Evening versus morning dosing regimen drug therapy for hypertension.

BACKGROUND: Variation in blood pressure levels display circadian rhythms. Complete 24-hour blood pressure control is the primary goal of antihypertensive treatment and reducing adverse cardiovascular outcomes is the ultimate aim. This is an update of the review first published in 2011. OBJECTIVES: To evaluate the effectiveness of administration-time-related effects of once-daily evening versus conventional morning dosing antihypertensive drug therapy regimens on all-cause mortality, cardiovascular mortality and morbidity, total adverse events, withdrawals from treatment due to adverse effects, and reduction of systolic and diastolic blood pressure in people with primary hypertension. SEARCH METHODS: We searched the Cochrane Hypertension Specialised Register via Cochrane Register of Studies (17 June 2022), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2022); MEDLINE, MEDLINE In-Process and MEDLINE Epub Ahead of Print (1 June 2022); Embase (1 June 2022); ClinicalTrials.gov (2 June 2022); Chinese Biomedical Literature Database (CBLD) (1978 to 2009); Chinese VIP (2009 to 7 August 2022); Chinese WANFANG DATA (2009 to 4 August 2022); China Academic Journal Network Publishing Database (CAJD) (2009 to 6 August 2022); Epistemonikos (3 September 2022) and the reference lists of relevant articles. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in people with primary hypertension. We excluded people with known secondary hypertension, shift workers or people with white coat hypertension. DATA COLLECTION AND ANALYSIS: Two to four review authors independently extracted data and assessed trial quality. We resolved disagreements by discussion or with another review author. We performed data synthesis and analyses using Review Manager Web for all-cause mortality, cardiovascular mortality and morbidity, serious adverse events, overall adverse events, withdrawals due to adverse events, change in 24-hour blood pressure and change in morning blood pressure. We assessed the certainty of the evidence using GRADE. We conducted random-effects meta-analysis, fixed-effect meta-analysis, subgroup analysis and sensitivity analysis. MAIN RESULTS: We included 27 RCTs in this updated review, of which two RCTs were excluded from the meta-analyses for lack of data and number of groups not reported. The quantitative analysis included 25 RCTs with 3016 participants with primary hypertension. RCTs used angiotensin-converting enzyme inhibitors (six trials), calcium channel blockers (nine trials), angiotensin II receptor blockers (seven trials), diuretics (two trials), α-blockers (one trial), and ß-blockers (one trial). Fifteen trials were parallel designed, and 10 trials were cross-over designed. Most participants were white, and only two RCTs were conducted in Asia (China) and one in Africa (South Africa). All trials excluded people with risk factors of myocardial infarction and strokes. Most trials had high risk or unclear risk of bias in at least two of several key criteria, which was most prominent in allocation concealment (selection bias) and selective reporting (reporting bias). Meta-analysis showed significant heterogeneity across trials. No RCTs reported on cardiovascular mortality and cardiovascular morbidity. There may be little to no differences in all-cause mortality (after 26 weeks of active treatment: RR 0.49, 95% CI 0.04 to 5.42; RD 0, 95% CI -0.01 to 0.01; very low-certainty evidence), serious adverse events (after 8 to 26 weeks of active treatment: RR 1.17, 95% CI 0.53 to 2.57; RD 0, 95% CI -0.02 to 0.03; very low-certainty evidence), overall adverse events (after 6 to 26 weeks of active treatment: RR 0.89, 95% CI 0.67 to 1.20; I² = 37%; RD -0.02, 95% CI -0.07 to 0.02; I² = 38%; very low-certainty evidence) and withdrawals due to adverse events (after 6 to 26 weeks active treatment: RR 0.76, 95% CI 0.47 to 1.23; I² = 0%; RD -0.01, 95% CI -0.03 to 0; I² = 0%; very low-certainty evidence), but the evidence was very uncertain. AUTHORS' CONCLUSIONS: Due to the very limited data and the defects of the trials' designs, this systematic review did not find adequate evidence to determine which time dosing drug therapy regimen has more beneficial effects on cardiovascular outcomes or adverse events. We have very little confidence in the evidence showing that evening dosing of antihypertensive drugs is no more or less effective than morning administration to lower 24-hour blood pressure. The conclusions should not be assumed to apply to people receiving multiple antihypertensive drug regimens.

Left ventricle hypertrophy and re-modeling in children with essential hypertension: does the race matter?

