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Background and Purpose: Intracranial arterial stenosis (ICAS) is a common cause of ischemic stroke in Asians, whereas whites tend to have more extracranial lesions. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been associated with ischemic stroke by a large amount of work. However, there are few studies focusing on the relationship of Lp-PLA2 and asymptomatic ICAS or extracranial arterial stenosis (ECAS). Wehereby sought to explore the relationship of Lp-PLA2 and ICAS, ECAS and concurrent stenosis in stroke-free hypertensive patients in Chinese population. Methods: All the subjects were evaluated for the presence and severity of ICAS and ECAS through computerized tomographic angiography (CTA) covered the whole brain down to the level of aortic arch. Lp-PLA2 mass was measured by enzyme linked immunoassay. The association of Lp-PLA2 and vascular stenosis was analyzed through multivariate logistic regression. Results: Among 414 participants, 163 (39.4%) had no ICAS or ECAS, 63 (15.2%) had ECAS only, 111 (26.8%) had ICAS only and 77 (18.6%) had concurrent extraintracranial stenosis. Lp-PLA2 mass was significantly associated with isolated ICAS (OR: 2.3; 95% CI: 1.14-4.64), and concurrent stenosis (OR: 3.93; 95% CI: 1.62-9.51), but was not related to isolated ECAS (OR: 1.54; 95% CI: 0.68-3.48). Lp-PLA2 mass was also associated with moderate to severe ICAS no matter how was the ECAS. Moreover, patients with higher Lp-PLA2 mass showed more sever ICAS and had more intracranial arterial lesions. Conclusion: This study revealed the association of Lp-PLA2 mass with ICAS in stroke-free hypertensive patients in Chinese population. The further long-term cohort study was warranted to elucidate the concrete effect of Lp-PLA2 on the asymptomatic ICAS. [ABSTRACT FROM AUTHOR]

Objectives: This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). Methods: The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d-1), arotinolol (30 mg·kg-1·d-1) for 8 weeks. Central arterial pressure (CAP) and pulse wave velocity (PWV) were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation (p-eNOS) of HAECs or aortas were analyzed by western blotting. Results: Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker). Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol. Conclusions: Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries. [ABSTRACT FROM AUTHOR]

Background: Most studies have suggested that elevated body mass index (BMI) was associated with the risk of death from all cause and from specific causes. However, there was little evidence illustrating the effect of BMI on the mortality in elderly hypertensive patients in Chinese population. Methods: The information of 10,957 hypertensive patients at baseline not less than 60 years were from Xinzhuang, a town in Minhang district of Shanghai, was extracted from the Electronic Health Record (EHR) system. All study participants were divided into eight categories of baseline BMI (with cut-points at 18, 20, 22, 24, 26, 28 and 30 kg/m2). Relative hazard ratio of death from all cause, cardiovascular and non-cardiovascular cause by baseline BMI groups were calculated, standardized for sex, age, smoking, drinking, physical activity, systolic blood pressure, history of cardiovascular disorders, serum lipid disturbance, diabetes mellitus and antihypertensive drug treatment. Results: During follow up (median: 3.7 years), 561 deaths occurred. Underweight (BMI<18 kg/m2) was associated with significantly increased mortality from all cause mortality (OR: 2.00; 95% CI: 1.43–2.79) and non cardiovascular mortality (OR: 2.76; 95% CI: 1.87–4.07), but not with cardiovascular mortality. For the cause specific analysis, the underweight was associated significantly with neoplasms (OR: 2.15; 95% CI: 1.16–4.00) and respiratory disorders (OR: 3.41; 95% CI: 1.64–7.06). The results for total mortality and specific cause mortality were not influenced by sex, age and smoking status. Conclusion: Our study revealed an association between underweight and increased mortality from non-cardiovascular disorders in elderly hypertensive patients in Chinese community. Overweight and obesity were not associated with all cause or cause specific death. [ABSTRACT FROM AUTHOR]

