Genetic basis of index patients with familial hypercholesterolemia in Chinese population: mutation spectrum and genotype-phenotype correlation.

BACKGROUND: Although there have been many reports in the genetics of familial hypercholesterolemia (FH) worldwide, studies in regard of Chinese population are lacking. In this multi-center study, we aim to characterize the genetic spectrum of FH in Chinese population, and examine the genotype-phenotype correlations in detail. METHODS: A total of 285 unrelated index cases from China with clinical FH were consecutively recruited. Next-generation sequencing and bioinformatics tools were used for mutation detection of LDLR, APOB and PCSK9 genes and genetic analysis. RESULTS: Overall, the detection rate is 51.9% (148/285) in the unrelated index cases with a total of 119 risk variants identified including 84 in the LDLR gene, 31 in APOB and 4 in PCSK9 gene. Twenty-eight variants were found in more than one individual and LDLR c.1448G > A (p. W483X) was most frequent one detected in 9 patients. Besides, we found 8 (7 LDLR and 1 APOB) novel variants referred as "pathogenic (or likely pathogenic) variants" according to in silico analysis. In the phenotype analysis, patients with LDLR null mutation had significantly higher LDL cholesterol level than LDLR defective and APOB/PCSK9 mutation carriers and those with no mutations (p < 0.001). Furthermore, 13 double heterozygotes, 16 compound heterozygotes and 5 true LDLR homozygotes were identified and the true LDLR homozygotes had the most severe phenotypes. CONCLUSIONS: The present study confirmed the heterogeneity of FH genetics in the largest Chinese cohort, which could replenish the knowledge of mutation spectrum and contribute to early screening and disease management.

Rs495828 polymorphism of the ABO gene is a predictor of enalapril-induced cough in Chinese patients with essential hypertension.

OBJECTIVE: ABO genetic polymorphisms have recently been associated with angiotensin-converting enzyme (ACE) activity and inflammation, which play a critical role in the pathogenic mechanism of ACE inhibitor-induced cough. Therefore, the current study determined the association of ABO genetic polymorphisms with enalapril-induced cough in Chinese patients with essential hypertension. METHODS: A total of 450 essential hypertensive patients treated with 10 mg of enalapril maleate were genotyped for ABO genetic polymorphisms using the PCR-direct sequencing method. Cough was recorded when patients were bothered by cough and respiratory symptoms during enalapril treatment without an identifiable cause. RESULTS: The distribution of rs8176740 and rs495828 was different between the coughers and the controls [P=0.039; odds ratio (OR)=0.70, P=0.018; OR=1.41]. The risk of enalapril-induced cough in the rs495828 TT carriers was increased (P=0.008; OR=2.69), which remained significant after false discovery rate correction. The results for the rs8176740 polymorphism were significant in the female subgroup (P=0.027; OR=0.22). Haplotype analysis of the four ABO polymorphisms (rs8176746/rs8176740/rs495828/rs12683493) showed that the frequency of the GATC haplotype was higher in the coughers than those in the controls (26.6 vs. 18.8%, P=0.033; OR=1.43). CONCLUSION: The rs495828 polymorphism was associated with enalapril-induced cough and may serve as a useful pharmacogenomics marker of the safety of enalapril in Chinese patients with essential hypertension. The mechanism for the associations may involve the effects of the ABO gene or ABO blood type on ACE activity and inflammation.

Hyperhomocysteinemia accelerates collagen accumulation in the adventitia of balloon-injured rat carotid arteries via angiotensin II type 1 receptor.

