Waist Circumference and Metabolic Syndrome: The Risk for Silent Coronary Artery Disease in Males

Abstract

Background:

Waist circumference (WC) is a component used to define metabolic syndrome. However, its role as an independent predictor of silent coronary artery disease (CAD), above its contribution to metabolic syndrome, remains unknown.

Methods:

Male veterans without known CAD, undergoing cardiac stress testing for indications other than typical angina or its equivalent, were evaluated for the presence of silent CAD. High WC and metabolic syndrome were defined per the revised National Cholesterol Education Program (NCEP-R) and the International Diabetes Federation (IDF) criteria.

Results:

Data on 1,071 patients (age 61±11 years) were analyzed retrospectively. On multivariable logistic regression analysis [odds ratio (OR), 95% confidence interval (CI), P value), a WC ≥94 cm (1.42, 1.04–1.93; P=0.026), metabolic syndrome by NCEP-R (1.73, 1.29–2.33; P<0.0001), and metabolic syndrome by IDF (1.57, 1.17–2.11; P=0.003) were independent predictors of silent CAD. When comparing patients meeting criteria for metabolic syndrome defined by either NCEP-R or IDF, the prevalence of silent CAD was not statistically different (P=0.86). The prevalence of silent CAD associated with a high WC was not inferior to that seen between silent CAD and metabolic syndrome as defined by either criterion. Last, among patients with metabolic syndrome defined by NCEP-R, those with a high WC as a defining component of metabolic syndrome had a higher prevalence of silent CAD (30% vs. 20%; P=0.026).

Conclusion:

A WC ≥94 cm in males is independently associated with an increased prevalence of silent CAD. In patients with metabolic syndrome, this prevalence is increased by the presence of high WC.

Introduction

S ilent coronary artery disease (CAD) is defined as the presence of myocardial ischemia or infarct in the absence of angina or anginal equivalents.¹ In spite of being the most common manifestation of CAD,^2,3 no screening guidelines exist to determine its burden in patients with traditional risk factors for coronary atherosclerosis. Cardiac stress testing can provide reliable diagnostic information on the burden of stable CAD and reversible ischemia in these patients.

Over the years, there has been a steady rise in the prevalence of metabolic syndrome⁴ and abdominal obesity.⁵ Various organizations, such as the National Cholesterol Education Program (NCEP),^6,7 the International Diabetes Federation (IDF),⁸ and the World Health Organization (WHO),⁹ have published different criteria to define metabolic syndrome. It has been proposed that individual components of metabolic syndrome interact synergistically to cause or accelerate atherosclerosis.¹⁰ However, multiple questions have been raised in the recent past regarding the reliability and utility of a diagnosis of metabolic syndrome, as compared to its components, to determine risk for CAD^11

–15 or silent CAD.¹⁶

It has been recently shown that a high waist circumference (WC), and thus abdominal obesity, is a greater risk factor for cardiovascular disease (CVD) than general obesity.^17

–20 In addition, abdominal obesity has been shown to be strongly associated with metabolic syndrome.^18,19,21 Although different values (≥94 cm vs. >102 cm) have been used in the past for defining a high WC, these data currently lack scientific rationale. Lakka et al. demonstrated an increase in all-cause mortality in men with metabolic syndrome using a defined high WC of >102 cm rather than ≥94 cm.²² However, there is still a large segment of the population with a WC <94 cm that continues to remain at an increased cardiovascular risk due to the presence of multiple other risk factors.²¹ In fact, there have been differences amongst various study populations showing inconsistency in the association between abdominal obesity and its correlated metabolic derangements in predicting overall cardiovascular risk.^23
–25

Considering these differences, we sought to determine the importance of using a high WC as an independent tool to identify patients at increased risk for silent CAD, and the true contribution of high WC to CVD risk among patients with metabolic syndrome.

