitation of other lipoproteins with a heparin–manganese chloride mixture. Plasma glucose concentrations were determined using an enzymatic reaction. Up to four attempts were made to collect three blood pressure readings in the mobile examination center; the average of all available measures was used. Race/ethnicity was determined by self-reported survey responses, and categorized as non-Mexican-Americans white, non-Mexican-Americans black, and Mexican-American.

Table 1.

Components of the Metabolic Syndrome

Component	Term	Defined Cut-Off
Elevated waist circumference	Abdominal Obesity	≥ 102 cm for males, and ≥ 88 cm for females in the United States (US)(11)
Elevated blood pressure	Hypertension	Systolic BP ≥130 mm Hg, diastolic BP ≥85 mm Hg or antihypertensive drug treatment in a patient with history of hypertension
Elevated Triglycerides	Dyslipidemia	Triglycerides ≥150 mg/dl or drug treatment for elevated triglycerides
Low HDL-C	Dyslipidemia	HDL-C <40 mg/dl in men or <50 mg/dl in women or drug treatment for reduced HDL-C
Elevated fasting plasma glucose	Hyperglycemia	≥100 mg/dl or drug treatment for elevated glucose

^*The presence of any 3 of 5 components results in a diagnosis of the metabolic syndrome.

Source: 2009 Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity (3)

To complement the trends analysis in the clinical (biological) thresholds of the MetS we also estimated the age-adjusted prevalence of the use of each of the following prescription drug classes: (1) lipid-modifying agents, (2) anti-hypertensive and (3) anti-hyperglycemic medications. While the Joint Scientific Statement (3) classifies use of these agents as an equal criterion for meeting the definition of specific components (e.g., using anti-hypertensive medication is equal to being hypertensive), medication use in NHANES is coded based on the therapeutic indication of the attendant generic drug code, thus the true indication is unknown. While NHANES collects information on self-reported use of medication for high blood pressure and glucose, such information is not available for lipid medication. As lipid-modifying agents (e.g., HMG CoA reductase inhibitors or fibric acids derivatives) can both increase HDL-C and lower triglyceride levels (10,11) we chose to focus on trends in classes of drugs rather than make assumptions on therapeutic indication that might lead to overestimates of MetS. The interview weight was used for trends in medications. A list of the medications used and their therapeutic indicators are provided in the ODS.

We age standardized prevalence estimates through the direct method using the 2000 US population as the standard (see eMethods for detailed summary of the statistical methods). This allows examination of the prevalence of MetS and its components over time. For time-trend analysis our primary outcome was the prevalence rate of change per year from survey wave 1 (1999–2000) to survey wave 6 (2009–2010). We employed two modeling strategies, both age-adjusted, by fitting separate models for each gender and race/ethnicity group for MetS and its individual components. First, we modeled the likelihood that an individual had MetS or met each of the MetS components using logistic regression. Second, we estimated MetS prevalence as the ratio of the number of cases over the total population using a Poisson model. All models were age-adjusted and the direction and significance level for both model specifications were qualitatively equivalent. Statistical analyses accounted for the complex sampling design, non-response, differential sampling, and non-coverage as recommended by the NHANES statistical documentation. The NHANES morning fasting sample weight was used for all MetS and its component-specific prevalence estimates.

Results

Approximately a fifth of the adult US population remains at high cardiometabolic risk (Table 2). From 1999/2000 to 2009/10, the age-adjusted prevalence of MetS (based on biologic thresholds) decreased from 25.5% [95%CI: 22.5–28.6] to 22.9% [95% CI: 20.3–25.5) (p^trend =0.024). Mexican-Americans, particularly females, have a higher MetS prevalence than other subgroups.

Table 2.

Age-standardized prevalence of the Metabolic Syndrome in the United States, 1999–2010