Recent studies suggest that hyperhomocysteinemia (HHcy) increases collagen type I accumulation in rat vascular adventitia after balloon injury and that Angiotensin II (Ang II) induces collagen synthesis in vascular adventitial fibroblasts. Reports also indicate that Ang II type1 receptor (AT1R) activation, mediated by homocysteine (Hcy) may contribute to collagen type 1 expression in mouse aortic endothelial cells. However, little is known about the possible mechanisms behind the relationship between Hcy and AT1R in adventitial remodeling. Thus, we investigated whether HHcy induces collagen accumulation via activation of AT1R in the adventitia. Male Sprague-Dawley (SD) rats were randomly divided into a control group and a 1% l-methionine-induced HHcy group. Balloon injury was performed after 12 experimental weeks and animals were sacrificed at 7, 14, and 28 days after injury. Collagen deposition and AT1R expression was measured with Western blot. Serum Hcy, adventitial collagen, and AT1R levels were higher in the HHcy group compared with the control group. Hcy time-dependently induced collagen type 1 and AT1R expression, with the highest induction observed at 48 h. Also, we observed that the AT1R blocker, valsartan, attenuated collagen type 1 and AT1R expression. HHcy exacerbates adventitial remodeling after balloon injury, and the underling mechanisms may be related to AT1R activity.

[Blood pressure control and glucose metabolism status in hypertension specialty clinics in China].

OBJECTIVE: To investigate blood pressure control the glucose metabolism, cardiovascular risk factors of patients who were regularly followed up at professional hypertension clinics in China. METHODS: A cross-sectional survey was conducted in 32 004 patients from 127 professional hypertension clinics across China. The questionnaires included case history and related treatment physical examination and laboratory biochemical tests were also taken at the same time. RESULTS: The mean blood pressure of overall population was (151 ± 13)/(92 ± 10) mm Hg(1 mm Hg = 0.133 kPa). Totally 3424 patients (10.7%) had never taken any anti-hypertension medicine. Among patients treated with anti-hypertension drugs, 19 818 were of mono-therapy (69.3%) and 8762 were of combination therapy. The most frequently used drug was renin-angiotensin system inhibitor, followed by calcium-channel blocker. Fixed compound preparations accounted for 15.6%. The overall blood pressure control rate (<140/90 mm Hg ) was 26.8%, among them, 27.7%, 30.0%, 25.4% and 21.3% patients were complicated with coronary heart disease, diabetes mellitus, kidney diseases and cerebral stroke respectively. About 70.3% hypertensive patients had abnormal glucose metabolism whose mean glycosylated hemoglobin (GHbA1c) was 7.84%, which was significantly higher than 7.0% , the target value defined by ADA.Even among them, 20.2% patients have never received any anti-diabetic drugs.Low-risk and medium-risk patients accounted for 16.0%. Totally 48.0% patients were classified in high-risk group and 36.0% in very high risk group. About half of all patients had different target organ dysfunction. About 49.0% patients had associated comorbidities. CONCLUSIONS: Co-existence of hypertension and abnormal glucose metabolism is common in Chinese population. Among these patients, target organ dysfunction and comorbidities are prevalent, but blood pressure is only effectively controlled in less than 30% patients. Low proportion of combination therapy is one of the reasons for unsatisfied control of blood pressure.It indicates that effective management of hypertension is urgent.

[Characteristics and related risk factors of arterial elasticity in prehypertensive persons].

OBJECTIVE: To explore the characteristics and related risk factors of arterial elasticity in persons with prehypertension, high-normal blood lipid and(or) impaired glucose regulation(impaired fasting glucose and(or) impaired glucose tolerance). METHODS: After receiving physical and biochemical examinations, a total of 1238 persons were enrolled. Among them, the etiologies were prehypertension (n = 65), high-normal blood lipid (n = 156), impaired glucose regulation (n = 159), prehypertension and high-normal blood lipid (n = 85), prehypertension and impaired glucose regulation (n = 77), high-normal blood lipid and impaired glucose regulation (n = 55) and prehypertension, high-normal blood lipid and impaired glucose regulation (n = 9). Also 332 healthy subjects, 113 hypertensive patients, 150 hyperlipidemics and 37 diabetics were enrolled as controls. Systemic vascular compliance (SVC), systemic vascular resistance (SVR), brachial artery distensibility (BAD) were measured with Dynapulse 200 M (Pulse Metric, Inc., USA). RESULTS: In persons with prehypertension, SVC was lower than healty group ((1.14 ± 0.20) ml vs (1.26 ± 0.23) ml, P < 0.01)and higher than hypertensive group ((1.11 ± 0.18) ml, P = 0.011), SVR higher than healty group (157 ± 29) kPa×s×L(-1) vs (148 ± 25) kPa×s×L(-1), P = 0.012) and lower than hypertensive group ((166 ± 36) kPa×s×L(-1), P < 0.01)and BAD lower than healty group(5.93% ± 1.14% vs 6.50% ± 1.30%, P < 0.01). Among different groups with prehypertension, high-normal blood lipid and(or) impaired glucose regulation, SVC, SVR and BAD had significant differences. As indicated by multiple linear regression analysis, blood pressure was an independent risk factor of arterial elasticity. CONCLUSIONS: Vascular function becomes damaged in prehypertensive stage. As an independent risk factor, blood pressure had more potent effect than lipid and blood glucose. Multiple cardiovascular risk factors with high-normal value may affect vascular function more strongly.

