Coronary Artery Calcification Is an Independent Stroke Predictor in the General Population

Dirk M. Hermann, MD; Janine Gronewold, MSc; Nils Lehmann, PhD; Susanne Moebus, PhD; Karl-Heinz Jckel, PhD; Marcus Bauer, MD; Raimund Erbel, MD; on behalf of the Heinz Nixdorf Recall Study Investigative Group

ALQI YUTHA

Abstract
Background and Purpose Coronary artery calcification (CAC) is a noninvasive marker of plaque load that predicts myocardial infarcts in the general population. Herein, we investigated whether CAC predicts stroke events in addition to established risk factors that are part of the Framingham risk score.

Methods A total of 4180 subjects from the population-based Heinz Nixdorf Recall study (4575 years of age; 47.1% men) without previous stroke, coronary heart disease, or myocardial infarction were evaluated for stroke events over 94.919.4 months. Cox proportional hazards regressions were used to examine CAC as stroke predictor in addition to established vascular risk factors (age, sex, systolic blood pressure, low-density lipoprotein, highdensity lipoprotein, diabetes mellitus, smoking, and atrial fibrillation).

Results Ninety-two incident strokes occurred (82 ischemic, 10 hemorrhagic). Subjects suffering a stroke had significantly higher CAC values at baseline than the remaining subjects (median, 104.8[Q1;Q3, 14.0;482.2] vs 11.2[0;106.2]; P<0.001). In a multivariable Cox regression, log 10 (CAC+1) was an independent stroke predictor (hazards ratio, 1.52 [95% confidence interval, 1.191.92]; P=0.001) in addition to age (1.35 per 5 years [1.151.59]; P<0.001), systolic blood pressure (1.25 per 10 mm Hg [1.141.37]; P<0.001), and smoking (1.75 [1.072.87]; P=0.025). CAC predicted stroke in men and women, particularly in subjects <65 years of age and independent of atrial fibrillation. CAC discriminated stroke risk specifically in participants belonging to the low (<10%) and intermediate (10%20%) Framingham risk score categories

 Vascular risk factors predict the 10-year incidence of stroke in a relatively reliable way. Unfortunately, risk factors do not offer any information about the severity of actual vascular disease With respect to cardiovascular diseases, coronary artery calcification (CAC) determined by electron beam-computed tomography (EBCT) was recently identified as potent predictor of incident myocardial infarcts

Representing a measure of global atherosclerosis, the question arose previously whether CAC also predicts incident stroke

the effect of CAC on future stroke events was previously evaluated in 3 population-based studies: the Cardiovascular Health Study (CHS),Rotterdam study,and Multi-Ethnic Study of Atherosclerosis (MESA). Notably, in none of these studies, CAC was found to represent a stroke predictor, when adjustments for classical risk factors were made

To elucidate the possible link between CAC and stroke, we herein evaluated the effect of CAC on stroke incidenHeinz Nixdorf Recall (HNR) cohort. The HNR is a population-based cohort of 4814 subjects 45 to 75 years of age that examines the role of risk factors and subclinical atherosclerosis in the development of overt vascular disease.

Method
The HNR cohort is a random sample of men and women 45 to 75 years of age, who were prospectively enrolled via mandatory citizen regis-tries in Essen, Bochum, and Mlheim/Ruhr, 3 cities of the industrialized Ruhr area, between December 2000 and August 2003 All subjects gave informed consent Exclusion criteria were inability or unwilling-ness to give informed consent, conditions (medical or other) precluding follow-up over 5 years, severe psychiatric disorders or illegal substance abuse, and pregnancy in women

Method
Computer-assisted interviews and questionnaires were used to document medical histories The study was approved by the ethical committee at the University Duisburg-Essen Of 4814 subjects included, 4356 subjects had a negative history for previous stroke, coronary heart disease, and myocardial infarcts. Of these, CAC measurements were obtained in 4180 subjects. Subjects were followed up over 94.919.4 months.

Method
Stroke events were validated by an independent internal and external end point committee that provided consensus decisions in case of disagreements CAC was defined as a focus of 4 contiguous pixels with a CT density 130 Hounsfield units. The CAC Agatston score was computed by summing weighted CAC scores of all foci in the epicardial coronary system. The CAC score was communicated neither to the participants nor to their physicians

Result
A total of 92 subjects (55 men, 37 women) developed a stroke during the follow-up period [82 ischemic, 10 hemorrhagic]. Of the ischemic strokes, 11 were macroangiopathic, 14 microangiopathic, 22 cardioembolic, and 35 unknown/other pathogenesis Subjects experienc-ing a stroke were older, had a higher body mass index, more often revealed arterial hypertension and diabetes mellitus, and had higher triglycerides and a higher FRS than subjects with-out stroke. Subjects with a stroke more frequently exhibited a clinical history of peripheral artery disease and more frequently received antihypertensive and antidiabetic medications

Result
The median age of patients experiencing a stroke event during the follow-up period was 65 years. All acquired risk factors were more prevalent in subjects >65 years rather than 65 years of age The percentage of current smokers was lower in subjects >65 years rather than 65 years of age, whereas the CAC score was higher When stratified by sex, all vascular risk factors except total and LDL cholesterol were more often noted in men than in women

Result
In line with this, stroke incidence was higher in men than in women, and men more often received antidiabetics and platelet inhibi-tors than women When stratified by CAC, the prevalence of all risk factors increased with higher CAC categories, as did stroke incidence). Antihypertensive, lipidlowering, antidiabetic, and antiplatelet drugs were more frequently documented in higher than in lower CAC categories

Discussion
Using a sample of 4180 subjects 45 to 75 years of age, we showed that CAC is an independent predictor of future stroke events in the general population. CAC predicted stroke in men and women, more potently in subjects 65 years than >65 years of age CAC discriminated stroke risk specifically in subjects belonging to the low (<10%) and intermediate (10% to 20%) FRS categories

TERIMA KASIH