Background: Considerable efforts have been devoted to evaluating the association of the receptor for advanced glycation end-products (gene AGER and protein: RAGE) genetic variants to coronary artery disease (CAD); the results, however, are often irreproducible. To generate more information, we sought to explore four common polymorphisms of AGER and its circulating forms associated with the risk of CAD via a meta-analysis. Methodology/Principal Findings: Articles were identified by searching PubMed, EMBASE, Wanfang and CNKI databases before March 2013. Qualified articles had case-control designs and investigated AGER four polymorphisms (T-429C, T-374A, Gly82Ser, G1704A) or circulating soluble RAGE (sRAGE) or endogenous secretory RAGE (esRAGE) levels associated with CAD. Twenty-seven articles involving 39 independent groups fulfilled the predefined criteria. Overall, no significance was observed for all examined polymorphisms under allelic and dominant models. When restricting groups to CAD patients with diabetes mellitus or renal disease, deviations of risk estimates from the unity were stronger than overall estimates for all polymorphisms except for G1704A due to limited available studies. For example, under dominant model, having -429C allele increased the odds of developing CAD in diabetic patients by 1.22-fold (95% confidence interval (95% CI) 0.99–1.51; P = 0.06; I2 = 6.7%) compared with that of overall estimate of 1.15-fold (95% CI: 0.97–1.36; P = 0.111; I2 = 18.0%). Circulating sRAGE levels were non-significantly lower in CAD patients than in controls, whereas this reduction was totally and significantly reversed in CAD patients with diabetes mellitus (weighted mean difference: 185.71 pg/ml; 95% CI: 106.82 to 264.61 pg/ml). Circulating esRAGE levels were remarkably lower in CAD patients, as well as in subgroups with or without diabetes mellitus and without renal disease. Conclusions: Our findings demonstrated that association of AGER genetic polymorphisms with CAD was potentiated in patients with diabetes mellitus or renal disease. Practically, circulating esRAGE might be a powerful negative predictor for the development of CAD. [ABSTRACT FROM AUTHOR]

Background: KCNH2 (hERG) potassium channels have an integral role in regulating the excitability of smooth muscle cells. Some pathways driven by angiotensin II, nitric oxide and adrenergic receptors blocker are involved in modulating the properties of KCNH2 potassium channels. And these pathways are closely related to blood pressure regulation. Therefore, we hypothesized that KCNH2 genetic polymorphisms may affect blood pressure response to the antihypertensive drug therapies. Materials and Methods: To evaluate the interactions between KCNH2 genetic polymorphisms and individual blood pressure response to antihypertensive drugs, 370 subjects with essential hypertension (EH) were studied. In evaluating the interactions between KCNH2 genetic polymorphisms and drug response to blood pressure, multivariable ANOVA analysis followed by Bonferroni correction were carried out. Results: There were statistically significant interactions between KCNH2 (1956, C>T) polymorphism and DBP change (P = 0.010), MAP change (P = 0.014) on azelnidipine or nitrendipine therapy patients at the end of 6 weeks. We found that the KCNH2 (1956,C>T) polymorphism was associated with the hypotensive effects of α,β-ADR blockers of DBP change at the end of 4 and 6 weeks' treatment in an age- and gender-dependent manner (P = 0.007 and 0.019, respectively). Similar results were also observed for changes in MAP at the end of 4 and 6 weeks (P-values were 0.035 and 0.078, respectively). While patients who received imidapril, candesartan and irbesartan therapy, no significant difference in drug response among KCNH2(1956,C>T) genotype was observed. Conclusion: We have reported for the first time that KCNH2 (1956, C>T) polymorphism is associated with efficacy of antihypertensive drugs CCBs and ADR blockers, and may serve as a novel biomarker for individualized therapy for certain antihypertensive drugs. [ABSTRACT FROM AUTHOR]