Adiponectin, free fatty acids, and cardiovascular outcomes in patients with type 2 diabetes and acute coronary syndrome

OBJECTIVE: In observational cohorts, adiponectin is inversely associated and free fatty acids (FFAs) are directly associated with incident coronary heart disease (CHD). Adiponectin tends to be reduced and FFAs elevated in type 2 diabetes. We investigated relationships of adiponectin and FFA and major adverse cardiovascular events (MACEs) and death in patients with acute coronary syndrome (ACS) and type 2 diabetes using data from the AleCardio trial, which compared the PPAR-α/γ agonist aleglitazar with placebo. RESEARCH DESIGN AND METHODS: Using Cox regression adjusted for demographic, laboratory, and treatment variables, we determined associations of baseline adiponectin and FFAs, or the change in adiponectin and FFAs from baseline, with MACEs (cardiovascular death, myocardial infarction, or stroke) and death. RESULTS: A twofold higher baseline adiponectin (n = 6,998) was directly associated with risk of MACEs (hazard ratio [HR] 1.17 [95% CI 1.08-1.27]) and death (HR 1.53 [95% CI 1.35-1.73]). A doubling of adiponectin from baseline to month 3 (n = 6,325) was also associated with risk of death (HR 1.20 [95% CI 1.03-1.41]). Baseline FFAs (n = 7,038), but not change in FFAs from baseline (n = 6,365), were directly associated with greater risk of MACEs and death. There were no interactions with study treatment. CONCLUSIONS: In contrast to prior observational data for incident CHD, adiponectin is prospectively associated with MACEs and death in patients with type 2 diabetes and ACS, and an increase in adiponectin from baseline is directly related to death. These findings raise the possibility that adiponectin has different effects in patients with type 2 diabetes and ACS than in populations without prevalent cardiovascular disease. Consistent with prior data, FFAs are directly associated with adverse outcomes

Impact of Age and Sex on Left Ventricular Function Determined by Coronary Computed Tomographic Angiography: Results From the Prospective Multicentre CONFIRM Study

BACKGROUND: Left ventricular (LV) volumetric and functional parameters measured with cardiac computed tomography (cardiac CT) augment risk prediction and discrimination for future mortality. Gender- and age-specific standard values for LV dimensions and systolic function obtained by 64-slice cardiac CT are lacking. METHODS AND RESULTS: 1155 patients from the Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry (54.5% males, mean age 53.1 ± 12.4 years, range: 18-92 years) without known coronary artery disease (CAD), structural heart disease, diabetes, or hypertension who underwent cardiac CT for various indications were categorized according to age and sex. A cardiac CT data acquisition protocol was used that allowed volumetric measuring of LV function. Image interpretation was performed at each site. Patients with significant CAD (>50% stenosis) on cardiac CT were excluded from the analysis. Overall, mean left ventricular ejection fraction (LVEF) was higher in women when compared with men (66.6 ± 7.7% vs. 64.6 ± 8.1%, P 70 years; P 70 years; P < 0.001). CONCLUSION: Our findings indicate that the LV undergoes a lifelong remodelling and highlight the need for age and gender adjusted reference values.info:eu-repo/semantics/publishedVersio

Fractional flow reserve evaluation in patients considered for transfemoral transcatheter aortic valve implantation: a case series

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) has become an established therapy for severe aortic stenosis (AS) in high-risk elderly individuals. Concomitant coronary artery disease (CAD) is frequently encountered in this patient population and may have an impact on outcomes. Hence, in patients with both severe AS and CAD, a bespoke therapy of both AS and/or CAD appears mandatory. METHODS: We report a series of 5 patients with severe AS and concomitant CAD considered for TAVI who underwent fractional flow reserve (FFR) for hemodynamic assessment of coronary lesions. RESULTS: In 3 patients, a 2-staged procedure was undertaken with FFR measurements at the time of invasive assessment and TAVI thereafter. In the remaining 2 patients, FFR measurements were performed immediately prior to the TAVI procedure with deferral of percutaneous coronary intervention (PCI) in one and ad hoc PCI in the other patient. All 5 patients had uneventful FFR measurements and procedural TAVI outcomes. One patient with a staged approach noted a significant improvement in symptoms already after PCI. CONCLUSIONS: FFR provides an effective and safe strategy to assess hemodynamic significance of coronary lesions in patients with severe AS and concomitant CAD considered for TAVI

Post-Discharge Worsening Renal Function in Patients with Type 2 Diabetes and Recent Acute Coronary Syndrome

Background Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge worsening renal function has never been investigated in this setting. Methods We considered the placebo cohort of the AleCardio trial comparing aleglitazar with standard medical therapy among patients with type 2 diabetes mellitus and a recent acute coronary syndrome. Patients who had died or had been admitted to hospital for heart failure before the 6-month follow-up, as well as patients without complete renal function data, were excluded, leaving 2776 patients for the analysis. Worsening renal function was defined as a >20% reduction in estimated glomerular filtration rate from discharge to 6 months, or progression to macroalbuminuria. The Cox regression analysis was used to determine the prognostic impact of 6-month renal deterioration on the composite of all-cause death and hospitalization for heart failure. Results Worsening renal function occurred in 204 patients (7.34%). At a median follow-up of 2 years the estimated rates of death and hospitalization for heart failure per 100 person-years were 3.45 (95% confidence interval [CI], 2.46-6.36) for those with worsening renal function, versus 1.43 (95% CI, 1.14-1.79) for patients with stable renal function. At the adjusted analysis worsening renal function was associated with the composite endpoint (hazard ratio 2.65; 95% CI, 1.57-4.49; P <.001). Conclusions Post-discharge worsening renal function is not infrequent among patients with type 2 diabetes and acute coronary syndromes with normal or mildly depressed renal function, and is a strong predictor of adverse cardiovascular events

Homeostasis model assessment of insulin resistance and survival in patients with diabetes and acute coronary syndrome

Purpose: Insulin resistance has been linked to development and progression of atherosclerosis and is present in most patients with type 2 diabetes (T2D). Whether the degree of insulin resistance predicts adverse outcomes in patients with T2D and acute coronary syndrome (ACS) is uncertain. Methods: The AleCardio trial compared the peroxisome proliferator-activated receptor-α/γ agonist aleglitazar with placebo in patients with T2D and recent ACS. In participants not treated with insulin, we determined whether baseline homeostasis model assessment of insulin resistance (HOMA-IR, n=4303) or the change in HOMA-IR on assigned study treatment (n=3568) was related to the risk of death or major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, and stroke) in unadjusted and adjusted models. Because an inverse association of HOMA-IR with N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been described, we specifically examined effects of adjustment for the latter. Results: In unadjusted analysis, two-fold higher baseline HOMA-IR was associated with lower risk of death (HR 0.79, 95% CI 0.68-0.91, p=0.002). Adjustment for 24 standard demographic and clinical variables had minimal effect on this association. However, after further adjustment for NT-proBNP, the association of HOMA-IR with death was no longer present (adjusted HR 0.99, 95% CI 0.83-1.19, p=0.94). Baseline HOMA-IR was not associated with MACE, nor was the change in HOMA-IR on study treatment associated with death or MACE. Conclusions: After accounting for levels of NT-proBNP, insulin resistance assessed by HOMA-IR is not related to the risk of death or MACE in patients with T2D and ACS