title: Combining risk markers improves cardiovascular risk prediction in women.
abstract: Cardiovascular risk stratification could be improved by adding measures of atherosclerosis to current risk scores, especially in intermediate-risk individuals. We prospectively evaluated the additive value of different non-invasive risk markers (both individual and combined) for gender-specific cardiovascular risk stratification on top of traditional risk factors in a middle-aged population-based cohort. Carotid-plaques, IMT (intima-media thickness), ABI (ankle-brachial index), PWV (pulse-wave velocity), AIx (augmentation index), CAP (central augmented pressure) and CSP (central-systolic pressure) were measured in 1367 CVD (cardiovascular disease)-free participants aged 50-70 years old. Cardiovascular events were validated after a mean follow-up of 3.8 years. AUC (area-under-the-curve) and NRI (net reclassification improvement) analyses (total-NRI for all and clinical-NRI for intermediate-risk groups) were used to determine the additive value of individual and combined risk markers. Cardiovascular events occurred in 32 women and 39 men. Traditional cardiovascular risk factors explained 6.2% and 12.5% of the variance in CVD in women and men respectively. AUCs did not substantially increase by adding individual or combined non-invasive risk markers. Individual risk markers only improved reclassification in intermediate-risk women and more than in men; clinical-NRIs ranged between 48.0 and 173.1% in women and 8.9 and 20% in men. Combined non-invasive-risk markers improved reclassification in all women and even more in those at intermediate risk; 'IMT-presence-thickness-of-plaques' showed largest reclassification [total-NRI=33.8%, P=0.012; IDI (integrated-discrimination-improvement)=0.048, P=0.066; clinical-NRI=168.0%]. In men, combined non-invasive risk markers improved reclassification only in those at intermediate risk; 'PWV-AIx-CSP-CAP-IMT' showed the largest reclassification (total-NRI=14.5%, P=0.087; IDI=0.016, P=0.148; clinical-NRI=46.0%). In all women, cardiovascular risk stratification improved by adding combinations and in women at intermediate risk also by adding individual non-invasive risk markers. The additive value of individual and combined non-invasive risk markers in men is limited to men at intermediate risk only, and to a lesser extent than in women.
authors.affiliation: *Department of General Internal Medicine, Division of Vascular Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Holewijn
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Graaf
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D059289:Vascular Stiffness / Q000502:physiology