Dietary Glycemic Index, Glycemic Load, and Risk of Coronary Heart Disease, Stroke, and Stroke Mortality: A Systematic Review with Meta-Analysis

Background: The relationship between dietary glycemic index, glycemic load and risk of coronary heart disease (CHD), stroke, and stroke-related mortality is inconsistent. Methods: We systematically searched the MEDLINE, EMBASE, and Science Citation Index Expanded databases using glycemic index, glycemic load, and cardiovascular disease and reference lists of retrieved articles up to April 30, 2012. We included prospective studies with glycemic index and glycemic load as the exposure and incidence of fatal and nonfatal CHD, stroke, and stroke-related mortality as the outcome variable. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models. Results: Fifteen prospective studies with a total of 438,073 participants and 9,424 CHD cases, 2,123 stroke cases, and 342 deaths from stroke were included in the meta-analysis. Gender significantly modified the effects of glycemic index and glycemic load on CHD risk, and high glycemic load level was associated with higher risk of CHD in women (RR = 1.49, 95%CI 1.27−1.73), but not in men (RR = 1.08, 95%CI 0.91−1.27). Stratified meta-analysis by body mass index indicated that among overweight and obese subjects, dietary glycemic load level were associated with increased risk of CHD (RR = 1.49, 95%CI 1.27−1.76; P for interaction = 0.003). Higher dietary glycemic load, but not glycemic index, was positively associated with stroke (RR = 1.19, 95% CI 1.00−1.43). There is a linear dose-response relationship between dietary glycemic load and increased risk of CHD, with pooled RR of 1.05 (95%CI 1.02−1.08) per 50-unit increment in glycemic load level. Conclusion: High dietary glycemic load is associated with a higher risk of CHD and stroke, and there is a linear dose-response relationship between glycemic load and CHD risk. Dietary glycemic index is slightly associated with risk of CHD, but not with stroke and stroke-related death. Further studies are needed to verify the effects of gender and body weight on cardiovascular diseases

Prevalence and risk factors of abnormal left ventricular geometrical patterns in untreated hypertensive patients

BACKGROUND: The various prevalence of LVH and abnormal LV geometry have been reported in different populations. So far, only a few reports are available on the prevalence of LV geometric patterns in a large Chinese untreated hypertensive population. METHODS: A total of 9,286 subjects (5167 men and 4119 women) completed the survey and 1641 untreated hypertensive patients (1044 males and 597 females) enrolled in the present study. The LV geometry was classified into four patterns: normal; abnormal,defined as concentric remodeling;concentric or eccentric hypertrophy based on the values of left ventricular mass index (LVMI) and relative wall thickness (RWT). Logistic regression model was applied to determine the odds ratio (OR) and 95% confidence intervals (CI) of the risk factors of left ventricular hypertrophy. RESULTS: The prevalence of LVH was 20.2% in untreated hypertensive patients, much higher in women (30.8%) than in men (14.2%) (P < 0.01). The prevalence of LV geometrical patterns was 34.9%, 11.1%, 9.1% for concentric remodeling, concentric and eccentric hypertrophy,respectively. After adjustment by using Logistic regression model, the risk factors for LVH and abnormal LV geometry were age, female, systolic blood pressure, and body mass index. And low high density lipoprotein maybe a positive factor. CONCLUSIONS: The prevalence of LVH and abnormal LV geometric patterns was higher in women than in men and increased with age. It is crucial to improve the awareness rate of hypertension and control the risk factors of CV complications in untreated hypertensive population

Functional Haplotypes of the hTERT Gene, Leukocyte Telomere Length Shortening, and the Risk of Peripheral Arterial Disease

Background: The development of peripheral arterial disease (PAD) is heterogeneous even in the presence of similar risk factors. Our aim was to determine whether inter-individual differences in leukocyte telomere length contribute to the susceptibility of PAD. Methods A total of 485 patients with PAD (defined by the ankle-brachial index) and 970 age- and gender-matched controls were recruited from seven rural communities in Henan Province in China. The relative leukocyte telomere length was determined by a quantitative PCR-based method. Two common promoter variants of the hTERT gene were genotyped to assess their effects on telomere length and the risk of PAD. In vivo luciferase assay was performed to study the transcriptional activity. Results: After adjustment for vascular risk factors and genetic variants in the hTERT gene, individuals in the lowest and middle tertiles of telomere length had a significantly higher risk of PAD than did those in the highest tertile (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.29–2.49 in the middle tertile; 3.15, 95%CI 2.31–4.29 in the lowest tertile). Haplotype analysis using the 2 variants (rs2735940 and rs2853669) showed that subjects with the at-risk C-C haplotype had shorter telomere length than those individuals with the T-T haplotype and consistently had 1.30-fold (OR 1.30, 95%CI 1.06–1.58; P = 0.005) increased risk for PAD. The C-C haplotype had 43% lowered transcription activity of hTERT promoter (P<0.001). Conclusion: The associations between the functional haplotype of hTERT gene and telomere length and the risk of atherosclerotic PAD suggested that mean leukocyte telomere length may independently serve as a potential predictor of PAD

