• cardiovascular disease
• cholecalciferol
• outcome
• pathophysiology
• vitamin D

• 25-hydroxy-vitamin D
• meta-analysis
• stroke

Vitamin D deficiency is a prevalent condition, occurring in about 30–50% of the population, observed across all ethnicities and among all age groups. Besides the established role of vitamin D in calcium homeostasis, its deficiency is emerging as a new risk factor for cardiovascular disease (CVD). In particular, several epidemiological and clinical studies have reported a close association between low vitamin D levels and major CVDs, such as coronary artery disease, heart failure, and atrial fibrillation. Moreover, in all these clinical settings, vitamin deficiency seems to predispose to increased morbidity, mortality, and recurrent cardiovascular events. Despite this growing evidence, interventional trials with supplementation of vitamin D in patients at risk of or with established CVD are still controversial. In this review, we aimed to summarize the currently available evidence supporting the link between vitamin D deficiency and major CVDs in terms of its prevalence, clinical relevance, prognostic impact, and potential therapeutic implications.

• atrial fibrillation
• cardiovascular disease
• coronary artery disease
• heart failure
• prevalence
• prognosis
• vitamin D

• Cardiovascular Diseases/drug therapy
• Dietary Supplements
• Humans
• Platelet Aggregation Inhibitors/therapeutic use
• Vitamin D/therapeutic use

• Metabolic syndrome
• Polymorphism
• Serum 25(OH)D
• VDR

• Coronary heart disease
• Genotyping
• Restenosis
• SNP

• Coronary Artery Disease/epidemiology
• Genotype
• Heterozygote
• Homozygote
• Humans
• Polymorphism, Genetic
• Receptors, Calcitriol/genetics
• Risk

• Atherosclerosis
• Coronary artery disease
• Genetics
• Genome-wide association study
• Heritability
• In-stent restenosis
• Myocardial infarction

• T32 HL083828 NHLBI NIH HHS

Dialysis patients have high cardiovascular mortality risk. This study aimed to investigate the association between SNPs of genes involved in vascular processes and mortality in dialysis patients.

Forty two SNPs in 25 genes involved in endothelial function, vascular remodeling, cell proliferation, inflammation, coagulation and calcium/phosphate metabolism were genotyped in 1330 incident dialysis patients. The effect of SNPs on 5-years cardiovascular and non-cardiovascular mortality was investigated.

The mortality rate was 114/1000 person-years and 49.4% of total mortality was cardiovascular. After correction for multiple testing, VEGF rs699947 was associated with all-cause mortality (HR1.48, 95% CI 1.14–1.92). The other SNPs were not associated with mortality.

This study provides further evidence that a SNP in the VEGF gene may contribute to the comorbid conditions of dialysis patients. Future studies should unravel the underlying mechanisms responsible for the increase in mortality in these patients.

We sought to identify gene polymorphisms that confer susceptibility to in-stent restenosis after coronary artery bare-metal stenting in a Central European population.

160 controls without post–percutaneous coronary intervention in-stent restenosis were matched for age, sex, vessel diameter, and diabetes to 160 consecutive cases involving in-stent restenosis of the target lesion within 12 months. Using real time polymerase chain reaction and melting-curve analysis, we detected 13 single-nucleotide polymorphisms in 11 candidate genes - rs1803274 (BCHE gene), rs529038 (ROS1), rs1050450 (GPX1), rs1800849 (UCP3), rs17216473 (ALOX5AP), rs7412, rs429358 (ApoE), rs2228570 (VDR), rs7041, rs4588 (GC), rs1799986 (LRP1) and rs2228671 (LDLR). Multivariable logistic regression was used to test for associations.

The rs1803274 polymorphism of BCHE was significantly associated with in-stent restenosis (OR 1.934; 95 % CI: 1.181–3.166; p = 0.009). No association was found with the other studied SNPs.

The A allele of rs1803274 represents a risk factor for in-stent restenosis in Central European patients after percutaneous coronary intervention with bare-metal stent implantation.

