Search

Recent studies have reported the role of the M3 muscarinic acetylcholine receptor (M3R), a member of the G‐protein coupled receptor superfamily, encoded by the CHRM3 gene, in cardiac function and the regulation of blood pressure (BP). The aim of this study was to investigate the associations of CHRM3 genetic variants with salt sensitivity, longitudinal BP changes, and the development of hypertension in a Chinese population. We conducted a chronic dietary salt intervention experiment in a previously established Chinese cohort to analyze salt sensitivity of BP. Additionally, a 14‐year follow‐up was conducted on all participants in the cohort to evaluate the associations of CHRM3 polymorphisms with longitudinal BP changes, as well as the incidence of hypertension. The single nucleotide polymorphism (SNP) rs10802811 within the CHRM3 gene displayed significant associations with low salt‐induced changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), while rs373288072, rs114677844, and rs663148 exhibited significant associations with SBP and MAP responses to a high‐salt diet. Furthermore, the SNP rs58359377 was associated with changes in SBP and pulse pressure (PP) over the course of 14 years. Additionally, the 14‐year follow‐up revealed a significant association between the rs619288 polymorphism and an increased risk of hypertension (OR = 1.74, 95% CI: 1.06‐2.87, p =.029). This study provides evidence that CHRM3 may have a role in salt sensitivity, BP progression, and the development of hypertension. [ABSTRACT FROM AUTHOR]

Normoalbuminuria has recently been associated with increased cardiovascular risk, and vascular aging is proposed as the early manifestation of cardiovascular disease. Here, the authors aimed to examine the association of high‐normal albuminuria and vascular aging in a Chinese cohort. From our previously established cohort, 1942 participants with estimated glomerular filtration rate ≥60 mL/min/1.73 m2 or urinary albumin‐creatinine ratio (UACR) <30 mg/g were enrolled. Brachial‐ankle pulse wave velocity (baPWV) ≥1400 cm/s and/or carotid intima‐media thickness (CIMT) ≥0.9 mm were used as indicators of vascular aging. Multivariate regression and receiving operating characteristic curve analysis were performed to examine the relationship between continuous and categorical UACR with vascular aging. We found an average UACR value of 8.08 (5.45–12.52) mg/g in this study. BaPWV and CIMT demonstrated positive correlations with lg‐UACR (p <.05). High‐normal albuminuria (10–29 mg/g) was significantly associated with the presence of vascular aging after adjusting for multiple cardiovascular confounders (OR = 1.540, 95% CI = 1.203–1.972, p =.001). In addition, a lg‐UACR cutoff point of 0.918 lg(mg/g) (equal to UACR of 8.285 mg/g) was significantly associated with the presence of vascular aging and its components for all participants and those without hypertension or diabetes and without medication (p <.05). Briefly, high‐normal albuminuria was significantly associated with vascular aging in this sample of Chinese adults. These findings implied the warning of elevated UACR even within normal range in clinical practice and the importance of UACR screening in normoalbuminuria for early detection and prevention of cardiovascular disease in otherwise healthy participants. [ABSTRACT FROM AUTHOR]

Neural precursor cell expressed developmentally downregulated 4‐like (NEDD4L), a member of the E3 ubiquitin‐protein ligases, encoded by NEDD4L gene, was found to be involved in in salt sensitivity by regulating sodium reabsorption in salt‐sensitive rats. The authors aimed to explore the associations of NEDD4L genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in Chinese adults. Participants from 124 families in Northern China in the Baoji Salt‐Sensitive Study Cohort in 2004, who received the chronic salt intake intervention, including a 7‐day low‐salt diet (3.0 g/day) and a 7‐day high‐salt diet (18 g/day), were analyzed. Besides, the development of hypertension over 14 years was evaluated. NEDD4L single nucleotide polymorphism (SNP) rs74408486 was shown to be significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low‐salt diet, while SNPs rs292449 and rs2288775 were significantly associated with pulse pressure (PP) response to high‐salt diet. In addition, SNP rs4149605, rs73450471, and rs482805 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP at 14 years of follow‐up. SNP rs292449 was significantly associated with hypertension incidence over the 14‐year follow‐up. Finally, this gene‐based analysis found that NEDD4L was significantly associated with longitudinal BP changes and the incidence of hypertension over the 14‐year follow‐up. This study indicated that gene polymorphism in NEDD4L serve an important function in salt sensitivity, longitudinal BP change and development of hypertension in the Chinese population. [ABSTRACT FROM AUTHOR]

Corin, a transmembrane serine protease that can cleave pro-atrial natriuretic peptide (Pro-ANP) into smaller bioactive molecule atrial natriuretic peptide, has been shown to be involved in the pathophysiology of hypertension, cardiac hypertrophy. We sought to examine the associations of corin genetic variations with salt sensitivity, blood pressure (BP) changes and hypertension incidence. We studied participants of the original Baoji Salt-Sensitive cohort, recruited from 124 families from seven Chinese villages in 2004 who sequentially received a usual baseline salt diet, a 7-day low salt diet (3 g/day) and a 7-day high salt diet (18 g/day), respectively. They were followed up for 8 years (in 2009, 2012) to evaluate the development of hypertension. Corin SNP rs3749584 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) response to low-salt diet, while rs4695253, rs17654278 were associated with pulse pressure (PP) response to low-salt diet. SNPs rs4695253, rs12509275, rs2351783, rs2271036, rs2271037 were significantly associated with systolic BP (SBP), DBP, and MAP responses to high-salt diet. In addition, SNPs rs12641823, rs6834933, rs2271036, and rs22710367 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP over 8 years of follow-up. SNP rs73814824 was significantly associated with the incidence of hypertension over 8 years. Gene-based analysis showed that corin gene was significantly associated with longitudinal BP changes and hypertension incidence after 8-year follow-up. This study suggests that corin may play a role in salt sensitivity, BP progression, and development of hypertension. [ABSTRACT FROM AUTHOR]

