Chinese Essential Hypertensive Patients Research Articles

Associations of methylenetetrahydrofolate reductase C677T genotype with blood pressure levels in Chinese population with essential hypertension

ABSTRACTObjective: To confirm the association between baseline blood pressure (BP) levels and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in patients with essential hypertension. Methods: A total of 347 patients were enrolled from the Dongzhi community in Anhui Province, China. The C677T polymorphism of the MTHFR gene was detected using high-throughput TaqMan allelic discrimination assay. Baseline BP was measured using a standardized mercury-gravity monometer. Results: In the whole sample, the frequency of the MTHFR C677T genotypes CC, CT, and TT were 38.6%, 48.1%, and 13.3%, respectively. In a recessive model (CC+CT versus TT genotypes), baseline diastolic blood pressure (DBP) was significantly higher in patients with the TT genotype compared to those with the CT or CC genotypes (P= 0.013). We also divided all patients into three groups based on the tertiles of the baseline BP distribution. Compared to subjects in the lowest tertile of DBP, the adjusted odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI: 1.1 to 6.2). However, no significant associations were observed between baseline systolic blood pressure (SBP) and the MTHFR C677T polymorphism. Conclusions: The MTHFR gene polymorphism could be an important genetic determinant of baseline DBP levels in Chinese essential hypertensive patients.

Influence of PRKCH gene polymorphism on antihypertensive response to amlodipine and telmisartan

ABSTRACTThis study aimed to evaluate the effect of PRKCH rs2230500 genetic polymorphism on efficacy of amlodipine and telmisartan for patients with hypertension. A total of 136 essential hypertension (EH) patients were treated with amlodipine (70 patients) or telmisartan (66 patients), respectively. Genetic polymorphism was genotyped by Sanger sequencing. Both baseline and post-treatment blood pressure (BP) and heart rate were measured to evaluate the influence of genetic polymorphism on the antihypertensive response. No significant difference in the absolute decrease in diastolic blood pressure (DBP),systolic blood pressure (SBP), and mean arterial pressure (MAP) was observed among PRKCH rs2230500 genotypes after 4-week amlodipine or telmisartan therapy (p > 0.05). However, when compared with carriers or GG genotype, the antihypertensive effect of PRKCH rs2230500 GA/AA carriers was superior in telmisartan treatment group. PRKCH rs2230500 gene polymorphism is significantly related to the efficiency in telmisartan therapy (p = 0.02). The PRKCH rs2230500 may influence the antihypertensive efficacy of telmisartan in Chinese EH patients, and further studies are needed to confirm these findings.

Leptin is associated with heart rate recovery in Chinese hypertensive patients

ABSTRACTElevated serum leptin concentrations are closely related to sympathetic nervous system activation in essential hypertension (EH); however, it is not clear whether or not they are associated with parasympathetic nervous system impairment in EH. Heart rate recovery (HRR) is a reproducible method used to assess parasympathetic activity. This study aimed to investigate the relationship between serum leptin and HRR in Chinese untreated EH patients. This was a cross-sectional study enrolling 471 Chinese EH patients (205 men, 266 women; mean age 63.1 years). HRR was calculated during an incremental cardiopulmonary exercise test. Simple and multiple regression analyses were used to assess the correlation between serum leptin level and HRR value. Serum leptin levels elevated with increasing BP values. Moreover, univariate analysis revealed that the HRR value was negatively correlated with serum leptin (r = −0.037, P < 0.01). In multiple regression analysis, the age-adjusted serum leptin level was negatively correlated with HRR (β = −0.268, P < 0.01). Serum leptin remained negatively associated with HRR (β = −0.017, P < 0.01) after further adjustments for factors including age, systolic blood pressure, total cholesterol, and several factors that correlated with HRR. Our findings demonstrated that a raised serum leptin concentration is related to HRR blunt, which suggests that the role of leptin in the development of EH might be associated with impairment of the parasympathetic nervous system as well.

Positive association between KCNJ5 rs2604204 (A/C) polymorphism and plasma aldosterone levels, but also plasma renin and angiotensin I and II levels, in newly diagnosed hypertensive Chinese: a case-control study.

