Metabolic Syndrome and Asymptomatic Peripheral Artery Disease in Subjects Over 60 Years of Age
The ankle-brachial index (ABI) is a noninvasive, low-cost, and useful test for detecting asymptomatic peripheral artery disease (PAD). An ABI <0.9 has a sensitivity of 95% and a specificity of 99% in identifying PAD when compared with arteriography (1). A low ABI predicts risk of cardiovascular death, myocardial infarction, PAD events, and stroke (2, 3). Although an elevated prevalence of a low ABI has been described in subjects with metabolic syndrome and a history of cardiovascular disease (4), there is no information of its possible association in subjects in primary prevention. The objective of the present study was to investigate the association between metabolic syndrome and the presence of asymptomatic PAD, defined by the presence of a low ABI, in subjects >60 years of age without a history of cardiovascular disease or diabetes. Also, we assessed whether the association persisted after adjustment for classical risk factors.
RESEARCH DESIGN AND METHODS
The participants of the study were subjects of both genders aged 60–79 years who accessed the Fuencarral Health Centre (Madrid) and voluntarily agreed to have an ABI measurement. Of the 1,361 subjects in whom the ABI was measured, 360 were excluded from the present study because of a diagnosis of cardiovascular disease or diabetes. The final number of participants was 1,001. Blood was taken for laboratory analyses that included fasting glucose and the lipid profile. The study was approved by the Committee on Ethics and Clinical Investigation of the Hospital Carlos III in Madrid. All of the patients gave written informed consent.
Subjects were diagnosed as having the metabolic syndrome if they met at least three of the following NCEP-ATP III (Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults) criteria (5): waist circumference >102 cm in men and >88 cm in women, triglyceride concentration ≥1.70 mmol/l (150 mg/dl), HDL cholesterol <1.03 mmol/l (<40 mg/dl) in men and <1.29 mmol/l (<50 mg/dl) in women, blood pressure ≥130/≥85 mmHg or on antihypertensive medication, and fasting glucose ≥6.1 mmol/l (>110 mg/dl). The ABI measurement procedure has been previously described (6). Participants who had an ABI <0.90 were categorized as having a low ABI.
Assessment to determine the 10-year risk for developing coronary heart disease was carried out using the Framingham risk score (5). High-risk subjects were defined as those with a 10-year risk for coronary heart disease >20%.
The statistical analyses were performed with the SPSS statistical package. Comparisons between quantitative variables were performed by unpaired Student’s t test and between qualitative variables by the χ2 test. Relationships between asymptomatic PAD and the other measured variables were evaluated using multiple logistic regression analyses with the dependent variable being the presence of an ABI <0.90.
A total of 1,001 subjects (67.1% women) participated in the study. Of them, 277 (27.6%) fulfilled the criteria of metabolic syndrome. The general characteristics of the overall study population segregated with respect to presence or absence of the metabolic syndrome are presented in Table 1.
Among the 1,001 subjects in whom ABI was measured, 20 (2%) had measurements that were unacceptable because the pulse could not be obliterated with a pressure of 250 mmHg. In 38 (3.9%) of the remaining 981 subjects, ABI was low (<0.90). The prevalence of a low ABI was significantly greater in subjects with metabolic syndrome criteria (7.3 vs. 2.5%, P < 0.001). The prevalence of a low ABI increased progressively with the increase in the number of diagnostic criteria of metabolic syndrome (P for trend <0.001).
Subjects with metabolic syndrome presented with a high cardiovascular disease risk (10-year risk score >20%) compared with the group without metabolic syndrome (18.4 vs. 5%, P < 0.001).
In the univariate analysis, age, tobacco consumption, LDL cholesterol, HDL cholesterol, triglyceride concentrations, hypertension, and metabolic syndrome (OR 3.0 [95% CI 1.57–5.81]; P = 0.0009) were all significantly associated with a low ABI. In multivariate analysis, when those variables that were significantly related to a low ABI in the univariate analysis were introduced as independent variables, the association of metabolic syndrome with low ABI lost its statistical significance (P = 0.421). Nevertheless, the significant associations with age, tobacco, LDL cholesterol, triglycerides, and hypertension persisted.
This is the first study to describe the association between metabolic syndrome and asymptomatic PAD in subjects without a clinical history of cardiovascular disease or diabetes.
In our study, the presence of metabolic syndrome was associated with a higher percentage of subjects considered to be at high risk. Several studies have described a high risk of cardiovascular disease events and mortality associated with metabolic syndrome (7–9). However, in some studies (10–13) this association disappears when adjusted for the components of metabolic syndrome or for classical risk factors. Nevertheless, other authors (7–9,13) have observed a significant association between metabolic syndrome and cardiovascular disease, even following adjustment for classical risk factors, suggesting that the increase in risk associated with metabolic syndrome was not entirely explicable by the classical factors.
Only one previous study (4) investigated the prevalence of a low ABI in subjects with metabolic syndrome and a history of cardiovascular disease; 14% had a low ABI compared with 10% of those who did not have metabolic syndrome.
Classical risk factors are frequently associated with a low ABI (13–15). As such, given that the principal components of metabolic syndrome are associated with a low ABI, the strong associations that we observed in the univariate analysis are not surprising—a low ABI being three times more frequently observed when metabolic syndrome criteria are fulfilled. But, as has been described with the association between metabolic syndrome and cardiovascular disease, this association disappears with adjustment for other risk factors. As such, the diagnosis of metabolic syndrome does not extend the patient’s classical risk factor status when assessing the risk of suffering asymptomatic PAD.
We conclude that in subjects 60–79 years of age without cardiovascular disease or diabetes, while metabolic syndrome is significantly associated with the presence of asymptomatic PAD, it does not add much to the classical risk factors in the prediction of asymptomatic PAD.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
- Received October 10, 2005.
- Accepted October 11, 2005.
- DIABETES CARE