BACKGROUND: This is the first study to report on the impact of race on differences in the prevalence of echocardiographic left ventricular hypertrophy and left ventricular adaptation at the time of diagnosis of essential hypertension in children. METHODS: This cross-sectional, single-centre study included patients aged 3-18 years who had newly diagnosed essential hypertension. Echocardiography was used to assess left ventricular mass index and left ventricular relative wall thickness. An left ventricular mass index > the 95th percentile for age and gender, and an left ventricular relative wall thickness > 0.42, were used to diagnose left ventricular hypertrophy and concentric adaptation. Various echocardiographic parameters were compared between African Americans and Caucasians. RESULTS: The study included 422 patients (289 African Americans and 133 Caucasians) diagnosed with essential hypertension at a median age of 14.6 (interquartile range; 12.1-16.3) years. Eighty-eight patients (20.9%) had left ventricular hypertrophy. There was no statistically significant difference in the prevalence of left ventricular hypertrophy between African Americans and Caucasians (22.5% versus 17.3%, p=0.22). The median left ventricular relative wall thickness was 0.35 (0.29-0.43), and 114 patients (27.0%) had an left ventricular relative wall thickness > 0.42. The presence of an left ventricular relative wall thickness > 0.42 was significantly higher among African Americans compared to Caucasians (30.1% versus 20.3%, p = 0.04). The African American race was a strong predictor for an left ventricular relative wall thickness > 0.42 (odds ratio 1.7, p = 0.04), but not for left ventricular mass index > the 95th percentile (p = 0.22). Overweight/obesity was a strong predictor for an left ventricular mass index > the 95th percentile. CONCLUSIONS: There was no difference in the prevalence of left ventricular hypertrophy in children with essential hypertension of different races. Obesity, rather than being African American, is associated with left ventricular hypertrophy.

Association between circulatory complement activation and hypertensive renal damage: a case-control study.

OBJECTIVE: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage. METHODS: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected. RESULTS: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD (p < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants (p < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 (p = 0.001) and decreased CFH (p < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 (p = 0.034), elevated AP50 (p < 0.001), decreased CFH (p < 0.001), increased age (p = 0.011) and increased BMI (p = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 (p = 0.017), elevated AP50 (p = 0.023), decreased CFH (p = 0.005) and increased age (p = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants. CONCLUSION: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.

Effects of olmesartan and amlodipine on blood pressure, endothelial function, and vascular inflammation.

BACKGROUND: Anti-hypertensive drugs can improve vascular endothelial function. However, the mechanism remains to be elucidated. OBJECTIVES: This study sought to investigate mechanisms of anti-hypertensive drugs on improvement of vascular endothelial function in patients with essential hypertension. METHODS: Forty-five patients (mean age 58.5 ± 11.2 years) with uncontrolled essential hypertension were randomly assigned to receive olmesartan, an angiotensin II type 1 receptor blocker (ARB) (N = 23), or amlodipine, a calcium channel blocker (CCB) (N = 22), for 6 months. Endothelial function was evaluated by flow-mediated dilatation (FMD) of the brachial artery. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR) within the carotid arteries using 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography. RESULTS: There were no significant differences of baseline clinical data between the ARB and CCB groups. Both anti-hypertensive drugs comparably lowered blood pressure and increased %FMD. TBR values were reduced by olmesartan (P < .001), while blood pressure variability was decreased by amlodipine (P = .004). Changes in %FMD from baseline (Δ%FMD) were inversely associated with ΔTBR in the olmesartan group (r = - .606, P = .003) and with Δsystolic blood pressure variability in the amlodipine group (r = - .434, P = .039). CONCLUSION: Our study indicated that olmesartan and amlodipine could improve endothelial function in patients with essential hypertension in different manners, suppression of vascular inflammation, and decrease in blood pressure variability, respectively.

Correlations of GGT, Hcy and ABI with carotid atherosclerosis in essential hypertension patients.

This study was to explore the correlations of glutamyltransferase (GGT), homocysteine (Hcy) and ankle-brachial index (ABI) with the onset of cervical atherosclerosis (CAS) in essential hypertension (EH) patients. For this purpose, a total of 280 EH patients who were admitted to this hospital or visited the clinic of this hospital were enrolled into the EH group and received the color Doppler ultrasound for carotid artery and biochemical test for blood, and according to the plaques, they were divided into three groups: non-plaque group (n = 113), stable plaque group (n = 102) and non-stable plaque group (n = 65). Simultaneously, 80 healthy subjects who underwent the physical examination were enrolled in the control group. Correlations of GGT, Hcy and ABI with the onset of CAS were analyzed. The results indicated that in the EH group, the prevalence of CAS and Hcy levels were all higher than those in the control group (all P<0.05). As compared to the non-plaque group, patients with stable or non-stable plaques had higher levels of GGT and Hcy in serum but lower levels of ABI (all P<0.05). Logistic regression analysis revealed that CAS plaques were in positive correlation with the levels of GGT and Hcy in serum, but in negative correlation with ABI (P<0.05). In conclusion, ABI is the protective factor of CAS in EH patients, while Hcy and GGT are the negative factors.