Methods

Study population

After approval from the institutional review board, a retrospective review of consecutive cardiac stress tests from 2004 to 2006 at a university affiliated veterans-affairs hospital was done. Male veterans ≥18 years of age, undergoing either a myocardial perfusion single-photon emission computed tomography (SPECT) or two dimensional (2-D) stress echocardiography, were included in the study. Indications for cardiac stress testing included nonanginal chest pain (42%), preoperative cardiac evaluation (20.1%), cardiac arrhythmias (1.2%), evaluation for new-onset heart failure with left ventricular systolic dysfunction (17.9%), palpitations and syncope (4%), risk stratification due to presence of cardiovascular risk factors (12.1%), and nonspecific changes on electrocardiogram (ECG) (2.6%). Patients with known CAD and those presenting with symptoms of definite or probable angina,²⁶ were excluded. In addition, patients who underwent ECGstress testing without imaging data were excluded. Last, patients with submaximal exercise stress tests were also excluded, unless they subsequently underwent other forms of chemical (dobutamine or adenosine) stress testing.

Stress testing protocols

All patients underwent either a myocardial perfusion SPECT (treadmill, dobutamine, or adenosine), or 2-D stress echocardiography (treadmill or dobutamine). As described previously, standard methods and protocols for stress testing for transthoracic exercise echocardiography, dobutamine stress echocardiography, and stress myocardial perfusion SPECT were used in our study.¹³

Data collection

All data were collected retrospectively by a systematic review of medical records and stored on a secure server with unique patient identifiers removed. WC was recorded at the time of stress testing and was measured at the level of the umbilicus with participants in standing position. Blood pressure was obtained with a mercury sphygmomanometer with the participant in a supine position prior to stress testing. Laboratory analyses of fasting blood samples assayed using automated techniques at the Veterans Affairs Medical Center Laboratory provided the concentrations of triglycerides, high-density lipoprotein cholesterol (HDL-C), and blood glucose.

Definitions

The revised National Cholesterol Education Program (NCEP-R) and the IDF criteria were both used to define metabolic syndrome. Two definitions for high WC (>102 cm and ≥94 cm) were used. As per the NCEP-R, metabolic syndrome was defined as the presence of at least three of the following five risk factors: A high WC (>102 cm), elevated blood pressure (≥130/85 mmHg or on treatment), insulin resistance (fasting plasma glucose of ≥100 mg/dL), low HDL-C (<40 mg/dL), and/or high serum triglycerides (≥150 mg/dL). As per the IDF, metabolic syndrome was defined as the presence of a high WC (≥94 cm) along with at least two of the four additional risk factors: Elevated blood pressure (≥130/85 mmHg or on treatment), insulin resistance (fasting plasma glucose of ≥100 mg/dL), low HDL-C (<40 mg/dL), and/or high serum triglycerides (≥150 mg/dL).

Silent CAD was defined as the presence of reversible and/or irreversible perfusion defects on SPECT or, resting and/or stress-induced wall motion abnormalities on 2-D echocardiography. Nonanginal chest pain was defined as reproducible and/or pleuritic pain that was not associated with exertion or ECG changes, or altered with sublingual nitroglycerine. Stress echocardiography studies were interpreted and confirmed by board-certified cardiologists, and SPECT studies were interpreted and confirmed by board-certified radiologists at the Veterans Affairs Medical Center.

Statistical analysis

Statistical analyses were conducted using STATA 10.1 (College Station, TX). The Student t-test was used to analyze differences in continuous data, and the chi-squared test was used to determine the differences between proportions of categorical data. Univariate logistic regression analyses were performed to identify the associations between silent CAD and clinically significant variables. Only those variables having a significant association with silent CAD on univariate models were included in the multivariate models. Multivariate logistic regression analyses were performed using a stepwise forward selection approach including variables with a P value <0.05. Because metabolic syndrome was observed to have significant collinearity with WC and high triglyceride levels, separate regression analyses were performed with metabolic syndrome in one model and WC and high triglycerides in a separate model.