Variants in G protein-coupled inward rectifier K+ channels 4 (GIRK4 also known as KCNJ5) gene are associated with primary aldosteronism, which is the most common cause of secondary hypertension. The KCNJ5 rs2604204 variant was shown to be common (minor allele frequency=32.5%) in Chinese patients with essential hypertension (EH). The relationship between KCNJ5 variant and plasma aldosterone (ALD) levels in EH patients has not been reported. We collected 229 patients with newly diagnosed EH without any antihypertensive agents. According to the median standing plasma ALD, high-ALD and control groups were divided. Clinical data and blood samples were collected. KCNJ5 rs2604204 genotype was determined by PCR. The results showed that the levels of triglyceride, uric acid, insulin, insulin resistance (IR) index, renin, angiotensin I (Ang I), angiotensin II (Ang II), cortisol, 24 h mean systolic blood pressure (SBP) and daytime mean SBP were significantly increased in the high-ALD group than those in the control group, as well as 24 h s.d. of SBP and diastolic BP (DBP), and 24 h coefficient of variance of SBP and DBP. Notably, the distribution frequency of AC and CC genotypes, and the C allele of KCNJ5 were also significantly higher in the high-ALD group. Logistic regression analysis showed that the C allele of KCNJ5 rs2604204 was one risk factor for increased plasma ALD in Chinese EH patients (P=0.008, odds ratio=2.2 (95% confidence interval 1.2-4.1)). Our findings indicated that the variation of plasma ALD might be associated with increased IR and BP variability. Moreover, KCNJ5 rs2604204 polymorphism was related to increased plasma ALD level, but also plasma renin, Ang I and II levels in newly diagnosed, never-treated EH patients.

Influence of G-protein β-Polypeptide 3 C825T Polymorphism on Antihypertensive Response to Telmisartan and Amlodipine in Chinese Patients.

Background:G-protein β-polypeptide 3 (GNB3) is a β subunit isoform of G-protein that plays important role in signal transduction of membrane G-protein coupled receptors (GPCRs). The GNB3 splice variant C825T (rs5443) is associated with risk for essential hypertension (EH) and efficacy of therapeutic drugs targeting GPCRs. It is unknown whether the polymorphism is associated with blood pressure (BP) response to telmisartan or amlodipine, two widely prescribed antihypertensive drugs.Methods:A total of 93 subjects initially diagnosed as EH were recruited and underwent a 4-week treatment with telmisartan (42 patients) or amlodipine (51 patients) monotherapy. Both baseline and after-treatment BP were measured. GNB3 C825T polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism.Results:Baseline systolic BP (SBP) and diastolic BP (DBP) were comparable among C825T genotypes in both telmisartan and amlodipine treatment groups. Patients with the CT or TT genotypes showed significantly lower body mass index (BMI) as compared with CC homozygotes in both groups (P < 0.05, respectively). GNB3 825TT homozygotes showed significantly higher after-treatment DBP and mean arterial pressure (MAP) than those carrying at least one 825C allele (P < 0.01) in the telmisartan treatment group. No difference in after-treatment SBP, DBP, and MAP levels among C825T genotypes was observed in the amlodipine treatment group. No significant difference in absolute changes in BP levels was observed among the genotypes in either treatment group.Conclusion:The GNB3 C825T splice variant is associated with the DBP-lowering effect of telmisartan but not amlodipine in Chinese EH patients.

Relationship between eNOS 894G&amp;gt;T Polymorphism and the Antihypertensive Efficiency of Two Dihydropyridine Calcium Channel Blocker Drugs, Azelnidipine and Nitrendipine, in Chinese EH Patients