Central diastolic blood pressure, plasma aldosterone and uric acid are associated with microalbuminuria in essential hypertension: a case-control study.

OBJECTIVE: To study the development of microalbuminuria (MAU) in essential hypertension (EHT), we investigated the association of MAU with central blood pressure (CBP), direct renin concentration (DRC), plasma aldosterone (PA), and uric acid (UA). METHOD: We determined 24 h-urinary albumin excretion (24 h-UAE) in patients with EHT who were hospitalized at TEDA International Cardiovascular Hospital from June 2020 to May 2022. We defined MAU as 24 h-UAE in the range of 30 mg/24 h to 300 mg/24 h. Univariate and multivariate analyses were conducted to determine the associations of MAU with CBP, DRC, PA, and UA in EHT, considering demographic and clinical information. We also plotted receiver operating characteristic curves (ROCs) for predicting MAU using these results. RESULTS: More than a quarter of patients (26.5%, 107/404, 95% CI: 22.2-31.1%) were diagnosed with MAU in EHT. A higher body mass index (BMI), longer duration of hypertension, and higher severity were associated with MAU. Also, nearly 10% more creatinine levels were recorded in the MAU group than in the control group (69.5 ± 18.7 µmol/L vs. 64.8 ± 12.5 µmol/L, P = 0.004). The increase was also observed for PA (15.5, 9.7-20.6 ng/dL vs. 12.3, 9.0-17.3 ng/dL, P = 0.024) and UA (419.8 ± 105.6 µmol/L vs. 375.1 ± 89.5 µmol/L, P < 0.001) in the MAU group compared to that in the control group. Several variables were associated with MAU, including central diastolic blood pressure (CDBP) (OR = 1.017, 95% CI: 1.002-1.032, P = 0.027), PA (OR = 1.043, 95% CI: 1.009-1.078, P = 0.012) and UA (OR = 1.005, 95% CI: 1.002-1.008, P < 0.001). For MAU prediction, the area under the curve (AUC) was 0.709 (95% CI: 0.662-0.753; P < 0.001) when CDBP, PA, and UA were used in combination, and the optimal probability of the cut-off value was 0.337. CONCLUSION: We found that CDBP, PA, and UA, used for MAU prediction, might be associated with its development during EHT.

Single-Cell Transcriptome Sequencing Reveals Molecular Mechanisms of Renal Injury in Essential Hypertension.

INTRODUCTION: Hypertensive nephropathy is characterized by glomerular and tubulointerstitial damage, but we know little about changes in cell-specific gene expression in the early stages of hypertensive kidney injury, which usually has no obvious pathological changes. METHODS: We performed unbiased single-cell RNA sequencing of rat kidney samples from hypertensive kidney injury to generate 10,602 single-cell transcriptomes from 2 control and 2 early stage hypertensive kidney injury samples. RESULTS: All major cell types of the kidney were represented in the final dataset. Side-by-side comparisons showed that cell type-specific changes in gene expression are critical for functional impairment of glomeruli and tubules and activation of immune cells. In particular, we found a significantly reduced gene expression profile of maintaining vascular integrity in glomerular cells of hypertensive kidney injury. Meanwhile, the expression of genes associated with oxidative stress injury and fibrosis in the renal tubules and collecting ducts was elevated, but the degree of tubular cells response to injury differed between parts. We also found a signature of immune cell infiltration in hypertensive kidney injury. CONCLUSION: Exploring the changes of gene expression in hypertension-injured kidneys may be helpful to identify the early biomarkers and signal pathways of this disease. Our data provide rich resources for understanding the pathogenesis of hypertensive renal injury and formulating effective treatment strategies.

Association of serum transforming growth factor ß1 with left ventricular hypertrophy in children with primary hypertension.