Total Population
	1999–2000	2001–2002	2003–2004	2005–2006	2007–2008	2009–2010	ptrend
Metabolic Syndrome
Total Population	25.54% (22.49–28.58)	27.37% (25.25–29.50)	25.76% (22.98–28.53)	23.18% (20.22–26.15)	24.94% (21.46–28.42)	22.90% (20.28–25.53)	0.024
Males	23.35% (18.04–28.65)	27.45% (23.96–30.94)	25.26% (20.50–30.02)	24.57% (20.78–28.35)	26.54% (23.57–29.50)	23.69% (18.79–28.58)	0.54
Females	27.50% (24.49–30.50)	26.98% (24.54–29.42)	26.20% (22.05–30.35)	22.10% (18.19–26.01)	23.54% (18.69–28.38)	21.80% (19.04–24.56)	0.005
Waist Circumference
Total Population	45.35% (40.66–50.04)	48.96% (46.18–51.74)	55.35% (52.29–58.41)	54.24% (50.64–57.84)	53.78% (50.60–56.95)	56.07% (52.79–59.35)	<0.001
Males	36.48% (30.55–42.41)	39.82% (35.30–44.33)	46.02% (41.52–50.51)	46.41% (42.17–50.64)	45.44% (41.88–49.01)	46.44% (41.22–51.66)	0.011
Females	53.53% (48.55–58.51)	57.67% (53.59–61.75)	64.41% (60.03–68.79)	61.70% (56.80–66.60)	61.93% (56.82–67.04)	65.38% (62.36–68.39)	<0.001
Blood Pressure
Total Population	32.30% (29.00–35.61)	34.69% (31.60–37.77)	30.56% (27.35–33.78)	30.44% (27.80–33.08)	24.25% (22.28–26.21)	24.04% (20.91–27.18)	<0.001
Males	35.22% (30.66–39.78)	37.21% (31.93–42.50)	34.64% (29.74–39.54)	33.95% (30.75–37.16)	25.18% (22.21–28.15)	27.84% (23.99–31.69)	<0.001
Females	29.28% (25.99–32.56)	32.15% (29.33–34.98)	26.42% (23.24–29.59)	27.27% (23.39–31.15)	22.80% (20.15–25.45)	20.19% (17.02–23.36)	<0.001
Triglycerides
Total Population	33.53% (29.76–37.30)	33.32% (31.22–35.41)	32.37% (28.97–35.77)	30.20% (26.84–33.56)	28.84% (26.12–31.56)	24.25% (21.57–26.93)	<0.001
Males	35.04% (28.17–41.91)	37.85% (33.50–42.21)	36.06% (31.01–41.10)	35.45% (31.24–39.67)	34.71% (30.88–38.55)	26.26% (21.89–30.62)	0.004
Females	32.03% (28.17–35.90)	28.54% (26.78–30.30)	28.50% (24.74–32.25)	25.24% (21.83–28.66)	23.56% (19.84–27.28)	21.74% (17.76–25.71)	<0.001
HDL-C
Total Population	38.51% (33.56–43.46)	33.86% (31.13–36.59)	27.50% (24.60–30.39)	21.33% (19.05–23.62)	28.30% (24.21–32.40)	30.05% (26.93–33.16)	<0.001
Males	35.56% (29.59–41.53)	31.57% (27.72–35.43)	22.49% (16.86–28.12)	20.61% (17.52–23.70)	27.28% (23.72–30.85)	27.91% (23.81–32.01)	0.004
Females	41.04% (35.14–46.93)	35.97% (32.99–38.96)	32.48% (27.09–37.87)	22.16% (18.89–25.43)	29.30% (23.83–34.78)	32.00% (28.69–35.30)	<0.001
Glucose
Total Population	12.94% (9.84–16.04)	15.62% (13.58–17.66)	14.15% (12.53–15.76)	17.89% (15.34–20.44)	22.82% (19.71–25.94)	19.92% (16.38–23.47)	<0.001
Males	16.44% (12.17–20.70)	18.77% (15.26–22.27)	17.76% (15.22–20.30)	20.54% (16.45–24.62)	28.64% (24.31–32.97)	25.01% (20.10–29.92)	<0.001
Females	10.05% (7.85–12.25)	12.58% (11.12–14.05)	10.41% (8.17–12.66)	15.60% (12.45–18.75)	17.46% (13.51–21.40)	15.14% (11.98–18.30)	<0.001

