Improving cardiac function of angiotensin receptor/neprilysin inhibitor in patients with acute myocardial infarction: a systematic review and meta-analysis.

AIM: As the impact of angiotensin receptor/neprilysin inhibitor (ARNI) on cardiac function in acute myocardial infarction (AMI) patients is unclear in clinical therapy, we conducted this research to investigate the actual effects of improving cardiac function with ARNI in AMI patients. METHODS: Publications were checked up to June 2022. Standardised mean differences (SMD) and 95% confidence intervals (CI) were utilised for assessing the size of the effect of continuous variables. To assess the magnitude of the effect of dichotomous variables, a relative risk (RR) with 95% CI was used. RESULTS: ARNI could improve left ventricular ejection fraction (SMD = 0.40; 95% CI: 0.23 - 0.58), while lowering left ventricular end-diastolic volume (SMD = -0.43, 95% CI: -0.78 to -0.08), left ventricular end-systolic volume (SMD = -0.39, 95% CI: -0.66 to -0.11) and left ventricular enddiastolic diameter (SMD = -0.49; 95% CI: -0.65 to -0.33). Besides, it could decrease the rates of major adverse cardiac events (RR = 0.55; 95% CI: 0.43 - 0.69) and heart failure (RR = 0.42; 95% CI: 0.31 - 0.58). CONCLUSION: ARNI could greatly improve cardiac function in AMI patients.

Candesartan cilexetil attenuated cardiac remodeling by improving expression and function of mitofusin 2 in SHR.

BACKGROUND: Left ventricular hypotrophy (LVH) is very common in hypertensives even after antihypertensive treatment. Mitofusin 2 (Mfn2) is a critical negative regulator of vascular smooth muscle cell (VSMC) hypertrophy by regulating mitochondrial fusion, ras/raf/MEK signal pathway, et al. The purpose of this study was to investigate whether candesartan attenuated cardiac remodeling by improving expression and function of mitofusin 2 in SHR. METHODS: Nine weeks old spontaneously hypertensive rats (SHR) were selected and treated with candesartan for eight weeks. Then, heart tissues were investigated for signs of cardiac remodeling, mitochondrial structure and membrane potential, mitochondrial enzyme activities, hydrogen peroxide, mRNA and protein expression of Mfn2/ras/raf/MEK signaling pathway in heart tissues. RESULTS: The results showed that cardiac remodeling was obviously in SHR group: cardiac cell alignment was irregular; cardiac fibers became thick, irregular and enlarged; cell density was reduced in SHR compared to WKY. After candesartan treatment, histopathological structure improved significantly which were consistent with mitochondrial morphology, mitochondrial membrane potential, mitochondrial enzyme activities, hydrogen peroxide, Mfn2/ras/raf/MEK gene and protein expression in cardiac tissues. What's more, although blood pressure was well controlled in a normal range, cardiac remodeling wasn't avoided. In general, candesartan obviously repressed cardiac hypertrophy and cardiac remodeling significantly compared to SHR untreated group, but didn't reverse it. CONCLUSIONS: Mfn2 is negatively associated with cardiac remodeling. Candesartan treatment can improve mitochondrial structure and function and regulate Mfn2/ras/raf/MEK signaling pathway. Mfn2 may be used a potential marker for cardiac remodeling and a novel therapeutic target for target organ damage protection.

Association of echocardiographic left ventricular structure and -344C/T aldosterone synthase gene variant: A meta-analysis.