The current study was designed to assess the association of serum transforming growth factor ß1 (TGF-ß1) with left ventricular hypertrophy (LVH) in children with primary hypertension. The present single-center prospective trial examined 182 patients diagnosed with primary hypertension in Children's Hospital, Capital Institute of Pediatrics, between January 2021 and September 2022. Clinical data were analyzed, and ambulatory blood pressure was assessed for 24 h. LVH, the commonest subclinical cardiac feature of hypertension, was assessed by echocardiography. According to left ventricular geometry, cases were assigned to the LVH (n = 44) and normal geometry (n = 138) groups. Serum TGF-ß1 amounts were quantitated by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves were established to analyze various variables for their predictive values in LVH. Among 182 children with primary hypertension, the concentrations of serum TGF-ß1 were higher in stage 2 hypertension than in stage 1 (47.3 (38.8, 52.5) vs. 46.0 (38.6, 48.2) ng/L, Z = - 2.376; P = 0.018). Additionally, serum TGF-ß1 content showed a positive correlation with BP levels (P < 0.05). TGF-ß1 amounts were significantly elevated in the LVH group compared with the normal geometry group (51.7 (46.1, 54.9) vs. 46.1 (38.7, 48.1) ng/L, Z = - 4.324; P = 0.0000). Serum TGF-ß1 content was positively associated with LVH (r = 0.321, P = 0.0000). Multivariable logistic regression analysis showed BMI (OR = 1.188, 95% CI 1.082-1.305; P = 0.0000) and elevated serum TGF-ß1 content (OR = 1.063, 95% CI 1.016-1.113; P = 0.009) independently predicted LVH. A multivariable logistic regression model considering BMI and TGF-ß1 content in LVH prediction was 0.771, with sensitivity and specificity of 72.7% and 70.3%, respectively. CONCLUSION: These data revealed an association of serum TGF-ß1 with BP in children with primary hypertension. Serum TGF-ß1 concentration was positively correlated with hypertensive cardiac damage. Serum TGF-ß1 might constitute a valuable molecular marker for the prediction of LVH in children with primary hypertension. The combination of BMI and TGF-ß1 has a certain diagnostic and predictive value for LVH in children with primary hypertension, which may provide a new reference index for early clinical identification of hypertensive cardiac damage. WHAT IS KNOWN: • Experimental and clinical data indicated TGF-ß1 is involved in BP elevation. • TGF-ß1 is positively correlated with LVMI and hypertrophy in adults. WHAT IS NEW: • Our current study reveals an association of serum TGF-ß1 with BP in children with primary hypertension. • Elevated serum TGF-ß1 level is positively associated with LVH in children with primary hypertension. • The combination of BMI and TGF-ß1 has a certain diagnostic and predictive value for LVH in children with primary hypertension.

The relationship between circadian rhythm of blood pressure and vascular dysfunction in essential hypertension.

OBJECTIVE: This study aimed to explore whether circadian rhythm of blood pressure is associated with brachial-ankle pulse wave velocity (baPWV) and brachial artery flow-mediated dilation (FMD) in patients with essential hypertension. METHOD: This cross-sectional study included 4,217 patients with essential hypertension who completed 24-hour ambulatory blood pressure monitoring, baPWV, and FMD. BaPWV and FMD were measured to evaluate arterial stiffness and endothelial dysfunction. Participants were divided into dipper, non-dipper, and reverse dipping groups according to the nocturnal systolic blood pressure dipping percentage. RESULTS: In this study, baPWV was highest in the reverse dipping groups, followed by non-dipper and dipper groups (1667.11 ± 327.90 vs. 1613.88 ± 325.11 vs. 1577.45 ± 306.15 cm/s, P < .001) and FMD gradually increased (4.41 ± 2.87 vs. 4.70 ± 2.84 vs. 4.92 ± 2.79%, P = .001). baPWV and FMD were significantly associated with declining nocturnal systolic blood pressure (SBP). Interestingly, FMD (ß = 0.042, P = .014) was only positively associated with a drop in nocturnal SBP decline in patients <65 years of age. Whereas baPWV was consistently negatively associated with nocturnal SBP decline regardless of age (ß = -0.065, P < .001, age <65 years; ß = -0.149, P = .002, age ≥ 65). Receiver operating characteristics (ROC) curves analysis showed areas under the curve (AUC) of baPWV/FMD for predicting circadian rhythm of blood pressure are 0.562/0.554 with a sensitivity of 51.7%/53.9% and specificity of 56.4%/53.4. CONCLUSION: Impairment of baPWV and FMD were correlated with abnormal circadian rhythm of blood pressure in essential hypertension, suggesting a decrease in nighttime SBP may associate with endothelial function and arterial stiffness.

Thrombospondin 2 is a novel biomarker of essential hypertension and associated with nocturnal Na+ excretion and insulin resistance.