[Effects of different antihypertensive strategies on reversing urinary albumin excretion].

OBJECTIVE: To explore the effects of different antihypertensive strategies on blood pressure and urinary albumin excretion in patients with hypertension and microalbuminuria. METHODS: For this multi-center, randomized, positively controlled clinical trial, a total of 531 patients with mild-to-moderate essential hypertension and microalbuminuria were enrolled. They were divided randomly into calcium channel blocker (CCB), angiotensin II receptor antagonist (ARB) and CCB+ARB groups. The whole treatment period was 6 months. RESULTS: According to ANOVA analysis, the post-therapeutic urinary albumin level decreased 20.6, 27.6 and 30.9 mg/L in CCB, ARB and CCB+ARB groups respectively (P = 0.067). And the extents of urinary albumin reduction were 31.1 and 6.6 mg/L in patients with controlled and uncontrolled blood pressure respectively (P < 0.001). CONCLUSION: Effective antihypertensive therapy is a key for decreasing urinary albumin excretion in hypertensive patients. As compared with calcium antagonists, ARB-containing regimens appear to be better in reducing urinary albumin.

[Status of glucose metabolism in Chinese essential hypertensive patients].

OBJECTIVE: To investigate glucose metabolism status and its relationship with blood pressure, obesity, renal function and cardio-cerebral vascular events in Chinese essential hypertensive patients. METHODS: Essential hypertensive patients without diabetic history were enrolled in this cross-sectional survey. All patients filled in questionnaires and received physical examination and laboratory tests. Oral glucose tolerance test (OGTT, fasting and 2 hours glucose level after drinking the 75 g glucose solution) was performed in patients who signed the informed consent. RESULTS: (1) The control rate of systolic BP was lower in patients with dysglycemia than in patients without dysglycemia (41.0% vs. 46.4%, P = 0.000). (2) The albuminuria detection rate and the abnormal rate of estimated glumerular filtration rate (eGFR) increased significantly with the deterioration of glucose metabolism. (3) Multifactor-analysis showed that abnormal waist circumference, decreased eGFR and presence of albuminuria were independent risk factors for abnormal glucose metabolism. Cardiovascular events was significantly higher in patients with abnormal glucose metabolism than patients with normal glucose metabolism. CONCLUSION: Abnormal glucose metabolism is common in Chinese essential hypertensive patients. When complicated with abnormal glucose metabolism, essential hypertensive patients had poor blood pressure control rate and were related to higher cardiovascular risk.

Efficacy and tolerability of a single-pill combination of amlodipine/valsartan in Asian hypertensive patients not adequately controlled with valsartan monotherapy.

This randomized, double-blind study evaluated efficacy of a single-pill combination of amlodipine/valsartan (Aml/Val) in Asian patients with hypertension not responding to Val 80 mg. Patients with mean sitting diastolic blood pressure (DBP) ≥90-≤110 mmHg were randomized to Aml/Val 5/80, Val 80, or Val 160 mg for 8 weeks. At week-8 endpoint, significantly greater reductions in BP were seen with Aml/Val 5/80 mg than valsartan monotherapies (p < 0.0001). The BP control was greater with Aml/Val 5/80 (70.5%) than Val (44.1-58.6%) monotherapies. The combination was well tolerated. In conclusion, single-pill combination with Aml/Val provided significant additional BP reduction and control in hypertensive patients not responding to Val 80 mg.