Background: Dihydropyridine calcium-channel blockers (dCCBs) were widely used in anithypertensive treatment. The aim of this study was to examine the effect of polymorphisms of CACNA1C, eNOS and RGS2 on the antihypertensive efficiency of dihydropyridine calcium channel blocks (dCCBs) in Chinese patients with essential hypertension (EH). Methods: A total of 107 untreated Chinese mild to moderate EH patients were enrolled in this study, and had been prescribed azelnidipine or nitrendipine as monotherapy. All patients who had gave informed consent for genetic research were divided into two groups: treated with azelnidipine or nitrendipine for at leaset 6 weeks. Five polymorphisms of three blood pressure (BP) and hypertension susceptible genes were studied in our research, and these polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Every patients’ BP and heart rate were measured at 0 week, 2 weeks, 4 weeks and 6 weeks. The biochemical parameters of blood were detected before and 6 weeks after the administration. Adverse effects were evaluated at the last visitation. Results: Both the systolic and diastolic BP levels were significanlty decreased after six weeks of dCCBs treatment, from 149.3 ± 9.2 mmHg to 132.2 ± 11.7 mmHg and form 97.9 ± 3.0 mmHg to 85.5 ± 7.5 mmHg, as well as the levels of TP, TBIL, CHO and LDL, the P-values were P=0.017, P=0.045, P=0.039, P=0.041 respectivley. As 11 of 75 patients appeared adverse reactions, the rate of adverse effects showed no difference in various genotypes. There were significant interactions between eNOS G894T polymorphism and △DBP, △MBP on azelnidipine therapy patients, but not in nitrendipine, the GG genotype carriers were more sensitive in blood decrease than GT/TT genotype carriers (P<0.05). Conclusion: CCBs had potential hepatoprotective and antiatheroscloresis effects for Chinese EH paitents. And the eNOS G894T polymorphism is associated with the hypotensive effect of azelnidipine.

The efficacy and safety of fixed-dose combination of amlodipine/benazepril in Chinese essential hypertensive patients not adequately controlled with benazepril monotherapy: a multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial

This double-blind, double-dummy clinical trial evaluated the efficacy and safety of two strengths of fixed-dose combination of amlodipine/benazepril in Chinese hypertensive patients not adequately controlled with benazepril. Of 442 patients who received treatment with benazepril 10 mg for 4 weeks, 341 patients failed to achieve to diastolic blood pressure (DBP) <90 mmHg. These non-responders were randomized to receive amlodipine/benazepril 2.5/10 mg, or amlodipine/benazepril 5/10 mg, or benazepril 10 mg for 8 weeks. BP reductions with amodipinel/benazepril 2.5/10 mg (15.2/11.8 mmHg) or amlodipine/benazepril 5/10 mg (15.4/12.4 mmHg) were significantly greater than that with benazepril 10 mg (9.88/9.46 mmHg) at study end (p < 0.01, combination versus benazepril). BP control rate was 83.8% with amlodipine/benazepril 2.5/10 mg, 80.2% with amlodipine/benazepril 5/10 mg, 64.9% with benazepril 10 mg at study end (p < 0.01, combination versus benazepril). Three groups were generally well tolerated. Our study indicated that amlodipine/benazepril fixed-dose combination offered significant additional BP reductions and BP control rate compared with the continuation of benazepril monotherapy. No significant differences were observed in both BP reductions and BP control rate between amlodipine/benazepril 2.5/10 mg and amlodipine/benazepril 5/10 mg.

Racial difference in aldose reductase C-106T genetic polymorphism and association with essential hypertension.

To investigate the distribution of aldose reductase (AR) C-106T genetic polymorphism in Chinese Han population and its association with the risk for essential hypertension (EH). The AR C-106T polymorphism was genotyped in 148 Chinese EH patients and 137 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotype distribution between groups was contrasted by Χ(2)- test and the degree of genetic association was evaluated by 95% confidence interval (CI). Frequency of the variant AR C-106T allele was 13.9% (95% CI: 11.2%-16.6%) in the controls, which was significantly lower than that in the Japanese (18.4% in 712 individuals, P=0.0063), the Australians (37.9% in 240 individuals, P<0.0001) and the Brazilians (34.7% in 62 individuals, P<0.0001). The frequency of AR C-106T allele was 11.7% (95% CI: 7.9%-15.5%) in the EH patients. No significant difference in the allele frequency was observed between the EH patients and the controls (P=0.147). There is obvious racial difference in the distribution of AR C-106T polymorphism. The polymorphism is not associated with the risk for EH.

Metabolic syndrome and risk of atrial fibrillation in Chinese essential hypertensive patients

Objective: Metabolic syndrome (MS) has been associated with a high prevalence of atrial fibrillation (AF) in a community based population. However, there is little data regarding the association between MS and risk of atrial fibrillation (AF) in essential hypertensive (EH) patients. Methods: This was a retrospective cross-sectional analysis of prospectively collected data in a total of 2782 hospitalized EH patients from 1995 to 2007 in China, which were divided into EH+non MS group (n=1761) and EH+MS group (n=1021) according to MS criteria.