BACKGROUND: Thrombospondins (TSPs) play important roles in several cardiovascular diseases. However, the association between circulating (plasma) thrombospondin 2 (TSP2) and essential hypertension remains unclear. The present study was aimed to investigate the association of circulating TSP2 with blood pressure and nocturnal urine Na+ excretion and evaluate the predictive value of circulating TSP2 in subjects with hypertension. METHODS AND RESULTS: 603 newly diagnosed essential hypertensive subjects and 508 healthy subjects were preliminarily screened, 47 healthy subjects and 40 newly diagnosed essential hypertensive subjects without any chronic diseases were recruited. The results showed that the levels of circulating TSP2 were elevated in essential hypertensive subjects. The levels of TSP2 positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and other clinical parameters, including homeostasis model assessment of insulin resistance (HOMA-IR), brachial-ankle pulse wave velocity, and serum triglycerides, but negatively associated with nocturnal urine Na+ concentration and excretion and high-density lipoprotein cholesterol. Results of multiple linear regressions showed that HOMA-IR and nocturnal Na+ excretion were independent factors related to circulating TSP2. Mantel-Haenszel chi-square test displayed linear relationships between TSP2 and SBP (χ2 = 35.737) and DBP (χ2 = 26.652). The area under receiver operating characteristic curve (AUROC) of hypertension prediction was 0.901. CONCLUSION: Our study suggests for the first time that the circulating levels of TSP2 may be a novel potential biomarker for essential hypertension. The association between TSP2 and blood pressure may be, at least in part, related to the regulation of renal Na+ excretion, insulin resistance, and/or endothelial function.

Relationship between ambulatory arterial stiffness index and the severity of angiographic atherosclerosis in patients with H-type hypertension and coronary artery disease.

OBJECTIVE: To investigate coronary artery disease (CAD) and its correlation with the ambulatory arterial stiffness index (AASI) in patients with H-type hypertension (essential hypertension combined with hyper-homocysteinemia) and coronary heart disease (CHD). METHODS: Patients with essential hypertension and CHD who were undergoing coronary angiography were enrolled. The general clinical data, biochemical indicators, ambulatory blood pressure monitoring results and coronary angiography results of the selected patients were collected, and the AASI and Gensini scores were calculated. According to homocysteine (Hcy) levels, the patients were divided into two groups: a study group and a control group. The differences in general clinical data, biochemical indexes, AASI scores and degree of coronary artery lesions between the two groups were compared. The correlation between the AASI and the Gensini score and the relationship between the AASI and the Gensini score of CAD and various factors were analyzed. RESULTS: Compared with the control group, the Hcy level in the study group was significantly increased (8.16 ± 2.33 vs 19.20 ± 2.36, P = .001). The 24-h diastolic blood pressure (DBP) in the study group was significantly lower than that in the control group (76.38 ± 9.33 vs 79.91 ± 9.25, P = .002), and the AASI was significantly higher than in the control group (0.62 ± 0.81 vs 0.420 ± 0.70, P = .001). The number of patients having coronary stenoses with a Gensini score of ≤ 38 was significantly lower in the study group than in the control group (21.3% vs 49.4%, P < .001). The number of patients with a Gensini score of ≥ 51 in the study group was significantly higher than in the control group (22.0% vs 18.8%, P < .001). There was a significant positive correlation between the AASI and the Gensini score in the study group (R = 0.732, P < .001). Hypertension duration (ß = 0.168), diabetes history (ß = 0.236), 24-h SBP (ß = 0.122), 24-h DBP (ß = -0.131), low-density lipoprotein cholesterol (ß = 0.134) and Hcy (ß = 0.233) were the influencing factors for AASI (P < .05). Both Hcy * AASI (ß = 0.356) and Hcy × 24-h HR (ß = 0.331) had a synergistic effect on the Gensini score (P = .017), with Hcy * AASI having a more significant effect on the Gensini score (P < .001). CONCLUSION: The AASI was significantly increased in patients with H-type hypertension and CHD, which was associated with the severity of CAD. Therefore, Hcy levels and the AASI have a synergistic effect when evaluating the severity of CAD in patients with hypertensive CHD.

The Effect of Aldosterone on Cardiorenal and Metabolic Systems.

Aldosterone, a vital hormone of the human body, has various pathophysiological roles. The excess of aldosterone, also known as primary aldosteronism, is the most common secondary cause of hypertension. Primary aldosteronism is associated with an increased risk of cardiovascular disease and kidney dysfunction compared to essential hypertension. Excess aldosterone can lead to harmful metabolic and other pathophysiological alterations, as well as cause inflammatory, oxidative, and fibrotic effects in the heart, kidney, and blood vessels. These alterations can result in coronary artery disease, including ischemia and myocardial infarction, left ventricular hypertrophy, heart failure, arterial fibrillation, intracarotid intima thickening, cerebrovascular disease, and chronic kidney disease. Thus, aldosterone affects several tissues, especially in the cardiovascular system, and the metabolic and pathophysiological alterations are related to severe diseases. Therefore, understanding the effects of aldosterone on the body is important for health maintenance in hypertensive patients. In this review, we focus on currently available evidence regarding the role of aldosterone in alterations of the cardiovascular and renal systems. We also describe the risk of cardiovascular events and renal dysfunction in hyperaldosteronism.