2019 Chinese Hypertension League guidelines on home blood pressure monitoring.

In China, automated blood pressure monitors have been readily available for home use. Home blood pressure monitoring has been indispensable in the management of hypertension. There is therefore a need to establish guidelines for home blood pressure monitoring on the basis of the 2012 consensus document. In this guidelines document, the committee put forward recommendations on the selection and calibration of blood pressure measuring devices, the frequency (times) and duration (days) of blood pressure measurement, and the diagnostic threshold of home blood pressure.

Calcineurin-NFAT signaling is involved in phenylephrine-induced vascular smooth muscle cell proliferation.

AIM: Catecholamine-induced vascular smooth muscle cell (VSMC) proliferation is one of the major events in the pathogenesis of atherosclerosis and vascular remodeling. The calcineurin-NFAT pathway plays a role in regulating growth and differentiation in various cell types. We investigated whether the calcineurin-NFAT pathway was involved in the regulation of phenylephrine-induced VSMC proliferation. METHODS: Proliferation of VSMC was measured using an MTT assay and cell counts. Localization of NFATc1 was detected by immunofluorescence staining. NFATc1-DNA binding was determined by EMSA and luciferase activity analyses. NFATc1 and calcineurin levels were assayed by immunoprecipitation. RESULTS: Phenylephrine (PE, an alpha(1)-adrenoceptor agonist) increased VSMC proliferation and cell number. Prazosin (an alpha(1)-adrenoceptor antagonist), cyclosporin A (CsA, an inhibitor of calcineurin) and chelerythrine (an inhibitor of PKC) decreased PE-induced proliferation and cell number. Additional treatment of VSMC with CsA or chelerythrine further inhibited proliferation and cell number in the chelerythrine-pretreatment group and the CsA-pretreatment group. CsA and chelerythrine alone had no effect on either absorbance or cell number. CsA decreased PE-induced calcineurin levels and activity. NFATc1 was translocated from the cytoplasm to the nucleus upon treatment with PE. This translocation was reversed by CsA. CsA decreased the PE-induced NFATc1 level in the nucleus. PE increased NFAT's DNA binding activity and NFAT-dependent reporter gene expression. CsA blocked these effects. CONCLUSION: CsA partially suppresses PE-induced VSMC proliferation by inhibiting calcineurin activity and NFATc1 nuclear translocation. The calcineurin-NFATc1 pathway is involved in the hyperplastic growth of VSMC induced by phenylephrine.

Distinctive effects of carvedilol in the non-infarct zone: remodelling of the ligated rat heart linked to oxidative stress.

In this study, an experimental rat ligated heart model was used to observe the effect of treatment with carvedilol, metoprolol and metoprolol plus a highly selective alpha(1)-adrenergic blocking agent, bunazosin, after acute myocardial infarction (MI). Compared with an untreated MI group, all drug-treated groups demonstrated attenuation of inflammatory mediators, activation of nuclear factor-kappaB (NF-kappaB), and increased levels of mRNA and active protein for the collagenases matrix metallopeptidase (MMP)-8 and MMP-13 in the non-infarct zone of the ventricle, as well as inhibition of the increase of left ventricular end-diastolic pressure. Supplementation of metoprolol with bunazosin did not add greatly to the effects of metoprolol alone. Of the three drug treatments, carvedilol showed a uniquely potent antioxidant activity that may strengthen its capacity to inhibit oxidative stress, the release of inflammatory mediators and activation of NF-kappaB. This study may help provide a mechanistic explanation for the greater benefits shown by carvedilol compared with metoprolol in treating heart failure.

Endogenous hydrogen sulfide and ERK1/2-STAT3 signaling pathway may participate in the association between homocysteine and hypertension.