S=not significant, p > 0.05

While the prevalence of MetS has declined in the total population when measuring clinical targets, there is a divergence in trends for its individual components, mainly in high waist circumference for the total population and among the gender and race/ethnic groups (Figure 1). For example, the prevalence of abdominal obesity for the total population increased from 45.4% [95% CI: 40.7–50.0%] in 1999/2000 to 56.1% [CI: 52.8–59.4%] in 2009/2010. Of note baseline rates of abdominal obesity were much higher among females than males, particularly among Mexican-Americans (eTables 4–6). Estimates of elevated blood pressure for the total population declined over time from 32.3% [29.0–35.6] in 1999/2000 to 24.0% [20.9–27.1] (p^trend < 0.001) in 2009/2010 (Table 2). Among males, only non-Mexican-American whites experienced a decline in elevated blood pressure, while among females, both non-Mexican-American whites and Mexican-Americans showed a decline. This reduction aligns with increased awareness and pharmacological treatment of elevated blood pressure (Figure 2). The prevalence of hypertriglyceridemia also declined in the total population over the study period, from 33.5% [29.8–37.3] to 24.3% [21.6–26.9] (p^trend < 0.001). Similar to elevated blood pressure, all racial/ethnic groups experienced a decline in elevated triglycerides except for Non-Mexican-American blacks (eTables 4–6), although the latter group showed the lowest baseline prevalence of hypertriglyceridemia (Figure 2). During the same time period the use of lipid-modifying agents rose from 8% [7.3–8.7%] to 15.6% [14.6–16.5] in the total NHANES sample. A similar trend in greater use of lipid-modifying agents was observed among all of the population subgroups. While some of the variability in HDL-C trends between 2001–2006 is likely attributable to a change in the laboratory assay during this time period(12), there was an overall decline in sub-optimal HDL-C in the total population from 38.5% [33.6–43.5] in 1999/2000 to 30.1% [29.9–33.2] in 2009/2010 (p^trend < 0.001). All racial/ethnic groups experienced a decline in the prevalence of sub-optimal HDL-C over time (eTable 4), except for Non-Mexican-American black males (eTable 5). In contrast to the reduced prevalence of other MetS components, the prevalence of hyperglycemia rose in the total population from 12.9% [95% CI: 9.8–16.0%] in 1999/2000 to 19.9% [95% CI: 16.4–23.5%] in 2009/2010 (p^trend < 0.001) (Table 2), with Mexican-American males experienced the fastest increase among all subgroups of the population

Figure 1. Prevalence and trends of the five components of Metabolic Syndrome in the adult US population, 1999–2010.

Prevalence and trends of the components of Metabolic Syndrome for US adults aged 20 or older for the total population by sex (first column), by race (second column), and by race and sex (third and fourth columns). Waist circumf.= waist circumference; HDL-C= high-density lipoprotein cholesterol; Non-Mex-Am= Non-Mexican American. Table 1 shows the cut-offs defined as high risk for each indicator. Shaded areas represent 95% confidence intervals.

Figure 2.

Prevalence and trends of prescription drug use related to components of Metabolic Syndrome in the adult US population, 1999–2010

Prescription drug use related to components of Metabolic Syndrome for US adults aged 20 or older for the total population by sex (first column), by race (second column), and by race and sex (third and fourth columns). Non-Mex-Am= Non-Mexican American. The online data supplement Table E7 shows the specific medications included as anti-hypertensive, lipid modifying agents, and anti-hyperglycemic. Shaded areas represent 95% confidence intervals.

Comment

We found that the prevalence of MetS has declined slightly when measured on the basis of clinical targets using the biological thresholds outlined in ATP-3 (10,11) and the Joint Scientific Statement (3). Yet, even with this decline about one-fifth of the adult US population would be classified as having MetS, living with suboptimal measures for at least three of the five MetS components. These results indicate a limited decline in the prevalence of MetS in the past decade. Our results are consistent with an earlier analysis of NHANES III (1988–94) that used similar ATP III criteria to define MetS and found that approximately 22% of US adults (24% after age adjustment) had MetS, with similar gender and race/ethnicity patterning (13).

The MetS is an epidemiological construct of different permutations of risk factors, each with unique clinical implications and treatment strategies (14). Understanding the trends in the population’s burden of MetS is valuable given the recognition that certain cardiometabolic risk factors tend to co-exist. There is evidence suggesting that specific clusters of 3 or more MetS factors are not necessarily associated with greater risk for CVD outcomes and that fasting glucose is the main predictor of T2DM (15). However, it is important to identify the population with MetS because these individuals have a particularly adverse metabolic state that warrants aggressive intervention for specific traits. For example, results from the Framingham Study indicate that trait combinations that did not include fasting glucose also imparted an increased risk for incident T2DM (15). Increasing awareness of MetS may also account for some of the declines in its component risk factors. For instance, in our analysis and in previous evidence of time trends in MetS components, there has been a decline in average lipid levels among US adults from 1960–2006, which has largely been attributed to the growing proportion of the population receiving lipid-lowering medication (16,17). Perhaps the successes we have observed in lipid management are partly due to increasing clinical recognition of the importance of screening for this variable in the presence of abdominal obesity, for example, as both are components of MetS. In the current analysis, MetS components had divergent trends. We observed pronounced declines in dyslipidemia, specifically in hypertriglyceridemia, results that align with previous studies (18). Concurrent with improvements in dyslipidemia, we observed higher utilization of drugs over time that target suboptimal lipid profiles such as statins, fibrates, and niacin derivatives (Figure 2). Indeed, favorable trends in blood pressure and dyslipidemia may reflect increasing availability and utilization of pharmacologic interventions. This is in contrast to our observations on the increasing trend of abdominal obesity, most pronounced in females, which may identify a population at potentially high cardiometabolic risk. Particularly important are the sex and racial/ethnic differences in the prevalence of increased waist circumference. White males are more likely to have high abdominal obesity than their counterparts of other race/ethnicity, but the opposite is true among females. These results suggest the need to have different weighting of MetS components depending on patient’s ethnicity rather than having a harmonized definition for all racial/ethnic groups.