Dopamine Receptor D1R and D3R and GRK4 Interaction in Hypertension.

Essential hypertension is caused by the interaction of genetic, behavioral, and environmental factors. Abnormalities in the regulation of renal ion transport cause essential hypertension. The renal dopaminergic system, which inhibits sodium transport in all the nephron segments, is responsible for at least 50% of renal sodium excretion under conditions of moderate sodium excess. Dopaminergic signals are transduced by two families of receptors that belong to the G protein-coupled receptor (GPCR) superfamily. D1-like receptors (D1R and D5R) stimulate, while D2-like receptors (D2R, D3R, and D4R) inhibit adenylyl cyclases. The dopamine receptor subtypes, themselves, or by their interactions, regulate renal sodium transport and blood pressure. We review the role of the D1R and D3R and their interaction in the natriuresis associated with volume expansion. The D1R- and D3R-mediated inhibition of renal sodium transport involves PKA and PKC-dependent and -independent mechanisms. The D3R also increases the degradation of NHE3 via USP-mediated ubiquitinylation. Although deletion of Drd1 and Drd3 in mice causes hypertension, DRD1 polymorphisms are not always associated with human essential hypertension and polymorphisms in DRD3 are not associated with human essential hypertension. The impaired D1R and D3R function in hypertension is related to their hyper-phosphorylation; GRK4γ isoforms, R65L, A142V, and A486V, hyper-phosphorylate and desensitize D1R and D3R. The GRK4 locus is linked to and GRK4 variants are associated with high blood pressure in humans. Thus, GRK4, by itself, and by regulating genes related to the control of blood pressure may explain the "apparent" polygenic nature of essential hypertension.

INFLUENCE OF ESSENTIAL HYPERTENSION ON RIGHT VENTRICULAR MORPHOLOGY AND FUNCTION.

Right ventricular (RV) morphologic and functional changes still remain a mystery in patients with AH. The aim of this study was to evaluate the influence of essential hypertension on RV function and morphology. 75 nonsmoker hypertensive male patients (mean age 57.13±7.27) and 25 normotensive control subjects (mean age 57.56±7.55) were recruited in a study. All participants underwent 24-hour ambulatory blood pressure monitoring. Heart ultrasonography was performed to assess RV morphology and its systolic and diastolic function. In comparison with normotensive subjects, hypertensive patients had significantly higher RV wall thickness and significantly lower TAPSE (5.36±0.98 and 19.86±2.68 vs 4.11±0.50 mm and 22.52±2.02, P<0.0001). RV hypertrophy was found in 38.66% of hypertensive subjects. EF of RV in normotensive subjects was significantly higher than in hypertensives (62.73±12.81 vs 57.58±7.53%, respectively). RV mean E/A was significantly lower in hypertensive group (1.41±0.13 vs 0.89±0.15, P<0.001). RV diastolic dysfunction was found in 54.6% and systolic dysfunction in 7% of hypertensive subjects. The RV E/e' ratio was increased in hypertensives (4.84±0.97 vs. 3.88±0.32 in the control group, P<0.05). Tricuspid and mitral E'/A' ratio was decreased in hypertensive group (0.79±0.13 and 0.90±0.19 in hypertensive vs. 1.21±0.15 and 1.29±0.15 in the control groups, respectively, P<0.001 for both). According to study data, AH affects both ventricles simultaneously and causes concentric remodeling, hypertrophy, and functional disturbances in both ventricles; hence, in comparison with systolic dysfunction, existence of diastolic dysfunction was more prevalent in hypertensive population.

Impact of T2DM on right ventricular systolic dysfunction and interventricular interactions in patients with essential hypertension: evaluation using CMR tissue tracking.

BACKGROUND: Previous studies reported that there was right ventricular (RV) systolic dysfunction in patients with hypertension. The aim of this study was to evaluate the impact of type 2 diabetes mellitus (T2DM) on RV systolic dysfunction and interventricular interactions using cardiac magnetic resonance feature tracking (CMR-FT) in patients with essential hypertension. METHODS AND METHODS: Eighty-five hypertensive patients without T2DM [HTN(T2DM -)], 58 patients with T2DM [HTN(T2DM +)] and 49 normal controls were included in this study. The biventricular global radial, circumferential and longitudinal peak strains (GRS, GCS, GLS, respectively) and RV regional strains at the basal-, mid- and apical-cavity, were calculated with CMR-FT and compared among controls and different patient groups. Backward stepwise multivariable linear regression analyses were used to determine the effects of T2DM and left ventricular (LV) strains on RV strains. RESULTS: The biventricular GLS and RV apical longitudinal strain deteriorated significantly from controls, through HTN(T2DM-), to HTN(T2DM +) groups. RV middle longitudinal strain in patient groups were significantly reduced, and LV GRS and GCS and RV basal longitudinal strain were decreased in HTN(T2DM +) but preserved in HTN(T2DM-) group. Multivariable regression analyses adjusted for covariates demonstrated that T2DM was independently associated with LV strains (LV GRS: ß = - 4.278, p = 0.004, model R2 = 0.285; GCS: ß = 1.498, p = 0.006, model R2 = 0.363; GLS: ß = 1.133, p = 0.007, model R2 = 0.372) and RV GLS (ß = 1.454, p = 0.003, model R2 = 0.142) in hypertension. When T2DM and LV GLS were included in the multiple regression analysis, both T2DM and LV GLS (ß = 0.977 and 0.362, p = 0.039 and < 0.001, model R2 = 0.224) were independently associated with RV GLS. CONCLUSIONS: T2DM exacerbates RV systolic dysfunction in patients with hypertension, which may be associated with superimposed LV dysfunction by coexisting T2DM and suggests adverse interventricular interactions.