BACKGROUND: Homocysteine (Hcy) is a risk factor for hypertension, although the mechanisms are poorly understood. METHODS: We first explored the relationship between Hcy levels and blood pressure (BP) by analyzing the clinical data of primary hypertensive patients admitted to our hospital. Secondly, we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S. An hyperhomocysteinemia (HHcy) rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism. We carried out tissue histology, extraction and examination of RNA and protein. Finally, we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system (RAAS) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. RESULTS: In primary hypertensive inpatients with HHcy, blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy. In the rat model, blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment. Angiotensin converting enzyme 1 (ACE1) expression in the Wistar Hcy group was enhanced comparing to controls, but was decreased in the Wistar folate group. Angiotensin II receptor type 1 (AGTR1) levels in the kidney tissue increased in the Wistar folate group. Both serum H2S and kidney cystathionine γ-lyase decreased with elevated levels of serum Hcy. In vitro, increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1. This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression. CONCLUSION: Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels, in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.

Protective effects of dehydrocavidine on carbon tetrachloride-induced acute hepatotoxicity in rats.

AIM OF THE STUDY: To investigate the protective effects of dehydrocavidine (DC), a main active ingredient of Corydalis saxicola Bunting (Yanhuanglian), on carbon tetrachloride (CCl4)-induced hepatotoxicity and the possible mechanisms involved in male Sprague-Dawley rats. MATERIALS AND METHODS: Acute hepatotoxicity was induced by CCl4 intoxication in rats. Serum biological analysis, lipid peroxides and antioxidants estimation, histopathological studies were carried out. RESULTS: Both pre-treatment with DC prior to CCl4 administration and post-treatment with DC after CCl4 administration significantly prevented increases in serum enzymatic activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and total bilirubin (TBIL). In addition, pre- and post-treatment with DC also significantly prevented formation of hepatic malondialdehyde (MDA), depletion of glutathione peroxidase (GPx) and depression of superoxide dismutase (SOD) in the liver of CCl4-intoxicated rats. ALT, AST, LDH, ALP and TBILL levels, as well as MDA, SOD and GPx activities were unaffected in normal rats by treatment with DC alone. GST, a phase II enzyme, had no significant changes during our experiments. Histopathological changes induced by CCl4 were also significantly attenuated by DC treatment in both preventive and curative experiments. CONCLUSIONS: DC has a potent hepatoprotective effect on CCl4-induced liver injury in rats through its antioxidant activity.

[Curative effects on mild to moderate primary hypertension and influence on pulse wave velocity of slow releasing felodipine].

OBJECTIVE: To evaluate the curative effects of slow releasing felodipine on mild to moderate primary hypertension and its influence on the pulse wave velocity of slow of the patients. METHODS: 260 patients with mild to moderate primary hypertension, aged 35-79, received slow releasing felodipine with the initial dosage of 5 mg once daily for 2 weeks. By the end of the second week, 222 of the 260 patients with their blood pressure (BP) levels<140/90 mm Hg were treated by the same regimen for 12 weeks. Pulse wave velocity (PWV) was measured before the treatment, and by the ends of the second and fourteenth weeks. Intention to treat analysis (ITT analysis) was adopted. RESULTS: After 2-week treatment the systolic BP decreased by 21.4 mm Hg and diastolic BP by 14.2 mm Hg (both P<0.01). After 14-week treatment, the BP decreased by 24.8/17.5 mm Hg (P<0.01), the systolic BP decreased by 16.5% and the diastolic BP decreased by 18.4%. The BP of the patients with their BP levels up to standard decreased by 22.8/15.1 mm Hg (P<0.01) by the end of the second week and decreased by 25.0/17.9 mm Hg by the end of the 14th weeks. The PWV of all patients decreased by 0.58 m/s after 2-week treatment (P<0.05) and by 0.86 m/s after 14-week treatment (P<0.05). The PWV of those up to standard decreased by 0.55 m/s after 2-week treatment (P<0.05) and by 0.86 m/s after 14-week treatment (P<0.05). Adverse events were observed in 56 patients (21.5%), including headache, flush, and dizziness, however, no severe adverse event was found. No significant changes in laboratory examinations and ECG were found after treatment. CONCLUSION: Slow releasing felodipine is effective in treating mild to moderate primary hypertension, with sustained efficacy of lowering blood pressure and PWV.

