Heather Conradson

Microvascular Function Predicts Cardiovascular Events in Primary Prevention Long-Term Results From the Firefighters and Their Endothelium (FATE) Study

Background— Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of endothelial function and other vascular markers in apparently healthy men. Methods and Results— The cohort consisted of 1574 men (age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation and its microvascular stimulus, hyperemic velocity, carotid intima-media thickness, and C-reactive protein. Cox proportional hazard models evaluated the relationship between vascular markers, Framingham risk score, and time to a first composite cardiovascular end point of vascular death, revascularization, myocardial infarction, angina, and stroke. Subjects had low median Framingham risk score (7.9%). Cardiovascular events occurred in 71 subjects (111 events) over a mean follow-up of 7.2±1.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92; P=0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90; P=0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83; P=0.002) but not C-reactive protein (P=0.35) were related to events in a multivariable analysis that included Framingham risk score (per unit SD). Furthermore, the addition of hyperemic velocity to Framingham risk score resulted in a net clinical reclassification improvement of 28.7% (P<0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% (P=0.24). Conclusions— In men, hyperemic velocity, the stimulus for flow-mediated dilation, but not flow-mediated dilation itself was a significant risk marker for adverse cardiovascular outcomes. The prognostic value was additive to traditional risk factors and carotid intima-media thickness. Hyperemic velocity, a newly described marker of microvascular function, is a novel tool that may improve risk stratification of lower-risk healthy men.

Automated oscillometric blood pressure versus auscultatory blood pressure as a predictor of carotid intima-medial thickness in male firefighters.

Automated oscillometric blood pressure versus auscultatory blood pressure as a predictor of carotid intima–medial thickness in male firefighters

The effect of iron status on vascular health

The effect of increased iron stores on the progression of atherosclerosis and endothelial health remains inconclusive. This study was designed to evaluate the relationship between hemochromatosis genotypes, serum ferritin levels and presymptomatic vascular abnormalities in a cohort of healthy subjects. Carotid intima-media thickness (CIMT) and brachial flow-mediated vasodilation (FMD) were assessed by high-resolution ultrasound in 907 male (47 ± 10 years) participants enrolled in the Firefighters and their Endothelium (FATE) study. Analyses of the hemochromatosis C282Y, H63D and S65C alleles were simultaneously determined by a single nucleotide polymorphism (SNP) primer extension method. It was found that brachial FMD was not related to serum ferritin or hemochromatosis genotype status. The presence of a hemochromatosis-associated genotype (n = 18) or heterozygosity for the C282Y genotype (n = 98) was not associated with an increased mean CIMT. After adjustment for conventional risk factors, serum ferritin was also not associated with mean CIMT. In conclusion, neither ferritin nor a hemochromatosis genotype was related to brachial endothelial function or carotid atherosclerosis. The present study does not support the hypothesis that mild to moderately increased iron stores are associated with enhanced atherosclerosis risk.

Effect of angiotensin-converting enzyme inhibition on C-reactive protein levels: The Ramipril C-Reactive pRotein Randomized evaluation (4R) trial results

BACKGROUND Plasma levels of the inflammatory biomarker C-reactive protein (CRP) predict cardiovascular risk and may represent a target for treating and/or monitoring risk-reduction strategies. The effect of angiotensin-converting enzyme inhibitors on CRP levels has not been adequately studied. METHODS A total of 264 men and women, with CRP levels of 2 mg/L or greater and no history of cardiovascular disease, were enrolled in a 12-week randomized, double-blind, placebo-controlled study. Participants were randomly assigned to receive 10 mg/day of ramipril (n=132) or placebo (n=132) for 12 weeks. The main outcome measure was the change in CRP levels from baseline to 12 weeks in the ramipril- versus placebo treated patients. RESULTS The mean (+/- SD) age was 53+/-9 years (60% men). Baseline demographics were similar between the volunteers allocated to receive either placebo or ramipril. The geometric mean CRP at baseline was 3.84 mg/L (95% CI 3.62 mg/L to 4.06 mg/L). The percentage change in geometric mean CRP values over 12 weeks was --13.2% (95% CI --22.3% to --3.2% ) in the placebo group compared with --21.1% (95% CI --29.9% to --11.2%) in the ramipril group (P nonsignificant), indicating no significant reduction in the primary end point of the trial. CONCLUSIONS A 12-week ramipril treatment protocol for healthy middle-aged volunteers did not lower CRP levels compared with placebo. However, because of the inherent variability of CRP levels, a much larger study is required to exclude a small treatment effect.