Association between Arteriosclerosis and Uncontrolled Blood Pressure in Patients with Essential Hypertension: Cross-Sectional Observational Study Results of the BEST Study.

Whether arteriosclerosis can influence the hypertension control remains incompletely understood. We hypothesized that higher arteriosclerosis may be associated with uncontrolled hypertension. Arteriosclerosis was assessed by carotid femoral artery pulse wave velocity (CF-PWV) and uncontrolled hypertension (systolic blood pressure [BP] ≥130 mm Hg or diastolic BP ≥80 mm Hg). The multivariable-adjusted logistic regression was used for analysis. A total of 1,428 patients with essential hypertension (mean age 68 years, 49.6% male) were enrolled into the study from 2010 to 2017. The BP was uncontrolled in 50.7% of the participants and the mean level of CF-PWV was 12.3 m/s. All the cardiovascular risk factors were worse and CF-PWV was higher in patients with uncontrolled hypertension (all p < 0.05). Multivariable-adjusted logistic regression analysis showed that CF-PWV as a continuous variable (odd ratio [OR] 1.093, 95% confidence interval [CI] 1.046-1.142) was independently associated with uncontrolled hypertension, after male (OR 1.511) and total cholesterol (OR 1.167), followed by body mass index (OR 1.092), fasting plasma glucose (OR 1.075), and creatinine (OR 1.010) (all p < 0.05). As a binary variable, CF-PWV >12 m/s was also independently associated with uncontrolled hypertension (OR 1.690, 95% CI 1.320-2.164, p < 0.05). Arteriosclerosis is independently associated with uncontrolled BP in patients with hypertension.

Analysis of the prevalence, risk factors, and clinical characteristics of osteoporosis in patients with essential hypertension.

BACKGROUND: The present study investigated the prevalence of osteoporosis (OP) among patients with essential hypertension (EH) in the Changchun community and analysed the correlation between EH and OP. METHODS: The study included 425 subjects with EH and 425 age- and sex-matched healthy controls. Bone mineral density (BMD) and serum creatinine (CR) levels were measured, and the subjects' current EH and OP statuses were surveyed to analyse the correlation between EH and OP. RESULTS: The EH group exhibited lower BMD and a higher rate of having OP than the control group, and this difference was statistically significant (p < 0.05). A significant sex difference in the BMD T-score was observed among the subjects (male: - 1.19 ± 1.55, female: - 1.70 ± 1.34). In both the EH group and the control group, the rate of having OP in females was greater than that in males. However, the OP prevalence among subjects with EH varied significantly by age, body weight, fracture history, nocturnal urination frequency, depression and anxiety status, duration of hypertension, and antihypertensive medication use (p < 0.05). Two-way analysis of variance suggested an effect of the interaction between different EH statuses and bone mass conditions on the serum CR values (F = 3.584, p = 0.028, bias η2 = 0.008). CONCLUSIONS: The prevalence of OP and low BMD were significantly higher among subjects with EH than among healthy controls. Additionally, the findings indicate that age, weight, fracture history, nocturnal urination frequency, depression and anxiety, duration of hypertension and antihypertensive drug use may be correlated to having OP in EH subjects, requiring further studies. Moreover, serum CR levels in subjects with different bone mass profiles were strongly influenced by the presence or absence of EH, and the serum CR levels differed significantly with the interaction of these two factors.

Novel insights into the association between seasonal variations, blood pressure, and blood pressure variability in patients with new-onset essential hypertension.

