by
Nicolas Rodondi;
Isabella Locatelli;
Drahomir Aujesky;
Javed Butler;
Eric Vittinghoff;
Eleanor Simonsick;
Suzanne Satterfield;
Anne B. Newman;
Peter Wilson;
Mark J. Pletcher;
Douglas C. Bauer
Background: Guidelines for the prevention of coronary heart disease (CHD) recommend use of Framingham-based risk scores that were developed in white middle-aged populations. It remains unclear whether and how CHD risk prediction might be improved among older adults. We aimed to compare the prognostic performance of the Framingham risk score (FRS), directly and after recalibration, with refit functions derived from the present cohort, as well as to assess the utility of adding other routinely available risk parameters to FRS. Methods: Among 2193 black and white older adults (mean age, 73.5 years) without pre-existing cardiovascular disease from the Health ABC cohort, we examined adjudicated CHD events, defined as incident myocardial infarction, CHD death, and hospitalization for angina or coronary revascularization. Results: During 8-year follow-up, 351 participants experienced CHD events. The FRS poorly discriminated between persons who experienced CHD events vs. not (C-index: 0.577 in women; 0.583 in men) and underestimated absolute risk prediction by 51% in women and 8% in men. Recalibration of the FRS improved absolute risk prediction, particulary for women. For both genders, refitting these functions substantially improved absolute risk prediction, with similar discrimination to the FRS. Results did not differ between whites and blacks. The addition of lifestyle variables, waist circumference and creatinine did not improve risk prediction beyond risk factors of the FRS. Conclusions: The FRS underestimates CHD risk in older adults, particularly in women, although traditional risk factors remain the best predictors of CHD. Re-estimated risk functions using these factors improve accurate estimation of absolute risk.
BACKGROUND—: Free radical scavengers have failed to improve patient outcomes promoting the concept that clinically important oxidative stress (OS) may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of non-free radical mediated oxidative stress with clinical outcomes.
METHODS AND RESULTS—: Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7±2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (p<0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (=+1 SD & <-1 SD respectively) were associated with higher mortality (adjusted HR 1.63 (95% CI 1.19-2.21; HR 2.19 (95% CI 1.50-3.19), respectively) compared to those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR 1.92 (95% CI 1.39-2.64) and was independent of and additive to hs-CRP level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction.
CONCLUSIONS—: A high burden of OS, quantified by the plasma aminothiols, cystine, glutathione and their ratio is associated with mortality in patients with CAD, a finding that is independent of and additive to the inflammatory burden. Importantly, this data supports the emerging role of non-free radical biology in driving clinically important oxidative stress.
Introduction: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown.
Methods and Results: We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox's proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C‐reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P<0.0001) and its severity (P<0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden's index) predicted future risk of MI (hazard ratio [HR]=3.2; P<0.0001), cardiac death (HR=2.62; P<0.0001), and the combined endpoint of death and MI (HR=1.9; P<0.0001), even after adjustment of covariates. The C‐statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR.
Conclusion: Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD.
Background: High epicardial adipose tissue (EAT) attenuation (Hounsfield units [HUs]) on computed tomography is considered a marker of inflammation and is associated with an increased risk of cardiovascular events. Statins reduce the volume of EAT, but it is unknown whether they affect EAT HUs. Methods and Results: We reviewed the chest computed tomographic scans of 420 postmenopausal women randomized to either 80 mg of atorvastatin or 40 mg of pravastatin daily and rescanned after 1 year to measure change in coronary artery calcium score. EAT HUs were measured near the proximal right coronary artery and remote from any area of coronary artery calcium. Computed tomographic images were also queried for subcutaneous adipose tissue (SubQ) attenuation (HUs) change over time. The mean patients’ age was 65±6 years. The baseline EAT HU value was higher than the SubQ HU value (−89.4±24.0 HU versus −123.3±30.4 HU; P<0.001). The EAT HU value decreased significantly in the entire cohort (−5.4±29.7 HU [−6% change]; P<0.001), but equally in the patients given atorvastatin and pravastatin (−6.35+31 HU and −4.55+28 HU; P=0.55). EAT HU change was not associated with change in total cholesterol, low-density lipoprotein cholesterol, coronary artery calcium, and EAT volume (all P=not significant). Change in high-density lipoprotein cholesterol was marginally associated with EAT HU change (P=0.07). Statin treatment did not induce a change in SubQ HUs. Conclusions: Statins induced a decrease in EAT HUs over time, independent of intensity of low-density lipoprotein cholesterol lowering. The positive effect on EAT and the neutral effect on SubQ suggest that statins induced a decrease in metabolic activity in EAT by reduction in cellularity, vascularity, or inflammation. The clinical significance of the observed change in EAT HUs remains to be demonstrated.