[Effect of xinkeshu tablet on heart rate variability in patients with coronary heart disease].

OBJECTIVE: To evaluate the effect of Xinkeshu Tablet (XKS) on heart rate variability (HRV) in patients with coronary heart disease (CHD). METHODS: Sixty patients with their diagnosis of CHD confirmed by coronary angiography were randomized into two groups equally. Besides the conventional treatment for CHD, XKS and Metoprolol were given respectively to patients in the treated group and the control group for 8 weeks. Symptoms and 24 h dynamic ECG were observed before and after treatment. RESULTS: Episode of angina pectoris decreased obviously in both groups after treatment, from 8.8 +/- 3.2 times per week (the same hereafter) to 4.4 +/- 2.1 in the treated group (P<0.05), and from 8.4 +/- 3.1 to 3.9 +/- 2.0 in the control group (P <0.05). HRV analysis showed that after treatment the average heart rate lowered from 85.44 +/- 2.89 beat/min to 77.32 +/- 2.17 beat/min in the treated group and from 83.80 +/- 4.30 beat/min to 76.70 +/- 2.93 beat/min in the control group (both P < 0.05), showing no significant difference in extent of lowering between groups (P > 0.05). The time-domain indexes elevated in both groups, showing no statistical difference between groups (P >0.05). As for the frequency-domain indexes, low frequency (LF), high frequency (HF) and total power raised, while LF/HF and very low frequency lowered in both groups, but the changes were more significant in the treated group (P <0.05). CONCLUSION: XKS could improve HRV in patients of CHD and reduce the episode of angina pectoris in them.

[Association of microalbuminuria and von Willebrand factor with metabolic syndrome in hypertensive patients].

OBJECTIVE: To compare the difference of microalbuminuria (MAU) and von Willebrand factor (vWF) between essential hypertensives and hypertensive patients with metabolic syndrome (MS), and to explore the association of these factors with MS. METHODS: According to the new definition of MS by International Diabetes Federation (IDF) for 2005, 133 consecutive essential hypertensives were divided into two groups: hypertensive patients with metabolic syndrome (EH-MS group, n=97), and essential hypertensives (EH group, n=36). Biochemistry assay, plasma vWF, 24 hours urine albumin excretion (UAE) and morning urine albumin/creatinine ratio (ACR) were measured. The association of MAU and vWF with MS was analysed. RESULTS: Waist circumference, body mass index, triglyceride (TG), low density lipoprotein cholesterol (LDL-C), plasma vWF and UAE were increased(P<0.05 or P<0.01, respectively), while high density lipoprotein cholesterol (HDL-C) was decreased (P<0.01) in EH-MS group, as compared with those in EH group. UAE was positively correlated with ACR (r=0.707, P<0.01). vWF was not correlated with UAE or ACR (r=0.079 and 0.052,P>0.05, respectively). Logistic regression showed HDL-C, TG, LDL-C,vWF and UAE were associated with the development of MS in hypertensive patients (standardized coefficients: -0.825, 0.63, 0.339, 0.331, 0.371,P<0.05 or P<0.01, respectively). CONCLUSION: Compared with essential hypertensives, the hypertensive patients with MS had more MAU and serious endothelial dysfunction. UAE was correlated significantly with ACR. vWF and UAE were associated with the development of MS in patients with hypertension.

[Investigation and screening of glucose metabolism in essential hypertension patients without diagnosed diabetes mellitus].

OBJECTIVE: To obtain the glucose metabolic profile of patients with essential hypertension in China. METHODS: This is an epidemiologic cross-sectional survey and screening study, 5 sites in China participated in. Patients with essential hypertension and without known diabetes mellitus(DM) answered the questionnaire and received in-site fasting blood glucose (FBG) determination and simple oral glucose tolerance test (OGTT). RESULTS: A total of 1,421 patients had the data of FBG and OGTT 2-hour glucose. Among them, The prevalence rates of newly diagnosed DM and impaired glucose regulation (IGR) were 22.9% and 64.4% respectively. Patients with newly diagnosed DM have higher systolic blood pressure, waistline, waist-to-hip ratio and plasma triglyceride. CONCLUSION: Newly diagnosed disturbed glucose metabolic status is common among patients with essential hypertension without DM history, which had very low diagnose rate in routine work. We must pay more attention to the glucose metabolic status of patients with hypertension, especially the one with metabolic syndrome, OGTT should be as a routine procedure in the diagnosis of such patients.

