The INTERSTROKE Study: hypertension is by far the most important modifiable risk factor for stroke

Abstract

The Global Burden of Disease Study 2015 [1] reported that the five largest contributors to global disabilityadjusted life-years (DALYs) among diseases, injuries and risk factors were high systolic blood pressure (212 million), smoking (149 million), high fasting plasma glucose (143 million), high body mass index (120 million million) and childhood undernutrition (113 million). We [2] believe that the Global Burden of Disease Study is both the most useful global effort to inform governments, health care providers and the population at large of the real issues of risk factors, diseases and injuries in the world and the most important global study to reveal that hypertension has remained the leading risk factor for disease and death worldwide for the past quarter century. Similarly, the INTERSTROKE investigators recently quantified the importance of modifiable risk factors for acute stroke in different regions of the world, in key populations, and in major stroke subtypes [3]. From early 2007 and through mid-2015, as many as 10,388 patients with ischemic stroke and 3059 patients with intracerebral haemorrhage were compared with 13,472 control persons in 32 countries. Ten potentially modifiable risk factors were collectively associated with approximately 90% of the population attributable risks of stroke in each major region of the world. These associations were consistent in different ethnic groups, both genders and all age groups. Estimations of population attributable risks of stroke were based on logistic models; using this method [4] addition of population attributable risks for individual risk factors usually exceeds 100% although the overall attributable risk for the composite of these risk factors is less than 100%. Previous history of hypertension or blood pressure of 140/90mm Hg or higher (Odds ratio 2.98, 99% CI 2.72–3.28, attributable risk 47.9%, 99% CI 45.1–50.6) was by far the most important of the modifiable risk factors. Other population attributable modifiable risk factors, in descending order of importance, included physical activity (35.8%), apolipoprotein B/A1 ratio (26.8%), diet (23.2%), waist-to-hip ratio (18.6%), psychosocial factors (17.4%), current smoking (12.4%), cardiac causes (9.1%), alcohol consumption (5.8%), and diabetes mellitus (3.9%). The INTERSTROKE investigators found evidence of regional and ethnic variations in magnitude of importance of individual risk factors, though the collective contribution of these ten risk factors to stroke risk was consistent in all populations, suggesting that general approaches to prevention of stroke can be similar worldwide. Since 70–80% of strokes can be prevented by reducing blood pressure with antihypertensive drug treatment, e.g. 30/15mm Hg [5], as an example reduction from average baseline blood pressure of 174/98 to achieved average 144/81mmHg in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study [6], the INTERSTROKE investigators have reminded us once again about the need for careful assessment and treatment of hypertension. We are not sure of the optimal blood pressure treatment target, but we are sure that treatment of hypertension is effective in preventing stroke, and there seems to be no J-curve at low target levels, as in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial [7,8]. It is our opinion then that a target blood pressure of 130/80mm Hg or lower is beneficial, particularly in people at high risk of stroke.