Although coronary heart disease (CHD) and peripheral arterial disease (PAD) share a handful of characteristics and risk factors, they affect different vascular territories and vary in pathogenesis, a study of more than two decades has found.

Lead researcher Hugh Tunstall-Pedoe, MD, and co-authors of the study explained in their paper that while CHD and stroke are widely studied and their predictors have been exhaustively researched for years, less common illnesses like PAD have been neglected, leaving medical experts with little information about the etiology of the disease. The authors, who called PAD a “cardiovascular iceberg” due to its lack of visibility in the field, noted PAD is clinically more rare than CHD and stroke, “the lion and tiger of CVD.” PAD also often presents itself later in a patient’s life, but it’s still a global killer and is increasing in importance worldwide.

Tunstall-Pedoe and his team recruited 15,373 healthy men and women across Scotland between the years 1984 and 1995, and followed those individuals for two decades in an attempt to document predictors of future heart disease. None of the patients, all between 30 and 75 years old at baseline, had experienced cardiovascular disease before enrollment in the trial, known as the Scottish Heart Health Extended Cohort (SHHEC) study.

Researchers used baseline findings, initial statistics and test information from stored serum samples to calculate 45 risk factors in the men and women studied. Initial variables included age, sex, family history of CHD, socioeconomic status, diabetes, smoking status, systolic blood pressure and cholesterol measurements, according to the researcb. After 20 years of follow-up, nearly 20 percent of participants—3,098 individuals—developed CHD, while 3.2 percent, or 499 people, were documented as having developing PAD.

More than half of the cohort who developed PAD also developed CHD, with CHD presenting itself first in 143 patients and PAD coming first in 97. In 45 cases, the diseases developed simultaneously.

Tunstall-Pedoe and colleagues found the most prominent predictor of PAD was smoking, followed closely by diabetes mellitus and inflammation. In CHD patients, they wrote, the “blame (was) more evenly distributed,” generally attributed to variables like high cholesterol. Family history of heart disease and socioeconomic status proved to be important predictors of disease in both cases.

While these results were able to place new or neglected biomarkers in context and provide insight into the pathogenesis of PAD in particular, the study’s authors wrote that doesn’t necessarily make the information widely relevant.

“The results of this study are of interest in causation but do not necessarily mean that separate risk factor scores for different cardiovascular endpoints would be useful,” they wrote. “Clinically diagnosed PAD is delayed, less frequent and often follows the onset of CHD, so its independent prediction is of lesser clinical interest than cardiovascular disease as a whole.”