Results

Of the 2,750 patients undergoing cardiac stress testing, 1,071 male veterans (84% Caucasians, n=900) met inclusion criteria. The mean patient age was 61±11 years. Demographic data for the study population is shown in Table 1. SPECT or stress echocardiography was performed on 742 (69.3%) and 329 (30.7%) patients, respectively. A total of 232 (21.7%) patients met criteria for silent CAD on stress imaging. Significant univariate predictors of silent CAD are shown in Table 2. Significant multivariate predictors of silent CAD using different defining values for a high WC and different defining criteria for metabolic syndrome are shown in Tables 3 and 4.

Table 1.

Patient Demographics (N=1071)

	Silent CAD (n=232)	No silent CAD (n=839)	P
Age (years), mean±SD	63+10	61+11	0.0007
Caucasian race	206 (88.8%)	694 (82.7%)	0.03
Hypertension	153 (66.0%)	558 (66.5%)	0.87
Diabetes mellitus	95 (41.0%)	282 (33.6%)	0.04
Hyperlipidemia	163 (70.3%)	563 (67.1%)	0.36
Smoking history	100 (43.1%)	328 (39.1%)	0.27
Family history of CAD	86 (37.1%)	343 (40.9%)	0.29
Metabolic syndrome NCEP-R	126 (54.3%)	347 (41.4%)	0.0001
Metabolic syndrome IDF	116 (50.0%)	328 (39.1%)	0.003
WC (>102 cm)	110 (47.4%)	299 (35.6%)	0.001
WC (>94 cm)	148 (63.8%)	458 (54.6%)	0.012
Triglycerides (≥150 mg/dL)	105 (45.3%)	312 (37.2%)	0.03
HDL-C (<40 mg/dL)	87 (37.5%)	261 (31.1%)	0.07

CAD, coronary artery disease; SD, standard deviation; NCEP-R, revised National Cholesterol Education Program; IDF, International Diabetes Federation; WC, waist circumference; HDL-C, high-density lipoprotein cholesterol.

Table 2.

Univariable Predictors of Silent Coronary Artery Disease

	OR	95% CI	P
Age quartiles (range), years^a
Q1 (22–54)	Ref	Ref
Q2 (55–60)	1.59	1.02–2.48	0.04
Q3 (61–69)	1.93	1.24–3.01	0.004
Q4 (>70)	2.32	1.50–3.58	<0.0001
Caucasian race	1.65	1.05–2.56	0.025
Diabetes mellitus	1.37	1.02–1.85	0.04
Hypertension	0.98	0.72–1.33	0.87
Smoking history	1.18	0.88–1.58	0.27
Hyperlipidemia	1.74	1.04–2.90	0.36
Family history of coronary artery disease	0.85	0.63–1.15	0.29
Metabolic syndrome NCEP-R	1.69	1.26–2.26	<0.0001
Metabolic syndrome IDF	1.56	1.16–2.09	0.003
WC (>102 cm)	1.63	1.21–2.18	0.001
WC (>94 cm)	1.47	1.09–1.98	0.012
Triglycerides (≥150 mg/dL)	1.40	1.04–1.87	0.026
HDL-C (<40 mg/dL)	1.33	0.98–1.80	0.07

Overall P value for age <0.0001.

OR, odds ratio; CI, confidence interval; Ref, reference group; NCEP-R, revised National Cholesterol Education Program; IDF, International Diabetes Federation; WC, waist circumference; HDL-C, high density lipoprotein cholesterol.

Table 3.

Multivariate Predictors of Silent CAD Using NCEP-R Criterion for Metabolic Syndrome and Waist Circumference Cutoff of >102 cm

	Multivariable ^a			Multivariable ^b
	OR	95% CI	P	OR	95% CI	P
Age quartiles (range), years^c
Q1 (22–54)	Ref	Ref		Ref	Ref
Q2 (55–60)	1.60	1.03–2.50	0.038	1.59	1.02–2.48	0.04
Q3 (61–69)	1.90	1.22–2.97	0.005	1.95	1.24–3.05	0.004
Q4 (>70)	2.44	1.57–3.78	<0.0001	2.54	1.63–3.94	<0.001
WC (>102 cm)				1.60	1.18–2.16	0.002
Triglycerides (≥150mg/dl)				1.41	1.04–1.91	0.03
Metabolic syndrome NCEP-R	1.73	1.29–2.33	<0.0001

Excludes WC and triglycerides.