Metabolic syndrome and risk of atrial fibrillation in Chinese essential hypertensive patients

Purpose: Metabolic syndrome (MS) has been associated with a high prevalence of atrial fibrillation (AF) in a community based population. However, there is little data regarding the association between MS...

Poor sleep quality, stress status, and sympathetic nervous system activation in nondipping hypertension

It has been reported that poor sleep quality is associated with nondipping hypertension, but the underlying mechanisms were not reported. This study was carried out to evaluate whether poor sleep quality is associated with stress status and sympathetic nervous system activation in nondippers. A total of 307 Chinese essential hypertensive patients were defined as dippers or nondippers by ambulatory blood pressure monitoring. Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI), and stress status was assessed by Perceived Stress Scale (PSS). The levels of epinephrine and norepinephrine were examined to investigate the underlying mechanisms. A total of 204 (66.4%) and 103 cases (33.6%) were found to be dippers and nondippers, respectively. Nondippers were with poorer sleep quality (P<0.05), more stressful status (P<0.05), and with an increased activity of sympathetic nervous system (P<0.01). The decline of systolic BP (SBP) and diastolic BP (DBP) at night was inversely related with the PSQI score (r=-0.469, P<0.01 and r=-0.421, P<0.01), PSS score (r=-0.432, P<0.01 and r=-0.404, P<0.01), epinephrine (r=-0.304, P<0.05 and r=-0.293, P<0.05), and norepinephrine (r=-0.321, P<0.05 and r=-0.357, P<0.05). Multiple logistic regression analyses showed that older age [odds ratio (OR): 1.69; 95% confidence interval (CI): 1.22-2.43], PSQI score (OR: 2.78; 95% CI: 1.65-6.87), and PSS score (OR: 2.43; 95% CI: 1.56-5.93) were independently correlated with the nondipping pattern. Poor sleep quality and stressful status were closely associated with higher activation of sympathetic nervous system, and they are independent predictors of nondipping hypertension.

G501C polymorphism of the oxidized LDL receptor gene is associated with albuminuria in Chinese essential hypertension patients.

Albuminuria is an independent predictor of renal and cardiovascular complications in hypertensive subjects. We previously showed that lectin-like oxidized low density lipoprotein receptor 1 (OLR-1) polymorphisms at G501C are associated with susceptibility to essential hypertension and serum C-reactive protein levels. We have now investigated a possible association between OLR-1 polymorphisms at G501C, genotyped by PCR-RFLP, and severity of albuminuria in 307 hypertensive Chinese subjects and 225 age- and sex-matched controls. Urine albumin concentration /urine creatinine concentrations (ACR) were measured to evaluate the severity of albuminuria. Hypertensive subjects had a significantly higher frequency of the CC genotype and the C allele of the OLR-1 polymorphism than controls; this was also true for . hypertensive subjects with macroalbuinuria and microalbuminuria compared to those with normoalbuminuria. The mean ACR levels and mean serum C-reactive protein levels in CC carriers were significantly higher than in GG and GC carriers. There was a significant, positive correlation between serum hs-C-reactive protein levels and ACR levels. We conclude that OLR-1 polymorphisms at G501C affect the severity of albuminuria in essential hypertension patients.

G501C polymorphism of the oxidized LDL receptor gene is associated with albuminuria in Chinese essential hypertension patients

G501C polymorphism of the oxidized LDL receptor gene is associated with albuminuria in Chinese essential hypertension patients

Azelnidipine and Amlodipine: A Comparison of Their Effects and Safety in a Randomized Double-Blinded Clinical Trial in Chinese Essential Hypertensive Patients

The purpose of this study is to compare the effects and safety of azelnidipine and amlodipine in Chinese essential hypertensive patients. Patients were randomized to receive administration of azelnidipine 8–16 mg/day or amlodipine 2.5–5 mg/day for 8 weeks. The blood pressure and pulse rate were evaluated in an outpatient clinic and by ambulatory blood pressure monitoring. There were 220 patients enrolled to the study. The blood pressure in both groups was decreased significantly (P < 0.001). Compared with amlodipine, the patients received azelnidipine had better response in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (P < 0.01). No significant changes of pulse rate were observed in either group. For the ambulatory blood pressure monitoring, both drugs had stable anti-hypertensive effects over 24 h. The trough/peak ratios of DBP for the azelnidipine and amlodipine groups were, respectively, 46% and 40%. Adverse events occurred at 7.3% and 10.0%, respectively in the azelnidipine and amlodipine groups (P = 0.485). Headache and dizziness were observed at an incidence of more than 1% in both groups. Once-daily administration of azelnidipine effectively controlled blood pressure and had a stable action over 24 h. Azelnidipine had good safety and compliance similar to amlodipine.