• Acute Coronary Syndrome/blood
• Acute Coronary Syndrome/mortality
• Aged
• Aged, 80 and over
• Comorbidity
• Female
• Hospital Mortality
• Humans
• Male
• Middle Aged
• Prognosis
• Prospective Studies
• Risk Factors
• Vitamin D/analogs & derivatives
• Vitamin D/blood
• Vitamin D Deficiency/epidemiology

• Acute Coronary Syndrome/drug therapy
• Acute Coronary Syndrome/etiology
• Acute Coronary Syndrome/physiopathology
• Blood Platelets/physiology
• Coronary Artery Disease/drug therapy
• Coronary Artery Disease/etiology
• Coronary Artery Disease/physiopathology
• Endothelial Cells/physiology
• Humans
• Inflammation/physiopathology
• Risk Factors
• Vascular Calcification/physiopathology
• Vascular Stiffness
• Vitamin D/physiology
• Vitamin D/therapeutic use
• Vitamin D Deficiency/complications
• Vitamin D Deficiency/drug therapy
• Vitamin D Deficiency/physiopathology
• Vitamins/therapeutic use

• R01 HL034594 NHLBI NIH HHS

Coronary restenosis after percutaneous coronary intervention still remains a significant problem, despite all medical advances. Unraveling the mechanisms leading to restenosis development remains challenging. Many studies have identified genetic markers associated with restenosis, but consistent replication of the reported markers is scarce. The aim of the current study was to analyze the joined effect of previously in literature reported candidate genes for restenosis in the GENetic DEterminants of Restenosis (GENDER) databank.

Candidate genes were selected using a MEDLINE search including the terms ‘genetic polymorphism’ and ‘coronary restenosis’. The final set included 36 genes. Subsequently, all single nucleotide polymorphisms (SNPs) in the genomic region of these genes were analyzed in GENDER using set-based analysis in PLINK. The GENDER databank contains genotypic data of 2,571,586 SNPs of 295 cases with restenosis and 571 matched controls. The set, including all 36 literature reported genes, was, indeed, significantly associated with restenosis, p = 0.024 in the GENDER study. Subsequent analyses of the individual genes demonstrated that the observed association of the complete set was determined by 6 of the 36 genes.

Despite overt inconsistencies in literature, with regard to individual candidate gene studies, this is the first study demonstrating that the joint effect of all these genes together, indeed, is associated with restenosis.

Dysregulation of microRNA (miRNA) expression has been implicated in molecular genetic events leading to the progression and development of atherosclerosis. We hypothesized that miRNA expression profiles differ between baboons with low and high serum low-density lipoprotein cholesterol (LDL-C) concentrations in response to diet, and that a subset of these miRNAs regulate genes relevant to dyslipidemia and risk of atherosclerosis.

Using Next Generation Illumina sequencing methods, we sequenced hepatic small RNA libraries from baboons differing in their LDL-C response to a high-cholesterol, high-fat (HCHF) challenge diet (low LDL-C, n = 3; high LDL-C, n = 3), resulting in 517 baboon miRNAs: 490 were identical to human miRNAs and 27 were novel. We compared miRNA expression profiles from liver biopsies collected before and after the challenge diet and observed that HCHF diet elicited expression of more miRNAs compared to baseline (chow) diet for both low and high LDL-C baboons. Eighteen miRNAs exhibited differential expression in response to HCHF diet in high LDL-C baboons compared to 10 miRNAs in low LDL-C baboons. We used TargetScan/Base tools to predict putative miRNA targets; miRNAs expressed in high LDL-C baboons had significantly more gene targets than miRNAs expressed in low LDL-C responders. Further, we identified miRNA isomers and other non-coding RNAs that were differentially expressed in response to the challenge diet in both high LDL-C and low LDL-C baboons.

We sequenced and annotated baboon liver miRNAs from low LDL-C and high LDL-C responders using high coverage Next Gen sequencing methods, determined expression changes in response to a HCHF diet challenge, and predicted target genes regulated by the differentially expressed miRNAs. The identified miRNAs will enrich the database for non-coding small RNAs including the extent of variation in these sequences. Further, we identified other small non-coding RNAs differentially expressed in response to diet. Our discovery of differentially expressed baboon miRNAs in response to a HCHF diet challenge that differ by LDL-C phenotype is a fundamental step in understating the role of non-coding RNAs in dyslipidemia.