BACKGROUND: Aldosterone synthase (CYP11B2) is one of the most studied candidate genes related to essential hypertension (EH) and left ventricular hypertrophy (LVH). Some studies have focused on the relationship between -344C/T polymorphism (rs1799998) in the CYP11B2 gene and LVH, but the results are controversial. This meta-analysis is purposed to reveal the relationship between the -344C/T and the left ventricular structure and function, including left ventricular end diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular mass/left ventricular mass index (LVM/LVMI), left ventricular posterior wall thickness (LVPWT), and interventricular septal wall thickness (IVS). METHODS: A literature search of PubMed and Embase databases was conducted on articles published before January 27, 2014. The odds ratios with 95% confidence intervals were calculated. Heterogeneity analyses were performed using meta-regression. Tests for publication bias were also performed and biased studies should be removed from subsequent analyses. RESULTS: There were 20 studies with a total of 6780 subjects meeting the inclusion criteria. The main finding was that concentration levels of LVEDD and LVESD were higher in CC homozygous individuals than in TT homozygous individuals in the whole group. In the Asian subgroup, TT homozygous individuals had larger IVS than CC homozygous individuals. In the Caucasian normotension subgroup, CC homozygous individuals had larger LVM/LVMI than TT homozygous individuals. In the Asian essential hypertension subgroup, TT homozygous individuals had larger LVPWT values than CC homozygous individuals. CONCLUSIONS: The present findings support the hypothesis that CC homozygous individuals may have greater left ventricular diameters (LVEDD and LVESD) regardless of their ethnicities or physical conditions.

[Associations between G1165C and A145G polymorphism of ß1-adrenoceptor and resting heart rate in the Northern Han Chinese].

OBJECTIVE: To systematically investigate the possible associations between G1165C and A145G polymorphism of ß1-adrenoceptor (ADRB1) and resting heart rate (HRrest) in Northern Han Chinese. METHODS: HRrest of 700 healthy Northern Han Chinese were measured in the sitting position.SNPs were genotyped by the TaqMan assay.Genotypes were differentiated by analyzing the fluorescence levels of PCR products using an ABI Prism 7900HT Sequence Detector. RESULTS: HRrest was significantly lower in A145G AA carriers than in AG and GG carriers (all P < 0.01) . Multiple linear regression analysis showed that age, smoking habits, systolic blood pressure, triglyceride, serum creatinine and A145G polymorphism were associated with HRrest (P < 0.01) . A145G was significantly related with HRrest independent of other possible confounding variables, and the partial regression coefficient was 2.148 (P < 0.05) . After adjusting for other confounding factors, significant association between A145G and HRrest was only found in male subjects (P < 0.05) but not in female subjects (P > 0.05) . CONCLUSION: The A145G polymorphism of ADRB1 gene is associated with HRrest in Northern male Han Chinese.

ß1-adrenoceptor gene Arg389Gly polymorphism and essential hypertension risk in general population: a meta-analysis.

The ß1-adrenoceptor (ADRB1) gene Arg389Gly polymorphism has been extensively studied as a candidate gene in essential hypertension (EH), but no consensus has been reached on the relationship between this polymorphism and EH risk. To systematically explore their possible association, a meta-analysis was conducted. All relevant case-control trials in English-language publications before 1 June 2012 were identified by searching the PubMed and Embase databases. Finally, eight articles met our inclusion criteria, including a total of 5,088 patients with EH and 6,515 controls. No evidence of publication bias was found. Fixed-effects model and random-effects model were applied for dichotomous outcomes to combine results from individual studies. Overall, the Gly allelic frequency of Arg389Gly polymorphism was significantly lower in EH subjects than that in controls (Gly versus Arg: P = 0.04, OR = 0.89, 95 % CI [0.80-1.00], P heterogeneity = 0.03, I (2) = 52 %, random-effects model; GlyGly + ArgGly versus ArgArg: P = 0.02, OR = 0.86, 95 % CI [0.76-0.97], P heterogeneity = 0.08 and I (2) = 42 %, random-effect model). Subgroup analysis by ethnicity detected this association only in East Asians. In sensitivity analysis, the study by Bengtsson K was recognized as the main cause of heterogeneity, which was the only one study with the diagnostic standard for EH as systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg. We concluded that the Gly allele of ADRB1 Arg389Gly polymorphism might confer lower risk for EH, especially in East Asians.

A novel 5'-uncoding region -1248 A>G variation of mitofusin-2 gene is associated with hypertension in Chinese.