A Common Haplotype on Methylenetetrahydrofolate Reductase Gene Modifies the Effect of Angiotensin-Converting Enzyme Inhibitor on Blood Pressure in Essential Hypertension Patients—A Family-Based Association Study

Our recent study indicated that MTHFR C677T polymorphism may involve in genetic control of blood pressure response to treatment by benazepril, an ACE inhibitor. Currently, we proposed to further investigate whether short-term blood pressure response to benazepril, was modulated by haplotypes re-constructed from both C677T and A1298C polymorphisms in MTHFR gene. A total of 410 hypertensive patients recruited from 344 nuclear families were treated orally with benazepril at a daily dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. In addition, 689 family members of these patients were also genotyped. Among these patients, the frequency of MTHFR A1298C AA, AC and CC genotypes was 74.4%, 23.9%, and 1.7%, respectively. The frequency of MTHFR C677T CC, CT and TT genotypes was 23.7%, 51.2%, and 25.1%, respectively. Only three haplotypes, 677T-1298A (50.8%), 677C-1298A (35.7%), and 677C-1298C (13.5%) were re-constructed. Multivariate regression models with generalized estimating equation (GEE) correction detected that the individuals carrying one copy of haplotype 677C-1298C had significantly lower diastolic and systolic blood pressure response (ΔDBP and ΔSBP) to benazepril treatment (p= 0.003 and p =0.043, respectively), in comparison to those without haplotype 677C-1298C. The results of family-based association test further confirmed that haplotype 677C-1298C was more frequently transmitted in subjects with either lower residual of ΔDBP or ΔSBP. For residual of ΔDBP, the p-values are 0.007 in an additive model and 0.005 in a dominant model. For residual of ΔSBP, the p-values are 0.009 in an additive model and 0.006 in a dominant model. Our findings suggest that MTHFR 677C-1298C haplotype modulate blood pressure responsiveness to shortterm treatment of ACE inhibitor in Chinese essential hypertensive patients.

The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with the level of decrease on diastolic blood pressure in essential hypertension patients treated by angiotensin-converting enzyme inhibitor

Objectives: Elevated plasma homocysteine has been implicated as a risk factor for hypertension. C677T polymorphism in methylenetetrahydrofolate reductase gene ( MTHFR) is a major determinant of hyperhomocysteinemia, which results in endothelial dysfunction. Angiotensin-converting enzyme (ACE) inhibitors appear to remedy the endothelial dysfunction and restore endothelium-dependent vasodilatation. The co-existence of genetic polymorphisms in drug metabolizing enzymes, targets, receptors, and transporters may influence the drug efficacy. The purpose of this study was to investigate whether short-term blood pressure control by benazepril, an ACE inhibitor, was modulated by C677T MTHFR gene polymorphism. Methods and results: A total of 444 hypertensive patients, aged 27 to 65 years, without any anti hypertensive therapy within 2 weeks were included. All of them were treated orally with benazepril at a single daily fixed dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. Among them, the frequency of MTHFR C677T genotype CC, CT and TT was 24.3%, 51.8%, and 23.9%, respectively. In a recessive model ( CC+ CT versus TT genotype), both baseline diastolic blood pressure (DBP) and diastolic blood pressure response (ΔDBP) were significantly higher in patients with the TT genotype than in those with the CT or CC genotype ( P value=0.0076 for DBP, and P value=0.0005 for ΔDBP). We further divided all patients into three groups based on the tertiles of the ΔBP distribution. Compared to subjects in the lowest tertile of ΔDBP, the adjusted relative odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI, 1.4 to 4.9). However, baseline systolic blood pressure (SBP) and SBP response did not significantly associate with MTHFR C677T polymorphism. Conclusions: Our finding suggests that MTHFR C667T polymorphism modulated baseline DBP and DBP responsiveness by short-term treatment of ACE inhibitor in Chinese essential hypertensive patients.