Robert R. Pearson

Effect of fasting glucose levels on mortality rate in patients with and without diabetes mellitus and coronary artery disease undergoing percutaneous coronary intervention

BACKGROUND Diabetes mellitus (DM) is predictive of increased mortality for patients with coronary artery disease (CAD). To what extent this risk extends below the diabetic threshold (fasting glucose level [FG] <126 mg/dL) is uncertain. METHODS The study objective was to determine the risk associated with FG in a prospectively assembled cohort of 1612 patients with CAD who were undergoing percutaneous coronary intervention (PCI) and had a FG measured or a clinical diagnosis of DM (CDM). Patients were grouped as: CDM; no CDM, but FG > or =126 mg/dL (ADA-DM); impaired FG, 110-125 mg/dL (IFG); or normal FG, <110 mg/dL (NFG). Survival was assessed for 2.8 +/- 1.2 years. RESULTS The average patient age was 62 +/- 12 years; 74% of the patients were men. Diagnostic frequencies were: CDM, 24%; ADA-DM, 18%; IFG, 19%; and NFG, 39%. Mortality rates were greater for patients in the CDM (44/394 [11.2%], P <.0001), ADA-DM (27/283 [9.5%], P <.001), and IFG (20/305 [6.6%], P =.04) groups than patients in the NFG group(12/630 [1.9%]). Independent receiver operating characteristic analysis chose FG > or =109 mg/dL as the best cutoff for increased risk (sensitivity, 81%; specificity, 51%). After adjustment with Cox regression analysis, CDM (hazard ratio [HR] = 5.0; 95% CI, 2.6-9.6; P <.001), ADA-DM (HR, 4.1; 95% CI, 2.1-8.2; P <.001), and IFG status (HR, 3.2; 95% CI, 1.5-6.5; P =.002) remained independent predictors of mortality. CONCLUSIONS Prognostically significant abnormalities of FG are much more prevalent (61%) than expected in patients with CAD who are undergoing PCI. Despite revascularization, the associated mortality risk of even mild elevations in FG is substantial, emphasizing the importance of early detection and treatment of glycemia-related risk.

Statin therapy is associated with reduced mortality across all age groups of individuals with significant coronary disease, including very elderly patients.

OBJECTIVES This study evaluated the effect of statin therapy on mortality in individuals with significant coronary artery disease (CAD) stratified by age. BACKGROUND Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) significantly reduce morbidity and mortality in individuals with CAD. Unfortunately, the large statin trials excluded individuals over 80 years old, and it is therefore unknown whether very elderly individuals benefit from statins as do younger individuals. METHODS A cohort of 7,220 individuals with angiographically defined significant CAD (> or =70%) was included. Statin prescription was determined at hospital discharge. Patients were followed up for 3.3 +/- 1.8 years (maximum 6.8). Patients were grouped by age (<65, 65 to 79, and > or =80 years) to determine whether statin therapy reduced mortality in an age-dependent manner. RESULTS Average age was 65 +/- 12 years; 74% were male; and 31% had a postmyocardial infarction status. Overall mortality was 16%. Elderly patients were significantly less likely to receive statins than younger patients (> or =80 years: 19.8%; 65 to 79 years: 21.1%; <65 years: 28.0%; p < 0.001). Mortality was decreased among statin recipients in all age groups: > or =80 years: 29.5% among patients not taking a statin versus 8.5% of those taking a statin (adjusted hazard ratio [HR] 0.50, p = 0.036); 65 to 79 years: 18.7% vs. 6.0% (HR 0.56, p < 0.001); and <65 years: 8.9% vs. 3.1% (HR 0.70, p = 0.097). CONCLUSIONS Statin therapy is associated with reduced mortality in all age groups of individuals with significant CAD, including very elderly individuals. Although older patients were less likely to receive statin therapy, they received a greater absolute risk reduction than younger individuals. More aggressive statin use after CAD diagnosis may be indicated, even in older patients.

Serum Uric Acid Independently Predicts Mortality in Patients with Significant, Angiographically Defined Coronary Disease

Background: Uric acid is a nontraditional risk factor implicated in the development of coronary artery disease (CAD). This study prospectively evaluated the predictive value of serum uric acid (SUA) levels for mortality after angiographic diagnosis of CAD. Methods: Blood samples were collected from 1,595 consecutive, consenting patients with significant, angiographically defined CAD (stenosis 70%). Baseline and procedural variables were recorded and levels of SUA were measured. Patients were followed to death or to the time of contact (mean 2.6 years, range 1.8–5.0 years). Results: Patients averaged 65 ± 11 years of age, 78% were male and 170 subjects died during the follow-up period. In univariate analysis of prospectively defined quintiles, SUA predicted all-cause mortality (fifth quintile vs. first four quintiles: hazard ratio 1.9, p < 0.001). In multivariable Cox regression controlling for 20 covariables, independent predictive value for mortality was retained by SUA (hazard ratio 1.5, confidence interval 1.02–2.1, p = 0.04). In subgroup analysis based on diuretic use status, SUA independently predicted mortality among patients not using diuretics, while SUA was not a significant predictor of mortality among those who used diuretics. Conclusions: In patients with significant, angiographically defined CAD, SUA predicted mortality independent of traditional risk factors. This suggests that elevated SUA may be a risk factor for mortality in patients with significant cardiovascular disease and may be a stronger secondary than primary risk factor in CAD.