PURPOSE: Mitofusin2 gene (Mfn2, also named Hyperplasia suppressive gene, HSG) is very important in the origin and development of hypertension. However, the mechanism of Mfn2/HSG expression regulation was not uncovered. This study was designed to explore the association of a novel 5'-uncoding region (UCR) -1248 A>G variation of HSG/Mfn2 gene and hypertension. MATERIALS AND METHODS: 472 healthy, normotensive subjects [normotension (NT) group], 454 prehypertensive subjects [prehypertension (PH) group] and 978 hypertensive patients [essential hypertension (EH) group] were screened for an association study between 5'-UCR -1248 A>G of Mfn2/HSG and hypertension by polymerase chain reaction and DNA sequencing after venous blood was drawn and DNA was extracted. RESULTS: When comparing the A and G frequency in EH, PH and NT groups, in total, NT group significantly had higher A frequency than in PH group [odds ratio (OR)=1.605, confidence interval (CI) 95%=1.063-2.242, p=0.025] and EH group (OR=5.395, CI 95%=3.783-7.695, p<0.01). When subgrouped by gender, A frequency in NT group was still significantly higher than in EH group (male: OR= 4.264, CI 95%=2.780-6.543, p<0.01; female: OR=8.897, CI 95%=4.686-16.891, p<0.01), but not from PH group, either in male group or in female group. Ordinal Logistic Regression analysis showed that A>G variation was significantly related with blood pressure level (B=-1.271, Wald=40.914, CI 95%=-1.660 - -0.881, p<0.01). CONCLUSION: 5'-UCR -1248 A>G variation of Mfn2/HSG gene was a novel variation and may be associated with hypertension in Chinese.

Association between the angiotensinogen gene T174M polymorphism and hypertension risk in the Chinese population: a meta-analysis.

No consensus has been reached on the association between the angiotensinogen gene polymorphism T174M and hypertension risk in the Chinese population. We conducted a meta-analysis to systematically pursue their possible association. Case-control studies in the Chinese and English publications were identified by searching the MEDLINE, EMBASE, CBM, CNKI, Wanfang and VIP databases. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. After this, we selected 16 studies that met the inclusion criteria. In total, the selected studies contributed a study population containing 3828 hypertensive patients and 3251 normotensive controls. We found no statistical association between the T174M polymorphism and hypertension risk in all subjects, in a Han Chinese subgroup or in non-Han Chinese minorities. However, a statistically significant association was observed between the T174M polymorphism and a hypertensive group (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥95 mm Hg) in the dominant genetic model (MM+MT vs. TT: P=0.03, odds ratio=1.71, 95% confidence interval 1.07-2.74, P(heterogeneity)=0.27, I(2)=24%, fixed-effects model). No evidence of publication bias was observed. More studies, especially studies stratified for different stages of hypertension, should be performed in the future to fully examine this question. Studies investigating gene-gene interactions, gene-environment interactions, as well as their mutual interactions will also be important.

[Association of C602A and T1559C polymorphisms of E-selectin gene and essential hypertension].

OBJECTIVE: To investigate the possible genetic associations between the C602A and T1559C polymorphisms of E-selectin (SELE) and essential hypertension. METHODS: Essential hypertensive patients (n = 500) and healthy normotensive subjects (n = 930) were screened for the genotypes C602A and T1559C by real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the SELE gene. RESULTS: Normotensive subjects and hypertensive patients were significantly different with respect to the genotypes CC, CA and AA, 26 (5.2%), 20 (4.0%) and 454 (90.8%) vs 14 (1.5%), 53 (5.7%) and 863 (92.8%) respectively of C602A. And the C-allele frequency was also significantly different between the NT and EH groups (C, A = 7.2%, 92.8% vs 4.4%, 95.6%). When subgrouped by gender, frequency of CC, CA, AA between normotensive and essential hypertensive males was 14 (4.7%), 11 (3.7%), 272 (91.6%) and 10 (1.7%), 34 (5.8%), 545 (92.5%), which differed significantly (P < 0.05), while in female groups, all the frequency of genotypes were significantly different (P < 0.01) except CC + CA. The additive model (TT, TC, CC) of the T1559C genotype was significantly different between essential hypertensive and normotensive groups overall, 57 (11.4%), 200 (40.0%), 43 (48.6%) and 66 (7.1%), 354 (38.1%), 510 (54.8%), respectively. The T-allele of hypertensive patients significantly differed from normotensive subjects (T, C = 31.4%, 68.6% vs 26.1%, 73.9% respectively). When subgrouped by gender, between the male NT and EH groups, the TT, TC and CC frequency of T1559C were 36 (5.9%), 117 (39.4%), 144 (48.5%) and 35 (5.9%), 230 (39.0%), 354 (55.0%), and the frequency of T vs C was 31.4% vs 68.6% and 26.1% vs 73.9%, which were significantly different (all P < 0.01). As in female NT and EH groups, there were not significant differences existed at all. CONCLUSION: C602A and T1559C of SELE are associated with essential hypertension in the Chinese population, and T1559C is closely related with male hypertension other than in females.

