Effect of change in body weight on incident diabetes mellitus in patients with stable coronary artery disease treated with atorvastatin (from the Treating to New Targets Study)

Features of the metabolic syndrome are independent risk factors for new-onset diabetes mellitus (NODM) related to statin therapy. Obesity is the predominant underlying risk factor for the metabolic syndrome and diabetes mellitus. This study investigated whether change in body weight may predict NODM in statin-treated patients. A total of 7,595 patients without prevalent diabetes mellitus at baseline from the Treating to New Targets (TNT) study were included in this analysis. They were randomized to atorvastatin 10 or 80 mg/day and monitored for a median of 4.9 years. NODM developed in 659 patients (8.1% in the 10-mg group and 9.2% in the 80-mg group). There was a significant increase in body weight (0.9 kg, p <0.01 in both men and women) over 1 year after randomization. The increase in body weight was greater in patients with NODM than those without NODM (1.6 vs 0.9 kg, p <0.001). The association of change in body weight with NODM risk remained significant after adjusting for confounding factors (hazard ratios 1.33, 1.42, and 1.88 for quartiles 2, 3, and 4 compared with quartile 1, respectively). Similar results were obtained in patients with normal fasting glucose level. In conclusion, 1-year change in body weight is predictive of NODM in patients who underwent statin therapy from the TNT trial. Our study highlights the importance of weight control as a lifestyle measure to prevent statin-related NODM. © 2014 Elsevier Inc. All rights reserved

Relationship of high-density lipoprotein cholesterol with renal function in patients treated with atorvastatin

Background--It is not known whether the concentration of high-density lipoprotein (HDL) cholesterol is related to renal function in statin-treated patients. We therefore investigated whether HDL cholesterol levels predicted renal function in atorvastatin-treated patients in the TNT (Treating to New Targets) trial. Methods and Results--A total of 9542 participants were included in this analysis. Renal function was assessed by estimated glomerular filtration rate (eGFR). HDL cholesterol levels at month 3 were used as this is the time point at which on-treatment HDL cholesterol levels became stable. Among 6319 participants with a normal eGFR (=60 mL/min per 1.73 m2) at baseline, higher HDL cholesterol levels at month 3 were significantly associated with lower risk of decline in eGFR (ie, having eGFR < 60 mL/min per 1.73 m2) during follow-up (HR of 1.04, 0.88, 0.85, and 0.77 for HDL cholesterol quintiles 2, 3, 4, and 5, respectively, relative to quintile 1, P for trend=0.006). Among 3223 participants with an eGFR (<60 mL/min per 1.73 m2) at baseline, higher HDL cholesterol levels at month 3 had less impact on eGFR during follow-up, with statistical significance observed only when analyzing HDL cholesterol levels as a continuous variable (P=0.043), but not as a categorical quintile variable (P for trend=0.27). Conclusions--In patients treated with atorvastatin, higher HDL cholesterol levels were associated with lower risk of eGFR decline in patients with normal eGFR at baseline. However, further study is needed to establish whether there is any causal relationship between HDLs and renal function. Clinical Trial Registration--URL: https://www.clinicaltrials.gov. Unique identifier: NCT00327691

High plasma FGF21 levels predicts major cardiovascular events in patients treated with atorvastatin (from the Treating to New Targets [TNT] Study)

Background: Higher plasma fibroblast growth factor 21 (FGF21) levels predict incident cardiovascular events in type 2 diabetes patients. However, whether FGF21 levels predict cardiovascular events in statin-treated patients in the general population is unknown. We investigated whether FGF21 levels predict major cardiovascular event (MCVE) in the Treating to New Targets (TNT) trial participants. Methods: After 8-week run-in on atorvastatin 10 mg/day, 10,001 patients with stable coronary disease in the TNT trial were randomized to 10 mg or 80 mg/day of atorvastatin for a median of 4.9 years. We analyzed data from 1996 patients with plasma FGF21 levels measured at randomization. Among them, 1835 patients had FGF21 measured one-year post-randomization. Results: Higher ln-transformed FGF21 levels at randomization were associated with higher risk of incident MCVE (adjusted hazards ratio per SD increase = 1.18, P = 0.019). At 1-year post-randomization, FGF21 levels were lower in patients randomized to receive 80 mg versus 10 mg atorvastatin (186.9 versus 207.5 pg/mL respectively, P = 0.006). Higher ln-transformed FGF21 levels at 1-year post-randomization were also associated with higher subsequent risk of MCVEs (adjusted hazards ratio per SD increase = 1.24, P = 0.009). However, changes in FGF21 levels over 1-year were not related to subsequent MCVE risk. FGF21 levels had significant incremental value in net reclassification improvement in MCVE risk prediction. Conclusions: Higher plasma FGF21 levels are associated with higher CVD risk in statin-treated high-risk patients. Higher dose atorvastatin is associated with a reduction in FGF21 levels. FGF21 provides incremental value in CVD risk prediction in statin-treated patients

Adapted Personalized Cognitive Counseling for Episodic Substance-Using Men Who Have Sex with Men: A Randomized Controlled Trial

Episodic drug use and binge drinking are associated with HIV risk among substance-using men who have sex with men (SUMSM), yet no evidence-based interventions exist for these men. We adapted personalized cognitive counseling (PCC) to address self-justifications for high-risk sex among HIV-negative, episodic SUMSM, then randomized men to PCC (n = 162) with HIV testing or control (n = 164) with HIV testing alone. No significant between-group differences were found in the three primary study outcomes: number of unprotected anal intercourse events (UAI), number of UAI partners, and UAI with three most recent non-primary partners. In a planned subgroup analysis of non-substance dependent men, there were significant reductions in UAI with most recent non-primary partners among PCC participants (RR = 0.56; 95 %CI 0.34–0.92; P = 0.02). We did not find evidence that PCC reduced sexual risk behaviors overall, but observed significant reductions in UAI events among non-dependent SUMSM. PCC may be beneficial among SUMSM screening negative for substance dependence