[Effects of Verapamil and Metoprolol on heart rate variability in patients with coronary heart disease].

OBJECTIVE: To evaluate the effects of Verapamil and Metoprolol on improving heart rate variability(HRV) in patients with coronary heart disease (CHD). METHODS: A total of 60 patients, who were diagnosed as CHD according to the results of coronary angiography, were enrolled. All patients were randomly divided into Verapamil group (n=30) and Metoprolol group (n=30). The patients in Verapamil group received Verapamil (480 mg/d) and the patients in Metoprolol group received Metoprolol (50 mg/d) for eight weeks. Office blood pressure, HRV, symptoms of angina Holter recording heart rates per minute and HRV for eight weeks were observed before and after treatment in both groups. RESULTS: Both office blood pressures and the numbers of attacks of angina pectoris and symptoms all decreased obviously in the two groups after treatment. Blood pressures were reduced from 137.12/84.36 mm Hg to 131.80/77.68 mm Hg in Metoprolol group, and also reduced from 137.72/83.92 mm Hg to 129.56/78.76 mm Hg in Verapamil group (P>0.05, compared between the two groups). In both the Verapamil and Metoprolol groups, heart rates decreased, SDNN (standard deviation of all normal to normal RR intervals) and HRVTI (HRV indexes of time-domain) both increased significantly after treatment (P>0.05). And HRV indexes of low-frequency(LF), high-frequency (HF) and total power (TP) were increased obviously, while the low-to high-frequency ratio (LF/HF), very-low-frequency (VLF) were remarkably lower(P<0.05). Compared with Verapamil group, the changes of frequency-domain indexes in Metoprolol group were significant(P<0.05). CONCLUSION: In patients with CHD, both Metoprolol and Verapamil can increase the HRV.

[Efficacy, safety and tolerance of Felodipine controlled release tablets and Felodipine controlled release tablets associated combination therapy in the treatment of mild to moderate essential hypertension in China].

OBJECTIVE: To evaluate the efficacy, safety and tolerance of Felodipine controlled release tablets and Felodipine controlled release tablets associated combination each with Metoprolol, Lisinopril or Hydrochlorothiazide in the 12 weeks treatment of mild to moderate essential hypertension in China. METHODS: Multicenter, random samples, and open study have been processed. RESULTS: (1)After 12 weeks associated combination treatment of anti-hypertension, the percentages of the persons who had attained the target were 80.2% of ITT group in Felodipine controlled release tablets associated combination with Hydrochlorothiazide, 74.1% of ITT group in with Metoprolol,and 80.5% of ITT group in with Lisinopril, respectively. (2)Mean reductions of systolic/diastolic blood pressure from baseline were 16.8/10.6 mm Hg in combination with Hydrochlorothiazide, 16.6/10.7 mm Hg in combination with Metoprolol,and 18.0/12.8 mm Hg in combination with Lisinopril each. There was no significant difference among these three groups (P>0.05). With the Felodipine controlled release tablets treatment alone, the mean reductions from baseline was 24.8/17.5 mm Hg. But in combination with Lisinopril, the blood pressure could lower more quickly, and then could reach the target more rapidly. (3)In the ITT group, the drug compliance with Felodipine controlled release tablets was 97.7%, with those in combination with Hydrochlorothiazide 89.8%, with those in combination with Metoprolol 100.0%, and with those in combination with Lisinopril 96.4%. The main adverse event related to Felodipine was headache, and to Lisinopril was cough. CONCLUSION: Antihypertensive drug Felodipine controlled release tablets are good and effective. And Felodipine controlled release tablet associated combination each with Metoprolol, Lisinopril or Hydrochlorothiazide can make most patients reach the treatment target, with safety, good tolerance, and high compliance.