Excludes metabolic syndrome.

Overall P value for age <0.0001.

OR, odds ratio; CI, confidence interval; Ref, reference group; WC, waist circumference; NCEP-R, revised National Cholesterol Education Program.

Table 4.

Multivariate Predictors of Silent Coronary Artery Disease Using International Diabetes Federation Criterion for Metabolic Syndrome and Waist Circumference Cutoff of ≥94 cm

	Multivariable ^a			Multivariable ^b
	OR	95% CI	P	OR	95% CI	P
Age quartiles (range), years^c
Q1 (22–54)	Ref	Ref		Ref	Ref
Q2 (55–60)	1.54	0.99–2.40	0.058	1.58	1.01–2.46	0.045
Q3 (61–69)	1.89	1.21–2.95	0.005	1.91	1.22–2.98	0.005
Q4 (>70)	2.36	1.52–3.63	<0.0001	2.53	1.63–3.93	<0.0001
WC (>94 cm)				1.42	1.04–1.93	0.026
Triglycerides (≥150mg/dL)				1.42	1.05–1.93	0.025
Metabolic syndrome IDF	1.57	1.17–2.11	0.003

Excludes WC and triglycerides,

Excludes metabolic syndrome.

Overall P value for age <0.0001.

OR, odds ratio; CI, confidence interval; WC, waist circumference; Ref, reference group; IDF, International Diabetes Federation.

Among all patients, 409 (38.2%) had a WC >102 cm and 606 (56.6%) had a WC ≥94 cm. Metabolic syndrome was present in 473 (44.2%) and 444 (41.5%) patients as defined by the NCEP-R and the IDF criteria, respectively. Using the NCEP-R criterion, the overall prevalence of a high WC (>102 cm) in patients with metabolic syndrome was 66% compared to 16% in patients without metabolic syndrome (P<0.0001). Similarly, the prevalence of metabolic syndrome in patients with a high WC (>102 cm) was 76%, compared to 24.5% in patients without a high WC (P<0.001). Table 5 shows the prevalence of silent CAD in our population comparing the two different high WC values and the different defining criteria for metabolic syndrome.

Table 5.

Prevalence of Silent Coronary Artery Disease Using Different Metabolic Syndrome Criteria and Waist Circumference Cutoff Points

	Prevalence of silent CAD	P
WC <94 cm vs. WC ≥94 cm	84 (18.1%) vs. 148 (24.4%)	0.012
WC ≥94 cm vs. WC >102 cm	148 (24.4%) vs. 110 (26.9%)	0.38
Metabolic syndrome NCEP-R vs. Metabolic syndrome IDF	126 (26.6%) vs. 116 (26.1%)	0.86
Metabolic syndrome IDF vs. WC ≥94 cm	116 (26.1%) vs. 148 (24.4%)	0.53
Metabolic syndrome NCEP-R vs. WC >102 cm	126 (26.6%) vs. 110 (26.9%)	0.88
Metabolic syndrome NCEP-R^a vs. metabolic syndrome NCEP-R^b	93 (30%) vs. 33 (20%)	0.026

Patients with metabolic syndrome NCEP-R with WC >102 cm as a defining risk factor component.

Patients with metabolic syndrome NCEP-R without WC >102 cm as a defining risk factor component.

CAD, coronary artery disease; WC, waist circumference; NCEP-R, revised National Cholesterol Education Program; IDF, International Diabetes Federation.

