The latest medical research on Atrial Fibrillation

Older patients with chronic kidney disease (CKD) are more likely to be excluded from clinical trials. This exclusion affects the quality of cardiovascular disease (CVD) prevention in this population.

Baseline data from the Fukuoka Kidney Disease Registry (FKR) cohort, which included 4476 adult patients with CKD stages G1-G5, were cross-sectionally analyzed to compare the use of recommended drugs for preventing CVD in each age group.

Different prescribing patterns were observed according to age for the cardiovascular drug classes. Older patients with CKD were less likely to receive renin-angiotensin system (RAS) inhibitors and were more likely to receive calcium channel blockers. The proportion of anticoagulation prescriptions for patients with CKD and atrial fibrillation decreased in the older age group (≥ 75 years). However, the proportion of antiplatelet therapy in patients with ischemic CVD increased linearly with age, even in the very old group aged ≥ 85 years. These findings suggest a severe cardiovascular burden in patients with CKD. Notably, RAS inhibitor use was avoided in the older group despite a severe cardiovascular burden, such as a high prevalence of CVD history and massive albuminuria ＞300 mg/g creatinine. This finding indicates that an older age independently contributed to the non-use of RAS inhibitors, even after adjusting for other covariates.

This study suggests that age is a potential barrier to the treatment of patients with CKD and highlights the need to establish individualized treatment strategies for cardiovascular protection in this population.

LCZ696 (sacubitril/valsartan) exerts cardioprotective effects. Recent studies have suggested that it improves the endothelial function; however, the underlying mechanisms have not been thoroughly investigated. We investigated whether LCZ696 ameliorates diabetes-induced endothelial dysfunction.

Diabetes was induced using streptozotocin in 8-week-old male C57BL/6 mice. Diabetic mice were randomly assigned to receive LCZ696 (100 mg/kg/day), valsartan (50 mg/kg/day), or a vehicle for three weeks. The endothelium-dependent and endothelium-independent vascular responses of the aortic segments were determined based on the response to acetylcholine and sodium nitroprusside, respectively. Human umbilical vein endothelial cells (HUVEC) and aortic segments obtained from C57BL/6 mice were used to perform in vitro and ex vivo experiments, respectively.

LCZ696 and valsartan reduced the blood pressure in diabetic mice (P＜0.05). The administration of LCZ696 (P＜0.001) and valsartan (P＜0.01) ameliorated endothelium-dependent vascular relaxation, but not endothelium-independent vascular relaxation, under diabetic conditions. LCZ696, but not valsartan, increased eNOSSer1177 (P=0.06) and Akt (P＜0.05) phosphorylation in the aorta. In HUVEC, methylglyoxal (MGO), a major precursor of advanced glycation end products, decreased eNOSSer1177 phosphorylation (P＜0.05) and increased eNOSThr495 phosphorylation (P＜0.001). However, atrial natriuretic peptide (ANP) reversed these effects. ANP also ameliorated the MGO-induced impairment of endothelium-dependent vascular relaxation in the aortic segments (P＜0.05), although L-NAME completely blocked this effect (P＜0.001).

LCZ696 ameliorated diabetes-induced endothelial dysfunction by increasing the bioavailability of ANP. Our findings suggest that LCZ696 has a vascular protective effect in a diabetic model and highlight that it may be more effective than valsartan.

Evidence regarding the modification effects of age, sex, ethnicity, socioeconomic status, or weight status on the associations of sedentary behavior (SB) with cardiovascular diseases (CVDs) is limited. Moreover, the mechanisms for the associations also remain unclear. We aimed to investigate the possible influence of these factors on the associations of SB with CVD events and whether the associations are mediated by metabolic phenotypes.

This study included 42,619 participants aged 20-74 years, recruited from the Shanghai Suburban Adult Cohort and Biobank study. SB was assessed at baseline and integrated with health information systems to predict future CVD events. Cox proportional hazards models, interaction analyses, restricted cubic splines and causal mediation analyses were used for assessments.

Compared to those with ＜3 h/d sedentary time, participants having SB ≥ 5 h/d had significantly higher risks of CVD (HR[95%CI]: 1.27[1.12-1.44]), coronary heart disease (CHD, 1.35[1.14-1.60]), and ischemic stroke (IS, 1.30[1.06-1.60]). The association of CHD was more pronounced in the retired individuals than their counterparts (1.45[1.20-1.76] versus 1.06[0.74-1.52], pinteraction=0.046). When SB was expressed as a continuous variable, a 1 h/d increment in SB was positively associated with risks of CVD (1.03[1.01-1.05]), CHD (1.04[1.01-1.07]), and IS (1.05[1.01-1.08]). High-density lipoprotein cholesterol (HDL-C, proportion mediated: 12.54%, 12.23%, and 11.36%, all p＜0.001), followed by triglyceride (TG, 5.28%, 4.77%, and 4.86%, all p＜0.01) and serum uric acid (SUA, 3.64%, 4.24%, and 2.29%, all p＜0.05) were major mediators through metabolic phenotypes.

Higher SB was associated with elevated risks of CVD events. The detrimental effect of SB on CHD risk was more pronounced among retired individuals. Moreover, HDL-C, TG and SUA partially mediated the relationships between SB and CVD events. Our findings may have implications for preventing and controlling CVD associated with SB.