Also notable are the sex and racial/ethnic differences in the prevalence of individual MetS components. We found that white males are more likely to have abdominal obesity than their counterparts of other race/ethnicity, but the opposite is true among females. We also found that Non-Mexican-American black males and females consistently had higher prevalence of elevated blood pressure than other groups but they showed the lowest dyslipidemia prevalence levels. Additionally, Mexican-Americans, both overall and by gender, consistently had higher prevalence of low HDL-C, high triglycerides, and high blood glucose than other subgroups.

There are limitations to our study. The divergent trends we observed in MetS components suggest that multitudes of factors, in addition to known risk factors, affect cardiometabolic risk. These may include socioeconomic status and regional differences in access to care, which we did not measure in our analysis. Also, trends in HDL-C may be underestimated due to variations in the assay during the study period (12). NHANES provides adjusted estimates for effected survey waves that exceeds the maximum allowable bias, but these changes are known to be responsible for secondary variation in point estimates across the six waves (12). A more detailed examination of these changes and their impact on the measurement of HDL-C has been published previously (16,17). In addition, conclusions that are based on strict cut-offs limit our understanding of individuals who are near the cut-off points and may have risks similar to subjects with MetS, but do not classify as meeting a certain risk factor (19,20). The cut-points for elevated waist circumference are not well defined, particularly for subjects of non-European ethnicity. It remains unclear whether the same criteria for abdominal obesity should be applied to individuals of a particular ethnic group regardless of their country of residence/origin (3). The most recent harmonized definition of MetS has consistent cut-offs for all risk factors, but recommends that the cut-off values for abdominal obesity be selected based on the study or population being examined (3). In the current analyses we imposed the US cut-offs (11) on all NHANES respondents, consistent with the methods of previous studies (13). Given that the US cut-offs are the most generous for defining abdominal obesity (≥ 102 cm for males and ≥ 88 cm for females), as compared to potentially choosing the lower Latin American or African cutoffs based on ancestry for racial and ethnic sub-groups, our estimates of the burden of abdominal obesity may in fact be conservative. Also, as the use of self-reported race/ethnicity is susceptible to misclassification bias the NHANES sampling strategy might be responsible for fluctuations and variation between the prevalence estimates in survey waves. A final limitation of this work is that while it demonstrates MetS trends it does not show how these trends correlate with trends in clinically significant outcomes such as cardiovascular morbidity and mortality. However, our observation of divergent trends in metabolic syndrome components is important evidence of the ongoing burdens of risk for cardiovascular disease in the US, and suggests that priority should be placed in addressing those risk factors that have increased in prevalence over the past decade (ie obesity and hyperglycemia) (4,5,9,10).

In sum, our analysis examined the patterns of MetS across six waves of NHANES between 1999–2010 and showed that while the prevalence of MetS as it is currently defined has declined slightly over time, there have been population-level changes in its components. Most striking is the upward trend in abdominal obesity across the entire US population. Insulin resistance also appears to be on the rise. However, there is a downward trend in elevated triglycerides with a current overall prevalence near 25% likely corresponding with increased use of statins and other lipid-modifying agents. Evidence of underlying divergent trends in cardiometabolic risk in the adult US population has also revealed an alarming increase in abdominal obesity since 1999, despite apparently stable prevalence of MetS during the same time period. Our results demonstrate potential targets for interventions to reduce the future burden of CVD and T2DM, and confirm the urgent need for multi-faceted and coordinated treatment programs to address the increasing prevalence of obesity in the US.

Abbreviations

MetS

metabolic syndrome

CVD

cardiovascular disease

T2DM

type II diabetes mellitus

NHANES

National Health and Nutrition Examination Survey

MA

Mexican-American

HDL-C

high-density lipoprotein cholesterol

ODS

Online Data Supplement

CI

confidence interval