Background The prognostic importance of hemoglobin is controversial. We investigated the prognostic importance of baseline and in-treatment hemoglobin in the LIFE study. Methods Eight thousand one ...hundred ninety-four LIFE patients with hypertension and left ventricular hypertrophy with available baseline hemoglobin measurements were randomized to losartan- or atenolol-based treatment and followed for 4.8 years for end points of all-cause mortality and composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Results U-shaped relations were observed between deciles of baseline hemoglobin and all-cause mortality and the composite end point. In univariate Cox models, baseline hemoglobin in the lowest gender-specific decile (women/men: <12.5/13.4 g/dL) was associated with all-cause mortality (hazard ratio HR 2.01, 95% CI 1.64-2.64) and the composite end point (HR 1.53, 95% CI 1.27-1.85, both P < .001), whereas hemoglobin in the highest gender-specific decile (women/men: ≥15.0/16.2 g/dL) was not. The decrease in hemoglobin was higher ( P < .001) in patients allocated to losartan- (14.3-13.8 g/dL) versus atenolol-based treatment (14.3-14.0 g/dL). In Cox models with the same gender-specific definitions for high and low hemoglobin as time-varying covariates with adjustment for treatment allocation and established risk factors and diseases, hemoglobin in the lowest decile was associated with higher rates of all-cause mortality (HR 3.03, 95% CI 1.89-4.85, P < .001) and the composite end point (HR 1.36, 95% CI 1.08-1.71, P < .01), whereas hemoglobin in the highest decile was not. Conclusions After adjusting for other risk factors, relatively low, but not high, hemoglobin during antihypertensive treatment was associated with higher incidence of all-cause mortality and the composite end point.
Objectives The goal of this study was to compare the performance of several measures of carotid intima-media thickness (C-IMT) as predictors of cardiovascular events (CVEs), and to investigate ...whether they add to the predictive accuracy of Framingham risk factors (FRFs). Background Various markers of subclinical atherosclerosis have been identified as predictors of CVEs, but the most powerful variable is still under debate. Methods A cohort study was carried out in 5 European countries. A total of 3,703 subjects (median age 64.4 years; 48% men) were followed-up for a median of 36.2 months, and 215 suffered a first CVE (incidence: 19.9/1,000 person-years). Results All measures of C-IMT and the interadventitia common carotid artery diameter (ICCAD) were associated with the risk of CVEs, after adjustment for FRFs and therapies (all p < 0.005). The average of 8 maximal IMT measurements (IMTmean-max ), alone or combined with ICCAD, classified events and non-events better than the common carotid mean IMT (net reclassification improvement NRI: +11.6% and +19.9%, respectively; both p < 0.01). Compared with classification based on FRFs alone, the NRI resulting from the combination of FRFs+ICCAD+IMTmean-max was +12.1% (p < 0.01). The presence of at least 1 plaque (maximum IMT >1.5 mm) performed significantly worse than composite IMTs that incorporated plaques (p < 0.001). Adjusted Kaplan-Meier curves showed that individuals with a FRS = 22.6% (cohort average), and both IMTmean-max and ICCAD above the median, had a 6.5% risk to develop a CVE over 3 years versus a 3.4% risk for those with the same FRS, and both IMTmean-max and ICCAD below the median. Conclusions A risk stratification strategy based on C-IMT and ICCAD as an adjunct to FRFs is a rational approach to prevention of cardiovascular disease.