Surgical Revascularization Is Associated With Improved Long-Term Outcomes Compared With Percutaneous Stenting in Most Subgroups of Patients With Multivessel Coronary Artery Disease Results From the Intermountain Heart Registry

Background— Coronary artery bypass surgery (CABG) and percutaneous coronary intervention with stenting (PCI-S) are both safe and effective approaches for revascularization in patients with multivessel coronary artery disease. However, conflicting information exists when comparing the efficacy of the two methods. In this study, we examined the outcomes of major adverse cardiovascular events and death for subgroups of typical “real-world” patients undergoing coronary revascularization in the modern era. Methods and Results— Patients were included if they were revascularized by CABG or PCI-S, had ≥5 years of follow-up, and had ≥2-vessel disease. Patients were followed for an average of 7.0±3.2 years for incidence of death and major adverse cardiovascular events (death, myocardial infarction, or repeat revascularization). Multivariate regression models were used to correct for standard cardiac risk factors including age, sex, hyperlipidemia, diabetes mellitus, family history of coronary artery disease, smoking, hypertension, heart failure, and renal failure. Subgroup analyses were also performed, stratified by age, sex, diabetes, ejection fraction, and history of PCI-S, CABG, or myocardial infarction. A total of 6369 patients (CABG 4581; PCI-S 1788) were included. Age averaged 66±10.9 years, 76% were male, and 26% were diabetic. Multivariate risk favored CABG over PCI-S for both death (hazard ratio 0.85; P=0.001) and major adverse cardiovascular events (hazard ratio 0.51; P<0.0001). A similar advantage with CABG was also found in most substrata, including diabetes. Conclusions— In this large observational study of patients undergoing revascularization for multivessel coronary artery disease, a long-term benefit was found, in relationship to both death and major adverse cardiovascular events, for CABG over PCI-S regardless of diabetic status or other stratifications.

Soluble CD40 Ligand as a Predictor of Coronary Artery Disease and Long-Term Clinical Outcomes in Stable Patients Undergoing Coronary Angiography

Background: In patients with acute coronary syndrome (ACS), elevated levels of soluble CD40 ligand (sCD40L) are associated with increased risk of cardiovascular events. We evaluated sCD40L levels and future cardiovascular events in patients not experiencing ACS. Methods: Serum sCD40L levels were measured in 909 patients undergoing angiography. A three-way matching scheme (age, gender and catheterization time period) identified 303 patients with coronary artery disease (CAD) who experienced a cardiac event within 1 year (CAD/event), 303 patients with CAD free of events (CAD/no event) and 303 patients without CAD and free of events (no CAD). Results: Average age was 64 ± 11 years; 74% were males. Median (± SE) sCD40L levels were higher for no CAD patients (335 ± 60 pg/ml) compared to CAD (248 ± 65 pg/ml, p = 0.01) and to CAD/event (233 ± 63 pg/ml, p < 0.001). There was no significant difference in median sCD40L levels between CAD/no event and CAD/event patients. Higher sCD40L quartiles were associated with a significant decrease in the risk of CAD/event versus no CAD (quartile 4 versus quartile 1: odds ratio = 0.59, p = 0.03). There was a nonsignificant trend towards a decreased risk of CAD as compared to no CAD, and for CAD/event versus CAD. Conclusions: In non-ACS patients, higher sCD40L levels were associated with a decreased risk of CAD. This novel interaction of sCD40L raises interesting questions for CAD pathogenesis.

Risk of nephropathy is not increased by the administration of larger volume of contrast during coronary angiography.

It is proposed that contrast-induced nephropathy (CN) correlates with the use of increasing contrast volumes during coronary angiography. This supposition has led to the current recommendation to limit the dose of contrast in patients at high risk for renal dysfunction. Limits in contrast dosing may negatively impact the evaluation of patients undergoing cardiac catheterization for myocardial infarction and acute coronary syndrome. The objective of this study was to empirically assess, in a large population, the presence and strength of this correlation. Baseline blood samples and clinical information were obtained from 5256 consenting patients hospitalized for coronary angiography. Levels of serum creatinine were measured pre- and postcatheterization, and the total change in serum creatinine was calculated. Nephropathy was defined as a change of > or =0.5 mg/dL. The total volume of contrast dye (iopamidol, nonionic) used during the angiography procedure was recorded. Logistic regression was used for the primary analysis.The average age was 64 +/- 14 years, and 67% of patients were male. Paradoxically, the incidence of CN was inversely related to the volume in the overall population: 16%, 14%, 8%, and 7% for quartile (Q) 1 (<115 mL), Q2 (115-160 mL), Q3 (161-225 mL), and Q4 (>225 mL) of contrast, respectively (P-trend <0.001). In multivariable regression, this trend toward lower CN remained (Q1 (referent) OR = 1.0, Q2: 1.02, Q3: 0.60, Q4: 0.53, P < 0.001). Other predictors included age, left ventricular ejection fraction, diabetes, and baseline creatinine level (all P < 0.001). For patients at high risk, with a baseline creatinine >2.0 mg/dL (n = 415), contrast volume (Q1: <75 mL, Q2: 75-120 mL, Q3: 121-170 mL, Q4: >170 mL) did not predict either increased or decreased risk of CN (48%, 42%, 49%, 43%, respectively, P-trend = 0.76). This lack of predictive value remained after multivariable adjustment.In this large population, no association was found between the amount of contrast used during angiography and the incidence of CN in patients at initial high risk. The apparent inverse relation of risk with volume in the overall population is likely explained by clinical practice bias. If confirmed, these results may have important clinical implications.