Association study of the ß2-adrenergic receptor gene polymorphisms and hypertension in the Northern Han Chinese.

BACKGROUND: The ß2-adrenergic receptor (ADRB2) gene has been widely researched as a candidate gene for essential hypertension (EH), but no consensus has been reached in different ethnicities. The aim of the present study was to evaluate the possible association between the ADRB2 gene polymorphisms and the EH risk in the Northern Han Chinese population. METHODOLOGY/PRINCIPAL FINDINGS: This study included 747 hypertensive subjects and 390 healthy volunteers as control subjects in the Northern Han Chinese. Genotyping was performed to identify the C-47T, A46G and C79G polymorphisms of the ADRB2 gene. G allelic frequency of A46G polymorphism was significantly higher in hypertensive subjects (P = 0.011, OR = 1.287, 95%CI [1.059-1.565]) than that in controls. Significant association could also be found in dominant genetic model (GG+AG vs. AA, P = 0.006, OR = 1.497, 95%CI [1.121-1.998]), in homozygote comparison (GG vs. AA, P = 0.025, OR = 1.568, 95%CI [1.059-2.322]), and in additive genetic model (GG vs. AG vs. AA, P = 0.012, OR = 1.282, 95%CI [1.056-1.555]). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Stratification analyses by obesity showed that A46G polymorphism was related to the prevalence of hypertension in the obese population (GG vs. AG vs. AA, P<0.001, OR = 1.645, 95%CI [1.258-2.151]). Significant interaction was found between A46G genotypes and body mass index on EH risk. No significant association could be found between C-47T or C79G polymorphism and EH risk. Linkage disequilibrium was detected between the C-47T, A46G and C79G polymorphisms. Haplotype analyses observed that the T-47-A46-C79 haplotype was a protective haplotype for EH, while the T-47-G46-C79 haplotype increased the risk. CONCLUSIONS/SIGNIFICANCES: We revealed that the ADRB2 A46G polymorphism might increase the risk for EH in the Northern Han Chinese population.

α-adducin Gly460Trp polymorphism and essential hypertension risk in Chinese: a meta-analysis.

No clear consensus has been reached on the α-adducin polymorphism (Gly460Trp) and essential hypertension (EH) risk in Chinese. We conducted a meta-analysis in an effort to systematically explore the possible association. Case-control studies in Chinese and English performed with human subjects were identified by searching the MEDLINE, EMBASE, China Biological Medicine Database, China National Knowledge Infrastructure platform, Wanfang and VIP databases. The fixed-effects model and the random-effects model for dichotomous outcomes were applied to combine the results of the individual studies. We selected 20 studies that met the inclusion criteria, including a total of 5562 patients with hypertension and 4289 controls. Overall, our findings supported the hypothesis that the ADD1 Gly460Trp polymorphism is associated with EH in the Chinese population. A borderline association was found between the tryptophan (Trp) allele of the Gly460Trp variant and hypertension (P=0.05, Odds ratio (OR)=1.08, 95% confidence interval (CI)=1.00-1.17 and P(heterogeneity)=0.02). Significantly increased risk was observed in the recessive genetic model (P=0.0009, OR=1.24, 95% CI=1.09-1.41 and P(heterogeneity)=0.04) as well as in the homozygote comparison (P=0.006, OR=1.25, 95% CI=1.07-1.46 and P(heterogeneity)=0.03). Furthermore, in the subgroup analysis, our results support a positive association among Chinese Han individuals (P=0.001, OR=1.25, 95% CI=1.09-1.42, P(heterogeneity)=0.08, recessive genetic model; P=0.009, OR=1.26, 95% CI=1.06-1.50, P(heterogeneity)=0.03, homozygote comparison). No apparent association was identified in Kazakhs. Our meta-analysis suggests that the Gly460Trp polymorphism might increase the risk of hypertension in Chinese populations, especially in Han Chinese. Further studies investigating gene-gene, gene-environment and mutual interactions are needed to better understand the role of ADD1 in hypertension.