Among patients with metabolic syndrome defined by the NCEP-R, the presence of a high WC (>102 cm) as one of the defining components for metabolic syndrome was associated with a higher prevalence of silent CAD compared to patients who met metabolic syndrome criteria without a high WC (30% vs. 20%; P=0.026). Similarly, the presence of insulin resistance (fasting hyperglycemia of ≥100 mg/dL) as one of the defining components for metabolic syndrome was also associated with a higher prevalence of silent CAD compared to patients who met metabolic syndrome criteria without insulin resistance (28% vs. 16%; P=0.045). However, the presence of any of the other three components used to define metabolic syndrome, i.e., high serum triglycerides (26% vs. 28%; P=0.75), low HDL-C (28% vs. 25%; P=0.50), or an elevated blood pressure (25% vs. 33%; P=0.17), did not significantly increase the prevalence of silent CAD above their contribution to metabolic syndrome.

Similarly, among patients with metabolic syndrome defined by the IDF, the presence of insulin resistance as one of the defining components for metabolic syndrome in addition to a high WC (≥94 cm) was associated with a higher prevalence of silent CAD (29% vs. 14%, P=0.008). However, the presence of high serum triglycerides (26% vs. 26%; P=1.00), low HDL-C (26% vs. 26%; P=0.95), and an elevated blood pressure (25% vs. 30%; P=0.34) did not significantly increase the prevalence of silent CAD above the contribution of these factors to metabolic syndrome.

In our study population, the prevalence of silent CAD was not increased with a greater number of components used to define metabolic syndrome. When comparing three, four, or five defining components, the risk of silent CAD was not increased according to both the NCEP-R (23% vs. 31% vs. 31%; P=0.12) and the IDF criteria (23% vs. 30% vs. 26%; P=0.35).

Last, we also performed subgroup sensitivity analysis after excluding all patients with nonanginal chest pain. Of these 621 patients, 153 (24.6%) patients had silent CAD. On multivariable logistic regression analysis [odds ratio (OR); 95% confidence interval (CI)], a WC ≥94 cm (1.54, 1.04–2.27; P=0.028), metabolic syndrome defined by NCEP-R (1.82, 1.25–2.63; P=0.002), and metabolic syndrome defined by IDF (1.77, 1.22–2.55; P=0.002) continued to remain independent predictors of silent CAD.

Discussion

In spite of the advances in clinical medicine, the incidence of fatal cardiovascular events remains high. This may be, in part, due to the fact that physicians tend to target most treatments toward symptomatic CVD, when silent CAD continues to be the most common manifestation.^2,3 Although the exact prevalence and prognostic implications of silent CAD have not been well studied in a prospective manner, several large clinical trials have shown that the presence of silent CAD detected during baseline stress testing predicts an increased risk of future coronary events and cardiac death.^27,28 Thus, screening high-risk patients for the presence of silent CAD remains of paramount importance.

Obesity and metabolic syndrome are growing global health problems. It is estimated that only one state in the United States has a current obesity prevalence of less than 20%.⁵ In recent years, researchers have given much needed attention to obesity, specifically abdominal obesity, and have demonstrated the risk of CVD associated with it.²⁰ However, the contribution of abdominal obesity to silent CAD remains unknown. In addition to evaluating the contribution of a high WC among patients with metabolic syndrome, we believe that our study is the first to compare the different published criteria for metabolic syndrome in determining prevalence of silent CAD. In addition, given the paucity of data looking at the association of a high WC, metabolic syndrome, and silent CAD among veteran patients compared to the general population, we wish to highlight three important findings in this report.

First, our study demonstrates the importance of abdominal obesity as an independent risk factor for silent CAD. Current data show that screening for obesity in patients is not a routine practice,²⁹ thereby, missing a potentially important component of CVD risk assessment. Most prior studies looking at WC as a risk factor for CVD have used end points of cardiac infarction and related mortality to determine CAD prevalence.^{18

–21,30
–32} To determine the prevalence of silent CAD, we studied patients who underwent baseline cardiac stress testing, which offers a different viewpoint on the burden of stable CAD. Our findings contradict recently published results by Wildman et al. wherein abdominal obesity in the absence of coexistent metabolic derangements was not predictive of increased cardiovascular risk.²⁴ However, this could potentially be explained by the difference in patient population, baseline demographics, and the primary end points used in both studies.

