PPAR genomics and pharmacogenomics: Implications for cardiovascular disease

The peroxisome proliferator-activated receptors (PPARs) consist of three related transcription factors that serve to regulate a number of cellular processes that are central to cardiovascular health and disease. Numerous pharmacologic studies have assessed the effects of specific PPAR agonists in clinical trials and have provided insight into the clinical effects of these genes while genetic studies have demonstrated clinical associations between PPAR polymorphisms and abnormal cardiovascular phenotypes. With the abundance of data available from these studies as a background, PPAR pharmacogenetics has become a promising and rapidly advancing field. This review focuses on summarizing the current state of understanding of PPAR genetics and pharmacogenetics and the important implications for the individualization of therapy for patients with cardiovascular diseases

Slow gait speed and cardiac rehabilitation participation in older adults after acute myocardial infarction

Background Lack of participation in cardiac rehabilitation ( CR ) and slow gait speed have both been associated with poor long‐term outcomes in older adults after acute myocardial infarction ( AMI ). Whether the effect of CR participation on outcomes after AMI differs by gait speed is unknown. Methods and Results We examined the association between gait speed and CR participation at 1 month after discharge after AMI , and death and disability at 1 year, in 329 patients aged ≥65 years enrolled in the TRIUMPH (Translational Research Investigating Underlying Disparities in Recovery From Acute Myocardial Infarction: Patients' Health Status) registry. Among these patients, 177 (53.7%) had slow gait speed (&lt;0.8 m/s) and 109 (33.1%) participated in CR . Patients with slow gait speed were less likely to participate in CR compared with patients with normal gait speed (27.1% versus 40.1%; P =0.012). In unadjusted analysis, CR participants with normal gait speed had the lowest rate of death or disability at 1 year (9.3%), compared with those with slow gait speed and no CR participation (43.2%). After adjustment for cardiovascular risk factors and cognitive impairment, both slow gait speed (odds ratio, 2.30; 95% confidence interval, 1.30–4.06) and non‐ CR participation (odds ratio, 2.34; 95 confidence interval, 1.22–4.48) were independently associated with death or disability at 1 year. The effect of CR on the primary outcome did not differ by gait speed ( P =0.70). Conclusions CR participation is associated with reduced risk for death or disability after AMI . The beneficial effect of CR participation does not differ by gait speed, suggesting that slow gait speed alone should not preclude referral to CR for older adults after AMI . </jats:sec

Recurrent takotsubo cardiomyopathy in a patient with hypertrophic cardiomyopathy leading to cardiogenic shock requiring VA-ECMO

Providing hemodynamic support for patients with hypertrophic cardiomyopathy and cardiogenic shock can be challenging because inotropic medications worsen intraventricular obstruction, and the effect of appropriate mechanical support remains undefined. We report a patient with hypertrophic cardiomyopathy in shock because of takotsubo cardiomyopathy requiring venoarterial extracorporeal membrane oxygenation and septal reduction for full recovery.

Factors influencing patient willingness to participate in genetic research after a myocardial infarction

Abstract Background Achieving 'personalized medicine' requires enrolling representative cohorts into genetic studies, but patient self-selection may introduce bias. We sought to identify characteristics associated with genetic consent in a myocardial infarction (MI) registry. Methods We assessed correlates of participation in the genetic sub-study of TRIUMPH, a prospective MI registry (n = 4,340) from 24 US hospitals between April 2005 and December 2008. Factors examined included extensive socio-demographics factors, clinical variables, and study site. Predictors of consent were identified using hierarchical modified Poisson regression, adjusting for study site. Variation in consent rates across hospitals were quantified by the median rate ratio (MRR). Results Most subjects consented to donation of their genetic material (n = 3,484; 80%). Participation rates varied greatly between sites, from 40% to 100%. After adjustment for confounding factors, the MRR for hospital was 1.22 (95% confidence interval (CI) 1.11 to 1.29). The only patient-level factors associated with consent were race (RR 0.93 for African Americans versus whites, 95% CI 0.88 to 0.99) and body mass index (RR 1.03 for BMI &#8805; 25, 95% CI 1.01 to 1.06). Conclusion Among patients with an MI there were notable differences in genetic consent by study site, but little association with patient-level factors. This suggests that variation in the way information is presented during recruitment, or other site factors, strongly influence patients' decision to participate in genetic studies.Peer Reviewe

Inequities in treatments and outcomes among patients hospitalized with hypertrophic cardiomyopathy in the United States

Background Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disease. In small studies, sociodemographic factors have been associated with disparities in septal reduction therapy, but little is known about the association of sociodemographic factors with HCM treatments and outcomes more broadly. Methods and Results Using the National Inpatient Survey from 2012 to 2018, HCM diagnoses and procedures were identified b

The supernova rate in local galaxy clusters

We report a measurement of the supernova (SN) rates (Ia and core-collapse) in galaxy clusters based on the 136 SNe of the sample described in Cappellaro et al. (1999) and Mannucci et al. (2005). Early-type cluster galaxies show a type Ia SN rate (0.066 SNuM) similar to that obtained by Sharon et al. (2007) and more than 3 times larger than that in field early-type galaxies (0.019 SNuM). This difference has a 98% statistical confidence level. We examine many possible observational biases which could affect the rate determination, and conclude that none of them is likely to significantly alter the results. We investigate how the rate is related to several properties of the parent galaxies, and find that cluster membership, morphology and radio power all affect the SN rate, while galaxy mass has no measurable effect. The increased rate may be due to galaxy interactions in clusters, inducing either the formation of young stars or a different evolution of the progenitor binary systems. We present the first measurement of the core-collapse SN rate in cluster late-type galaxies, which turns out to be comparable to the rate in field galaxies. This suggests that no large systematic difference in the initial mass function exists between the two environments.Comment: MNRAS, revised version after referee's comment