A-6G and A-20C polymorphisms in the angiotensinogen promoter and hypertension risk in Chinese: a meta-analysis.

BACKGROUND: Numerous studies in Chinese populations have evaluated the association between the A-6G and A-20C polymorphisms in the promoter region of angiotensinogen gene and hypertension. However, the results remain conflicting. We carried out a meta-analysis for these associations. METHODS AND RESULTS: Case-control studies in Chinese and English publications were identified by searching the MEDLINE, EMBASE, CNKI, Wanfang, CBM, and VIP databases. The random-effects model was applied for dichotomous outcomes to combine the results of the individual studies. We finally selected 24 studies containing 5932 hypertensive patients and 5231 normotensive controls. Overall, we found significant association between the A-6G polymorphism and the decreased risk of hypertension in the dominant genetic model (AA+AG vs. GG: P=0.001, OR=0.71, 95%CI 0.57-0.87, P(heterogeneity)=0.96). The A-20C polymorphism was significantly associated with the increased risk for hypertension in the allele comparison (C vs. A: P=0.03, OR=1.14, 95%CI 1.02-1.27, P(heterogeneity)=0.92) and recessive genetic model (CC vs. CA+AA: P=0.005, OR=1.71, 95%CI 1.18-2.48, P(heterogeneity)=0.99). In the subgroup analysis by ethnicity, significant association was also found among Han Chinese for both A-6G and A-20C polymorphisms. A borderline significantly decreased risk of hypertension between A-6G and Chinese Mongolian was seen in the allele comparison (A vs. G: P=0.05, OR=0.79, 95%CI 0.62-1.00, P(heterogeneity)=0.84). CONCLUSION: Our meta-analysis indicated significant association between angiotensinogen promoter polymorphisms and hypertension in the Chinese populations, especially in Han Chinese.

E-selectin gene polymorphisms are associated with essential hypertension: a case-control pilot study in a Chinese population.

BACKGROUND: Genetic variation is thought to contribute to the etiology of hypertension, and E-selectin is a candidate essential hypertension-associated gene. This study thus sought to investigate possible genetic associations between the T1880C, C602A and T1559C polymorphisms of E-selectin and essential hypertension. METHODS: Hypertensive patients (n = 490) and healthy normotensive subjects (n = 495) were screened for the genotypes T1880C, C602A and T1559C using real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the E-selectin gene. The associations between genotypes and alleles of the three mutations and essential hypertension were then analyzed using a case-control study. RESULTS: Hypertensive patients and normotensive subjects were significantly different with respect to the genotypes CC, CA and AA (P = 0.005) and the C-allele frequency of C602A (P = 0.001). A comparison of dominant versus recessive models also revealed significant differences between the two groups (P = 0.004 and P = 0.02). When subgrouped by gender, these indexes differed significantly between normotensive and essential hypertensive males, but not in females. The additive model of the T1559C genotype did not differ between essential hypertensive and normotensive groups overall (P = 0.39), but it was different between hypertensive and normotensive males (P = 0.046) and females (P = 0.045). The CC + TC versus TT frequency of T1559C was also different in the recessive model of male hypertensive and normotensive groups (P = 0.02). Further analysis showed that C602A and T1559C were significantly associated with hypertension (C602A: OR = 7.58, 95%CI = 1.53-11.97, P < 0.01; and T1559C: OR = 6.77, 95%CI = 1.07-1.83, P < 0.05). The frequency of the C-C-C haplotype was significantly higher in hypertensive patients than in control individuals as well as in hypertensive and normotensive males (P = 0.008 and 0.01). The frequency of the C-A-T haplotype was higher only in male hypertensives and normotensives (P = 0.015). Furthermore, there was a significant interaction between E-selectin and gender (P = 0.02 for C602A and 0.04 for T1559C). CONCLUSION: C602A and T1559C may be independent risk factors for essential hypertension in the Chinese population, whereas T1880C is not.