BACKGROUND: Blood pressure (BP) exhibits seasonal variations, with peaks reported in winter. However, the association between seasonal variations and blood pressure variability in patients with new-onset essential hypertension is not fully understood. This study evaluated the potential association of seasonal variations with new-onset essential hypertension. METHODS: This retrospective observational study recruited a total of 440 consecutive patients with new-onset essential hypertension who underwent 24-h ambulatory electrocardiograph (ECG) and BP measurement at our department between January 2019 and December 2019. Demographic and baseline clinical data including BP variability, heart rate variability, and blood tests were retrieved. Multivariate linear regression analysis was performed to identify factors independently associated with mean BP and BP variability. RESULTS: Among the 440 patients recruited, 93 cases were admitted in spring, 72 in summer, 151 in autumn, and 124 in winter. Univariate analysis revealed that systolic BP (SBP), diastolic BP (DBP), high-sensitivity C-reactive protein, SBP drop rate, DBP drop rate, 24-h standard deviation of SBP, 24-h standard deviation of DBP, 24-h SBP coefficient of variation, and 24-h DBP coefficient of variation were associated with patients admitted in winter (P < 0.05 for all). Multivariate linear regression analysis showed that winter was the influencing factor of 24-h standard deviation of SBP (B = 1.851, t = 3.719, P < 0.001), 24-h standard deviation of DBP (B = 1.176, t = 2.917, P = 0.004), 24-h SBP coefficient of variation (B = 0.015, t = 3.670, P < 0.001), and 24-h DBP coefficient of variation (B = 0.016, t = 2.849, P = 0.005) in hypertensive patients. CONCLUSIONS: Seasonal variations are closely associated with BP variability in patients with new-onset essential hypertension. Our study provides insight into the underlying pathogenesis of new-onset essential hypertension.

Association between AT1 receptor gene polymorphism and left ventricular hypertrophy and arterial stiffness in essential hypertension patients: a prospective cohort study.

BACKGROUND: AT1 receptor gene (AGTR1) is related to essential hypertension (EH), and left ventricular hypertrophy (LVH) and arterial stiffness are common complications of EH. This study aimed to explore the association between AGTR1 genotype and LVH and arterial stiffness in EH patients. METHODS: A total of 179 EH patients were recruited in this study. Oral exfoliated cells were collected from each patient, and the genetic polymorphism of AGTR1(rs4524238) was assessed using a gene sequencing platform. The outcomes were LVH and arterial stiffness. RESULTS: Among 179 patients, 114 were with AGTR1 genotype of GG (57 males, aged 59.54 ± 13.49 years) and 65 were with AGTR1 genotype of GA or AA (36 males, aged 61.28 ± 12.79 years). Patients with AGTR1 genotype of GG were more likely to have LVH (47 [41.23%] vs. 14 [21.54%], P = 0.006) and arterial stiffness (30 [26.32%] vs. 8 [12.31%], P = 0.036). The AGTR1 polymorphism frequency was in accordance with Hardy-Weinberg equilibrium (P = 0.291). The multivariate logistic regression showed that AGTR1 genotype of GA or AA was independently associated with lower risk of LVH (OR = 0.344, 95%CI 160~0.696, P = 0.003) and arterial stiffness (OR = 0.371, 95%CI 0.155~0.885, P = 0.025) after adjusting for gender, age, and diabetes. CONCLUSION: EH patients with the AGTR1 genotype of GA or AA were at lower risk for LVH and arterial stiffness than those with the GG genotype.

Association between Vitamin D Deficiency and Levels of Renin and Angiotensin in Essential Hypertension.

Objective: The present study aims to investigate the relationship between vitamin D deficiency and renin-angiotensin-aldosterone levels in patients with essential hypertension. Methods: The present study observed two groups of patients from Urumqi, Xinjiang, China, from April 2017 to March 2018. There were two subject groups: the hypertension group (80 patients with essential hypertension selected by random cluster sampling) and the control group (76 healthy adults). The 25-hydroxyvitamin D (25(OH)D or vitamin D) levels were measured through electrolytes; fasting blood glucose, blood lipids, and other biochemical indicators were detected using immune chemiluminescence; and plasma renin activity and angiotensin II concentrations were detected with radio-immunity. Results: Comparison between the hypertension group and control group showed statistically significant differences in the systolic pressure and levels of 25(OH)D, renin, and triglycerides (P < 0.05). The correlation analysis showed that 25(OH)D was negatively correlated with renin (r = -0.185; P=0.021) and positively correlated with systolic pressure (r = -0.105; P=0.035). There were no statistically significant differences in diastolic pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides between the two groups. Conclusions: The results of the present study show that vitamin D deficiency is common in Urumqi, Xinjiang, China and vitamin D levels are negatively correlated with renin levels. Vitamin D plays an important role in regulating blood pressure by affecting renin levels through the renin-angiotensin-aldosterone system.