The pulsatile stress in the microcirculation may contribute to development or progression of chronic kidney disease. However, there is no prospective data confirming whether pulsatile stress in early life affect renal function in middle age. The authors performed a longitudinal analysis of 1738 participants aged 6–15 years at baseline, an ongoing Adolescent Prospective Cohort with a follow‐up of 30 years. The authors evaluated the association between pulsatile stress in childhood and adult subclinical renal damage (SRD), adjusting for related covariates. Pulsatile stress was calculated as resting heart rate × pulse pressure. Renal function was assessed with estimated glomerular filtration rate (eGFR) and urine albumin‐to‐creatinine ratio (uACR). The results showed that pulsatile stress in childhood was associated with adult SRD (Relative Risk, 1.43; p =.032), and the predictive value of combined pulse pressure and heart rate for SRD was higher than either of them alone. The high pulsatile stress in childhood increased the risk of adult SRD in males (RR, 1.92; p =.003), but this association was not found in females (RR, 0.91; p =.729). Further, the participants were categorized into four groups on the basis of pulsatile stress status in childhood and adulthood. Male patients with high pulsatile stress during childhood but normal pulsatile stress as adults still had an increased risk of SRD (RR, 2.04; 95% CI, 1.18–3.54), while female patients did not (RR, 0.96; 95% CI, 0.46–1.99). The study demonstrated that high pulsatile stress in childhood significantly increased the risk of adult SRD, especially in males. Adequate control of pulse pressure and heart rate from childhood, in the long‐term, is very important for preventing kidney damage. [ABSTRACT FROM AUTHOR]

Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt-Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high-salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high-salt diet than on a low-salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high-salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low-salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations. [ABSTRACT FROM AUTHOR]

Stage 1 hypertension, newly defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guideline, has been the subject of significant interest globally. This study aims to assess the impact of the new blood pressure (BP) stratum on subsequent subclinical cardiovascular outcomes in low‐risk young adults. This longitudinal study consisted of 1020 young adults (47.7% female; ages 18–23 years) free of cardiovascular disease from the Hanzhong Adolescent Hypertension Cohort with up to 25‐year follow‐up since 1992–1995. Outcomes were available through June 2017. Young adults with stage 1 hypertension accounted for 23.7% of the cohort. When it comes to middle adulthood, subjects with early life stage 1 hypertension were more likely to experience BP progression, and they had a 1.61‐fold increased risk of high‐risk brachial‐ankle pulse wave velocity (baPWV) and a 2.92‐fold risk of left ventricular hypertrophy (LVH) comparing with their normotensive counterparts. Among participants without any active treatment in midlife, the risk associated with stage 1 hypertension for BP progression was 2.25 (95% confidence interval [CI] = 1.41–3.59), high‐risk baPWV was 1.58 (95% CI = 1.09–2.79), LVH was 2.75 (95% CI = 1.16–6.48), and subclinical renal damage (SRD) was 1.69 (95% CI = 1.02–2.82) compared with the normal BP group. Overall, young adults with stage 1 hypertension had significantly higher risks for midlife subclinical cardiovascular outcomes than normotensive subjects. BP management targeting low‐risk young adults is of importance from both clinical and public health perspectives. [ABSTRACT FROM AUTHOR]

Pentraxin-3 is a sensitive marker of inflammation that plays dual roles, pathogenic and cardioprotective, in the progression of cardiovascular diseases. Inflammation is intimately involved in salt-induced hypertension. We investigated the responses of pentraxin-3 to sodium and potassium supplementation to elucidate the potential role of pentraxin-3 in salt-induced hypertension. A total of 48 participants from northwest China were enrolled. All participants were maintained on a 3-day normal diet, which was sequentially followed by a 7-day low-sodium diet, a 7-day high-sodium diet, and a 7-day high-sodium plus potassium diet. Plasma concentrations of pentraxin-3 were assessed using ELISA. Plasma pentraxin-3 decreased significantly during the low-salt period compared to baseline (0.57 ± 0.19 ng/mL vs 0.72 ± 0.33 ng/mL, P = .012) and increased during the high-salt period (0.68 ± 0.26 ng/mL vs 0.57 ± 0.19 ng/mL, P = .037). Potassium supplementation inhibited salt-induced increase in pentraxin-3 (0.56 ± 0.21 ng/mL vs 0.68 ± 0.26 ng/mL, P = .015). Ln-transformed pentraxin-3 at baseline was inversely correlated with BMI (r = -.349, P = .02), DBP (r = -.414, P = .005), MAP (r = -.360, P = .017). We found a positive correlation between the ln-transformed concentrations of pentraxin-3 and 24-hour urinary sodium during low and high Na+ periods (r = .269, P = .012) and a negative relationship with 24 hours urinary potassium excretion during high-salt and high-salt plus potassium periods (r = -.246, P = .02). These correlations remained significant after adjusting for confounders. Pentraxin-3 responses were more prominent in salt-sensitive individuals than salt-resistant individuals. Dietary salt and potassium interventions significantly altered circulating pentraxin-3. [ABSTRACT FROM AUTHOR]