Parag Anilkumar Chevli, Senthil Selvaraj, Byron C Jaeger
et al.
Abstract Aims Circulating ketone bodies (KB) have emerged as a potential adjunctive biomarker for incident heart failure (HF) risk and might provide incremental information beyond established biomarkers. A multi-marker risk score may improve risk stratification of incident HF in the community. The authors aim to develop a risk score using N-terminal proB-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin (hs-cTnT) and a unique systemic biomarker of KB to predict HF among participants without cardiovascular disease. Methods and results A multi-marker score was developed incorporating NT-proBNP ≥ 125 pg/mL, hs-cTnT ≥ 14 ng/L, and total KB ≥ 75th percentile (316 μmol/L), with one point allocated for each abnormal marker among Multi-Ethnic Study of Atherosclerosis participants. Multivariable Cox model was used to assess the association between multi-marker risk score and the risk of incident HF. Among 6748 participants, there were 383 incident HF events over a median follow-up of 15.7 years. The three biomarkers exhibited poor correlation with one another (r < 0.06 for all). The addition of KB to NT-proBNP and hs-cTnT to identify incident HF improved 5- and 10-year risk prediction (C-statistic 0.74 vs. 0.77, P = 0.02 and 0.70 vs. 0.73, P = 0.02, respectively). There was no evidence of miscalibration using the multi-marker score for predicting 5- and 10-year HF risk (P > 0.05). A graded association was observed between the multi-marker score and risk of HF independent of established clinical factors. Conclusion The addition of plasma KB to a clinical risk score using biomarkers of cardiac injury and stress may further improve the prediction of incident HF.
OBJECTIVE In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, ∼4 years of intensive versus standard glycemic control in participants with type 2 diabetes and other cardiovascular risk factors had a neutral effect on the composite cardiovascular outcome, increased cardiovascular and total mortality, and reduced nonfatal myocardial infarction. Effects of the intervention during prolonged follow-up were analyzed. RESEARCH DESIGN AND METHODS All surviving ACCORD participants were invited to participate in the ACCORD Follow-on (ACCORDION) study, during which participants were treated according to their health care provider’s judgment. Cardiovascular and other health-related outcomes were prospectively collected and analyzed using an intention-to-treat approach according to the group to which participants were originally allocated. RESULTS A total of 8,601 people, representing 98% of those who did not suffer a primary outcome or death during the ACCORD trial, were monitored for a median of 8.8 years and a mean of 7.7 years from randomization. Intensive glucose lowering for a mean of 3.7 years had a neutral long-term effect on the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), death from any cause, and an expanded composite outcome that included all-cause death. Moreover, the risk of cardiovascular mortality noted during the active phase (hazard ratio 1.49; 95% CI 1.19, 1.87; P < 0.0001) decreased (HR 1.20; 95% CI 1.03, 1.39; P = 0.02). CONCLUSIONS In high-risk people with type 2 diabetes monitored for 9 years, a mean of 3.7 years of intensive glycemic control had a neutral effect on death and nonfatal cardiovascular events but increased cardiovascular-related death.
Chuan Gao, Carl D. Langefeld, Julie T. Ziegler
et al.
ObjectiveThis study aimed to explore the genetic mechanisms of regional fat deposition, which is a strong risk factor for metabolic diseases beyond total adiposity.MethodsA genome‐wide association study of 7,757,139 single‐nucleotide polymorphisms (SNPs) in 983 Mexican Americans (nmale = 403; nfemale = 580) from the Insulin Resistance Atherosclerosis Family Study was performed. Association analyses were performed with and without sex stratification for subcutaneous adipose tissue, visceral adipose tissue (VAT), and visceral‐subcutaneous ratio (VSR) obtained from computed tomography.ResultsThe strongest signal identified was SNP rs2185405 (minor allele frequencies [MAF] = 40%; PVAT = 1.98 × 10−8) with VAT. It is an intronic variant of the GLIS family zinc finger 3 gene (GLIS3). In addition, SNP rs12657394 (MAF = 19%) was associated with VAT in males (Pmale = 2.39×10−8; Pfemale = 2.5 × 10−3). It is located intronically in the serum response factor binding protein 1 gene (SRFBP1). On average, male carriers of the variant had 24.6 cm2 increased VAT compared with noncarriers. Subsequently, genome‐wide SNP‐sex interaction analysis was performed. SNP rs10913233 (MAF = 14%; Pint = 3.07 × 10−8) in PAPPA2 and rs10923724 (MAF = 38%; Pint = 2.89 × 10−8) upstream of TBX15 were strongly associated with the interaction effect for VSR.ConclusionsSix loci were identified with genome‐wide significant associations with fat deposition and interactive effects. These results provided genetic evidence for a differential basis of fat deposition between genders.