Interaction of functional NPC1 gene Polymorphism with smoking on coronary heart disease

<p>Abstract</p> <p>Background</p> <p>The protein of Niemann-pick type C1 gene (<it>NPC1</it>) is known to facilitate the egress of cholesterol and other lipids from late endosomes and lysosomes to other cellular compartments. This study aims to investigate whether the genetic variation in <it>NPC1 </it>is associated with risk of coronary heart disease (CHD) and to detect whether <it>NPC1 </it>might interact with smoking on the risk of CHD.</p> <p>Methods</p> <p>We performed a case-control study, including 873 patients with coronary heart disease (CHD) and 864 subjects without CHD as control. Polymorphisms of <it>NPC1 </it>gene were genotyped by polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP).</p> <p>Results</p> <p>A tag-SNP rs1805081 (+644A > G) in <it>NPC1 </it>was identified. The G allele of the +644 locus showed reduced risk of CHD than wild-type genotype in Chinese population (recessive model GG vs. AG+AA: odds ratio [OR] 0.647, 95% CI 0.428 to 0.980, <it>P </it>= 0.039; additive model GG vs. AG vs. AA: OR 0.847, 95% CI 0.718 to 0.998, <it>P </it>= 0.0471). Moreover in smokers, the G-allele carriers had reduced risk of CHD compared with A-allele carries (OR 0.552, 95% CI 0.311 to 0.979, <it>P </it>= 0.0421).</p> <p>Conclusions</p> <p>The results of the present study suggest that <it>NPC1 </it>variants seem to be contributors to coronary heart disease occurrence in Chinese population. Moreover, in smokers, <it>NPC1 </it>variants seem to confer protection to coronary heart disease.</p

A functional variant in promoter region of platelet-derived growth factor-D is probably associated with intracerebral hemorrhage

<p>Abstract</p> <p>Background</p> <p>Platelet-derived growth factor D (PDGF-D) plays an important role in angiogenesis, vessel remodeling, inflammation and repair in response to injury. We hypothesized that genetic variation in <it>PDGFD </it>gene might alter the susceptibility to stroke.</p> <p>Findings</p> <p>We determined the genotypes of a single nucleotide polymorphism (SNP) (-858A/C, rs3809021) in 1484 patients with stroke (654 cerebral thrombosis, 419 lacunar infarction, 411 intracerebral hemorrhage [ICH]) and 1528 control subjects from an unrelated Chinese Han population and followed the stroke patients up for a median of 4.5 years.</p> <p>The -858AA genotype showed significantly increased risk of ICH (dominant model: odds ratio [OR] 1.29, 95% confidence interval [CI] 1.00-1.68, <it>P </it>= 0.05; additive model: OR 1.24, 95% CI 1.01-1.52, <it>P </it>= 0.04) than wild-type genotype. Further analyses showed that -858AA genotype conferred about 2-fold increase in risk of non-hypertensive ICH (dominant model: OR 2.1, 95%CI 1.34-3.29, <it>P </it>= 0.001; additive model: OR 1.75, 95% CI 1.24-2.46, <it>P </it>= 0.001). After a median follow-up of 4.5 years, -858AA genotype was associated with a reduced risk of ICH recurrence (dominant model: adjusted hazard ratio [HR] 0.09, 95%CI 0.01-0.74, P = 0.025; additive model: HR 0.21, 95% CI 0.04-1.16, <it>P </it>= 0.073) in non-hypertensive patients.</p> <p>Conclusions</p> <p>The -858AA genotype is probably associated with risk for non-hypertensive ICH. Further studies should be conducted to reveal the role of PDGF-D at various stages of ICH development--beneficial, or deleterious.</p

DNA methylation in the norepinephrine transporter gene promoter region is not associated with depression and hypertension

