Coronary artery disease and elevated serum fibrinogen were stronger predictors of peripheral vascular disease in subjects younger than 60 years than in older subjects, according to a study based on data from the National Health and Nutrition Examination Survey 1999–2002.
Chronic renal insufficiency was more highly predictive of peripheral vascular disease (PVD) in subjects aged 60 years and over, according to Dr. Louis M. Messina and colleagues at the University of California, San Francisco. Their analysis was presented at the annual meeting of the Western Vascular Society, Deer Valley, Utah.
The researchers used the NHANES data to determine the prevalence of premature PVD in the U.S. population, and used presumptive risk factors as covariates to model the occurrence of PVD.
Premature PVD—occurring in patients under age 60 years—is associated with an extremely poor prognosis, including high rates of cardiovascular morbidity, limb loss, and premature death. Previous studies have been small, have dealt with a limited number of risk factors, and focused on coronary vascular disease as the outcome of interest, according to the researchers.
Based on the hypothesis that there was an interaction between risk factors and age, the investigators analyzed the data to compare the population aged less than 60 years (mean age approximately 49) with those 60 years and older (mean age approximately 70).
NHANES began to provide data in 1999 from detailed lower extremity examinations, including measurement of the ankle-brachial index (ABI). An ABI of less than 0.9 was considered indicative of lower peripheral vascular disease, according to the researchers, and was correlated with the other variables collected in the sampled population. Previous research has shown that a low ABI is one of the strongest predictors of cardiovascular morbidity and all-cause mortality.
The investigators compared data from 2,498 patients under age 60 with those from 2,585 patients aged 60 years and older. Peripheral vascular disease rates were approximately 2% in the younger group and 12% in the older group, a highly significant difference.
A history of coronary artery disease appeared to be highly predictive of PVD in persons who were under age 60 (premature PVD). The odds ratio was 2.9 for this younger group, compared with about 1.3 for the older population.
“It is not surprising that atherosclerotic disease in the peripheral vascular bed is found concomitantly with disease in the coronary vascular bed,” the researchers wrote. “However, the strength of the interaction between younger and older patients deserves emphasis. PVD in the younger age group is much more strongly associated with other cardiovascular conditions than in the older population.”
In an analysis of the other possible risk factors, they found that a 10-mg/dL increase in fibrinogen was associated with a 7% increase in odds in subjects under age 60, compared with a 3% increase in patients 60 years and older.
Although the authors did not believe this result was sufficient to indicate wide-scale screening of high fibrinogen levels to detect PVD, they did suggest that it may have clinical relevance for secondary intervention, since fibrates and niacin can lower fibrinogen levels.
In contrast, a decreased creatinine clearance was significantly associated with PVD in individuals aged 60 and older, with a 10-unit decrease in clearance affording a 16% increase in the odds ratio for PVD. There was no significant correlation in the younger age group, according to the researchers.
Strong risk factors that are independently associated with PVD regardless of age category include smoking and hypertension. Metaanalysis of plasma homocysteine levels showed only a weak association with the development of PVD.
Although there was no difference found in risk associated with gender between the age groups, being male was a significant overall predictor (odds ratio slightly greater than 2.0).
“This study is the first paper to address the question as to what risk factors for atherosclerosis might distinguish premature-onset atherosclerosis from that seen in the 60− and 70-year age groups,” Dr. Messina said in an interview.
“That premature peripheral vascular disease is associated with elevated fibrinogen suggests what many had suspected but not proven, that premature PVD is associated with a 'hypercoagulable state.' The other important risk factor was the presence of coronary artery disease. That coronary artery disease correlated more closely with premature peripheral vascular disease in those less than 60 years of age is equally surprising,” he added.
NHANES information and its data sets are at www.cdc.gov/nchs/nhanes.htm