Background Coronary heart disease and peripheral arterial disease (PAD) affect different vascular territories. Supplementing baseline findings with assays from stored serum, we compared their 20‐year predictors.
Methods and Results We randomly recruited 15 737 disease‐free men and women aged 30 to 75 years across Scotland between 1984 and 1995 and followed them through 2009 for death and hospital diagnoses. Of these, 3098 developed coronary heart disease (19.7%), and 499 PAD (3.2%). Hazard ratios for 45 variables in the Cox model were adjusted for age and sex and for factors in the 2007 ASSIGN cardiovascular risk score. Forty‐four of them were entered into parsimonious predictive models, tested by c‐statistics and net reclassification improvements. Many hazard ratios diminished with adjustment and parsimonious modeling, leaving significant survivors. The hazard ratios were mostly higher in PAD. New parsimonious models increased the c‐statistic and net reclassification improvements over ASSIGN variables alone but varied in their components and ranking. Coronary heart disease and PAD shared 7 of the 9 factors from ASSIGN: age, sex, family history, socioeconomic status, diabetes mellitus, tobacco smoking, and systolic blood pressure (but neither total nor high‐density lipoprotein cholesterol); plus 4 new ones: NT‐pro‐BNP, cotinine, high‐sensitivity C‐reactive protein, and cystatin‐C. The highest ranked hazard ratios for continuous factors in coronary heart disease were those for age, total cholesterol, high‐sensitivity troponin, NT‐pro‐BNP, cotinine, apolipoprotein A, and waist circumference (plus 10 more); in PAD they were age, high‐sensitivity C‐reactive protein, systolic blood pressure, expired carbon monoxide, cotinine, socioeconomic status, and lipoprotein (a) (plus 5 more).
Conclusions The mixture of shared with disparate determinants for arterial disease in the heart and the legs implies nonidentical pathogenesis: cholesterol dominant in the former, and inflammation (high‐sensitivity C‐reactive protein, diabetes mellitus, smoking) in the latter.
What Is New?
- Large prospective studies, with limited risk‐factor measurements, may conclude that risk factors for peripheral arterial disease (PAD) and coronary heart disease are the same.
- The Scottish Heart Health Extended Cohort (SHHEC) study involved measurement of 45 factors with follow‐up of 15 737 men and women over 20 years, generating 3098 cases of coronary heart disease and 499 cases of PAD, enabling detailed comparison of predictors.
What Are the Clinical Implications?
- Despite overlap, predictors differed for PAD and coronary heart disease. Total cholesterol, dominant in coronary heart disease, was not predictive in PAD, where inflammatory markers dominated.
- Diabetes mellitus was a powerful predictor of PAD but not the most common cause.
- Tobacco smoking was the predominant cause of PAD, evidenced both by self‐report and several biochemical measures of smoking, which reinforced prediction.
- A 3.2% incidence of clinical cases, over 20 years, does not warrant a separate PAD predictive score in healthy subjects, compared with predicting cardiovascular disease as a whole.
- Differing predictors suggest mechanisms for future interventions.
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