Objective: This study aims to detect the role of DNA methylation in norepinephrine transporter (NET) gene promoter region on the association between depression and hypertension. Methods: A total of 162 subjects were categorized into four groups based on depression scores and blood pressure. DNA was extracted from peripheral white blood cells and methylation levels of nine CpG sites in NET gene promoter region were investigated by pyrosequencing. Results: For each CpG site and the average value of nine CpG sites, there were no significant differences in DNA methylation of the NET gene promoter between healthy controls and patients with depression or hypertension. And there were no significant differences among groups after adjusting for age and body mass index. However, DNA methylation levels of the CpG sites adjacent to transcription start site tended to be low. In addition, CpG1.2–CpG5.2 were highly correlated with CpG4 as the first principle component, while CpG2 and the part of CpG1 and 3 were the second principle components. The total participants were clustered into three subgroups by hierarchical cluster analysis of methylated levels. Conclusion: Our study indicates that DNA methylation levels of nine CpG sites in NET gene promoter region are not associated with depression and hypertension

Prevalence and characteristics of apparent treatment-resistant hypertension in older people in China: a cross-sectional study

The prevalence and associated risk factors of apparent treatment-resistant hypertension (aTRH) in older people in China is unknown. The aim of this study is to investigate the prevalence of aTRH in older people and describe the characteristics of older patients with aTRH. Using two-stage random clustering sampling, 3774 patients with hypertension aged ≥60–75 years were recruited between July 2012 and December 2015. The patients were divided into two groups: aTRH and non-aTRH groups according to their blood pressure (BP) levels, and whether or not they reached goal BP value. A multivariable logistical model was used to evaluate the risk factors of aTRH. The rate of antihypertensive treatment was 75.1%, BP control rate was 40.7%, and the prevalence of aTRH was 5.97% (169) according to the cross-sectional data among all the patients. The prevalence of aTRH patients taking 4 different classes of antihypertensive drugs or more was found to be 3.29% (93) in this study. Compared with non-aTRH patients, those with aTRH had a worse cardiovascular risk profile, including obesity (29.61% vs 20.53%, P = 0.005), hyperlipidemia (54.44% vs 46.66%, P = 0.050), type 2 diabetes mellitus (2-DM) (34.31% vs 25.64%, P = 0.013), and stroke (26.03% vs 19.26%, P = 0.032). After multivariable adjustment, logistic regression analyses showed that the risk factors of aTRH were male sex (OR 1.638; 95%CI 1.196–2.245, P = 0.002) and 2-DM (OR 1. 371; 95%CI 0.995–1.888, P = 0.049). Regular physical exercise (OR 0.696; 95%CI 0.505–0.960, P = 0.049) was a protective factor of aTRH. The prevalence of aTRH was 5.97% in older people in this cross-sectional study in China

MicroRNA-216a Promotes Endothelial Inflammation by Smad7/IκBα Pathway in Atherosclerosis

Background. The endothelium is the first line of defence against harmful microenvironment risks, and microRNAs (miRNAs) involved in vascular inflammation may be promising therapeutic targets to modulate atherosclerosis progression. In this study, we aimed to investigate the mechanism by which microRNA-216a (miR-216a) modulated inflammation activation of endothelial cells. Methods. A replicative senescence model of human umbilical vein endothelial cells (HUVECs) was established, and population-doubling levels (PDLs) were defined during passages. PDL8 HUVECs were transfected with miR-216a mimics/inhibitor or small interfering RNA (siRNA) of SMAD family member 7 (Smad7). Real-time PCR and Western blot assays were performed to detect the regulatory role of miR-216a on Smad7 and NF-κB inhibitor alpha (IκBα) expression. The effect of miR-216a on adhesive capability of HUVECs to THP-1 cells was examined. MiR-216a and Smad7 expression in vivo were measured using human carotid atherosclerotic plaques of the patients who underwent carotid endarterectomy (n=41). Results. Luciferase assays showed that Smad7 was a direct target of miR-216a. Smad7 mRNA expression, negatively correlated with miR-216a during endothelial aging, was downregulated in senescent PDL44 cells, compared with young PDL8 HUVECs. MiR-216a markedly increased endothelial inflammation and adhesive capability to monocytes in PDL8 cells by promoting the phosphorylation and degradation of IκBα and then activating NF-κB signalling pathway. The effect of miR-216a on endothelial cells was consistent with that blocked Smad7 by siRNAs. When inhibiting endogenous miR-216a, the Smad7/IκBα expression was rescued, which led to decreased endothelial inflammation and monocytes recruitment. In human carotid atherosclerotic plaques, Smad7 level was remarkably decreased in high miR-216a group compared with low miR-216a group. Moreover, miR-216a was negatively correlated with Smad7 and IκBα levels and positively correlated with interleukin 1 beta (IL1β) expression in vivo. Conclusion. In summary, our findings suggest a new mechanism of vascular endothelial inflammation involving Smad7/IκBα signalling pathway in atherosclerosis