Second, we compared the prevalence of silent CAD using two different defining criteria for metabolic syndrome, NCEP-R and IDF. The reported prevalence of metabolic syndrome in the general population is impacted by the different values used to define an elevated WC. The IDF criterion uses a lower WC as compared to the NCEP-R criterion. Therefore, more individuals meet criteria for metabolic syndrome using the IDF criterion.³³ However, in our population of male veterans, the prevalence of metabolic syndrome was not significantly different using either criterion. In the Hoorn Study³⁴ and in a recent study by Katzmarzyk et al.,²¹ it was shown that, although the presence of metabolic syndrome increased the overall cardiovascular risk, there were minimal differences in predicting the incidence of CAD and mortality across various definitions of metabolic syndrome. Our data demonstrated similar results in this regard where the prevalence of silent CAD, determined by baseline stress imaging among men with metabolic syndrome, was not statistically different using either the NCEP-R or the IDF criteria.

High WC as an index for determining the burden of visceral obesity³⁵ is a strong defining component for metabolic syndrome.^18,19,21 There is ongoing debate about whether metabolic syndrome itself confers greater overall risk for CVD in comparison to each of its individual components.^11

–15 Interestingly, in our study, there was no statistical significant difference in the prevalence of silent CAD when comparing patients with metabolic syndrome defined by NCEP-R to those with WC >102 cm, and patients with metabolic syndrome by IDF to those with WC >94 cm. Alexander et al. studied the prevalence of CAD among patients with metabolic syndrome and found that after adjusting for individual defining components such as elevated blood pressure, insulin resistance, and low HDL-C, metabolic syndrome did not predict an increased risk for CAD.³⁶ This, in the context of our results, further raises the question about whether metabolic syndrome as a “clinical syndrome” should be considered as a strong cardiovascular risk factor rather than it simply being a constellation of its individual risk factor components.

Finally, and most importantly, we report a 1.5-fold increase in the prevalence of silent CAD in patients with metabolic syndrome defined by NCEP-R, when a high WC is one of the defining components for metabolic syndrome. In addition, given that the strong association of silent CAD with diabetes mellitus and insulin resistance has already been demonstrated,^37

–41 we show a similar association where the presence of insulin resistance in patients with metabolic syndrome using either criterion is associated with an increased prevalence of silent CAD. Although hypertension, low HDL-C, and high serum triglycerides have traditionally been shown to be associated with increased prevalence of silent CAD,^31,42,43 their presence as metabolic syndrome–defining components in our patient population did not significantly increase the prevalence of silent CAD for reasons that are unclear, but potentially could be attributed to a relatively smaller sample size in our study. Age has also been strongly linked to the presence of silent CAD.^44,45 We further emphasize the risk of silent CAD with increasing age. Last, in our sample, the total number of risk factor components used to define metabolic syndrome did not significantly alter the prevalence of silent CAD.

Study limitations

Our study has recognized limitations. Subjects were only male veterans, which limits the extrapolation of these results to the general population. The population studied consisted of patients referred for stress testing due to suspected CAD. Thus, the prevalence of CAD in this group was likely higher than in the general population. Finally, information regarding the duration of exposure to each individual risk factor component comprising metabolic syndrome and previous treatment regimens was not readily available.

Conclusion

A high WC (>94 cm) is independently associated with an increased prevalence of silent CAD. This association is comparable to the association between silent CAD and metabolic syndrome as identified by both NCEP-R and IDF criteria. Besides insulin resistance, WC is the only other component of metabolic syndrome that is associated with an increased prevalence of silent CAD above the risk conferred by metabolic syndrome. This underscores the importance of abdominal obesity as a strong clinical component in the definition of metabolic syndrome in predicting the prevalence of silent CAD. We strongly believe that screening patients for abdominal obesity via measurement of WC should be used as an effective tool to identify patients who are potentially at a higher risk for silent CAD. This will allow for earlier risk assessment and preventive measures to reduce future abdominal obesity–related morbidity and mortality. In the future, further clinical studies are needed to establish screening guidelines for detection of silent CAD in an unselected patient population with abdominal obesity.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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