A lthough it is encouraging that during the past decade there has been a notable decline in the incidence of stroke in several countries around the world, 1-6 further reductions in stroke occurrence will require even better treatment of conventional risk factors, as well as the identification and treatment of nontraditional risk factors. 7 Hypertension, diabetes mellitus, hypercholesterolemia, cigarette smoking, atrial fibrillation, and carotid stenosis are definite causal risk factors because randomized controlled trials showed that treating them reduced the incidence of ischemic stroke/transient ischemic attack (TIA) or because epidemiological studies have shown that they are prospectively and independently associated with incident risk of stroke.8 Several risk models and risk calculators are available for stroke. However, they include only a few traditional risk factors, and not all ischemic strokes are explained by these factors. About 60% to 80% of all ischemic strokes can be attributed to these factors.8 Adding more factors may improve the predictive values of the risk models for stroke, and controlling nontraditional risk factors may further reduce stroke risks. The INTERSTROKE study, which examined 10 factors including less traditional factors such as obesity, psychosocial stress and depression, and ratio of apolipoprotein B to A1, found that these conditions were linked to 90% of the risk of stroke.
9The carotid substudy of Northern Manhattan studies showed that traditional risk factors explain only a minority of the variability in carotid plaque, suggesting a possible role for unaccounted nontraditional risk factors in the development of atherosclerotic plaque. 10,11 The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study confirmed the existence of a stroke belt in the southeastern United States, where the rates of stroke mortality were higher (>40%) than those of other regions.12 However, in this study, only modest differences were found in 9 known risk factors common to stroke screening (the Framingham Stroke Risk Score) between the stroke belt and the stroke buckle compared with the rest of the United States. Similarly, a stroke belt with high stroke incidence was found in north and west China.
13Of note, a high prevalence of obesity was reported in stroke belts of both United States and China (Figure). These findings indirectly suggest a role for nontraditional risk factors to predict and prevent stroke.
Search Strategy and Selection CriteriaIn this review, we defined traditional risk factors as those used in the Framingham study (ie, age, sex, hypertension, diabetes mellitus, cigarette smoking, cardiovascular disease [CVD], atrial fibrillation, and left ventricular hypertrophy) 15 and hypercholesterolemia. Others are defined as nontraditional risk factors if the association between the factors and the occurrence of stroke was demonstrated with plausible biological explanation. We identified references for this review by searching PubMed and ClinicalTrials.gov published in En...