Endothelial apoptosis is the core pathological change in atherosclerotic cardiovascular disease, including coronary artery disease (CAD). Determining the molecular mechanisms underlying endothelial apoptosis is important. Nuclear factor kappa B (NF‐κB) is a crucial transcription factor for controlling apoptosis. Our previous study demonstrated that the ‐94 ATTG ins/del mutant in the promoter of NFKB1 gene (rs28362491) is a risk factor for CAD. In the present study, we found that NFKB1 rs28362491 polymorphism was positively associated with increased major adverse cardiac and cerebrovascular events (MACCEs) in CAD patients. After adjusting for confounding factors including age, smoking, hypertension, glucose, and low‐density lipoprotein cholesterol, the mutant DD genotype was an independent predictor of MACCEs (OR = 2.578, 95%CI = 1.64–4.05, P = 0.003). The in vitro study showed that mutant human umbilical vein endothelial cells (DD‐mutant HUVECs) were more susceptible to high‐glucose/palmitate‐induced apoptosis, which was accompanied by decreased p50 expression and increased expression of cleaved caspase‐3, Cytochrome c, and phospho‐p65 (P < 0.05). The mitochondrial membrane potential was significantly lower, while increasing levels of mtROS and more opening of the mPTP were observed in DD‐mutant HUVECs (P < 0.05). Furthermore, the percentage of cells with fragmented or spherical mitochondria was significantly higher in DD‐mutant HUVECs than in wild‐type cells (genotype II HUVECs) (P < 0.05). In addition, after stimulation with high glucose/palmitate, the NFKB1 gene mutant significantly increased the expression of Drp1, which indicated that the NFKB1 gene mutant affected the expression of mitochondrial morphology‐related proteins, leading to excessive mitochondrial fission. In conclusion, the mutant DD genotype of the NFKB1 gene was an independent predictor of worse long‐term prognosis for CAD patients. DD‐mutant HUVECs exhibited abnormal activation of the NF‐κB pathway and increased Drp1 expression, which caused excessive mitochondrial fission and dysfunction, ultimately leading to increased apoptosis.

CCN1 plays a crucial role in the modulation of cardiovascular diseases. However, whether CCN1 genetic variants are involved in the susceptibility of ACS remains unknown. Hence, the present study investigates the association between CCN1 polymorphisms and ACS among Han and Uygur populations in Xinjiang, China. In this case-control study, 1234 Han (547 ACS patients and 687 controls) and 932 Uygur (471 ACS patients and 461 controls) were genotyped using SNPscan^TM for three single-nucleotide polymorphisms (SNPs, rs6576776, rs954353, and rs3753794) of the human CCN1 gene. In the Uygur population, we found that the detected frequencies of the C allele (25.3% vs. 18.3%, P<0.001) and CC genotype (6.4% vs. 3.0%, P=0.001) of rs6576776 were significantly higher in the ACS patients than in the control participants. Differences in rs6576776 regarding the dominant model (CC+CG vs. GG, 44.2% vs. 55.8%, P=0.001) and the recessive model (CC vs. CG+GG, 6.4% vs. 93.6%, P=0.016) were observed between the two groups. The frequencies of the GGC and AGC haplotypes in those with ACS were significantly higher than those in the control group (all P<0.05) in the Uygur population. After adjusting for hypertension, diabetes, lipids and smoking, all of which indicate that the rs6576776 C allele is associated with higher risk of ACS (odds ratio (OR)=1.798, 95% confidence interval (CI), 1.218-2.656, P=0.003). In Han population, neither the distribution of genotypes and alleles of the CCN1 gene three SNPs nor the distribution of haplotypes constructed with the three SNPs exhibited a significant difference between the ACS patients and control participants. Our study document that the CCN1 gene rs6576776 C allele is associated with higher susceptibility of ACS and that the frequencies of GGC and AGC haplotypes are higher among the Uygur ACS patients.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Left ventricular hypertrophy (LVH) is an important marker of cardiovascular risk, while malnutrition is common among adults. The Controlling Nutritional Status (CONUT) score is an objective tool for nutritional assessment. This study aimed to investigate the associations of CONUT-defined nutritional status with LVH and reduced left ventricular ejection fraction (LVEF) in adults. This single-center retrospective cross-sectional study included 2066 adults. Nutritional status was classified according to the standard CONUT categories as normal nutrition, mild malnutrition, and moderate/severe malnutrition. Echocardiography was used to assess left ventricular mass index and LVEF, and LVH was defined using sex-specific left ventricular mass index thresholds. Logistic regression analyses were performed to evaluate the associations of CONUT-defined nutritional status with LVH and reduced LVEF. Among the 2066 participants, 1002 (48.5%) had normal nutritional status, 912 (44.1%) had mild malnutrition, and 152 (7.4%) had moderate/severe malnutrition. In the multivariable logistic regression model, both mild malnutrition (odds ratio [OR] = 1.597, 95% confidence interval [CI]: 1.033–2.495; P = .037) and moderate/severe malnutrition (OR = 2.810, 95% CI: 1.445–5.223; P = .002) were independently associated with higher odds of LVH. Moderate/severe malnutrition was independently associated with reduced LVEF (OR = 2.350, 95% CI: 1.259–4.239; P = .006). Poorer CONUT-defined nutritional status was associated with a higher prevalence of left ventricular structural and functional abnormalities. CONUT-defined nutritional status may provide supplementary information for cardiovascular risk stratification.