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1.
EClinicalMedicine ; 69: 102486, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38370536

RESUMO

Background: Limited data exists on how early-life weight changes relate to metabolic syndrome (MetS) risk in midlife. This study examines the association between long-term trajectories of body mass index (BMI), its variability, and MetS risk in Chinese individuals. Methods: In the Hanzhong Adolescent Hypertension study (March 10, 1987-June 3, 2017), 1824 participants with at least five BMI measurements from 1987 to 2017 were included. Using group-based trajectory modeling, different BMI trajectories were identified. BMI variability was assessed through standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Logistic regression analyzed the relationship between BMI trajectory, BMI variability, and MetS occurrence in midlife (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02734472). Findings: BMI trajectories were categorized as low-increasing (34.4%), moderate-increasing (51.8%), and high-increasing (13.8%). Compared to the low-increasing group, the odds ratios (ORs) [95% CIs] for MetS were significantly higher in moderate (4.27 [2.63-6.91]) and high-increasing groups (13.11 [6.30-27.31]) in fully adjusted models. Additionally, higher BMI variabilities were associated with increased MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 2.30 [2.02-2.62], 1.22 [1.19-1.26], and 4.29 [3.38-5.45]). Furthermore, BMI trajectories from childhood to adolescence were predictive of midlife MetS, with ORs in moderate (1.49 [1.00-2.23]) and high-increasing groups (2.45 [1.22-4.91]). Lastly, elevated BMI variability in this period was also linked to higher MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 1.24 [1.08-1.42], 1.00 [1.00-1.01], and 1.21 [1.05-1.38]). Interpretation: Our study suggests that both early-life BMI trajectories and BMI variability could be predictive of incident MetS in midlife. Funding: This work was supported by the National Natural Science Foundation of China No. 82070437 (J.-J.M.), the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University of China (No. XJTU1AF-CRF-2022-002, XJTU1AF2021CRF-021, and XJTU1AF-CRF-2023-004), the Key R&D Projects in Shaanxi Province (Grant No. 2023-ZDLSF-50), the Chinese Academy of Medical Sciences & Peking Union Medical College (2017-CXGC03-2), and the International Joint Research Centre for Cardiovascular Precision Medicine of Shaanxi Province (2020GHJD-14).

2.
J Clin Hypertens (Greenwich) ; 26(1): 36-46, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38010846

RESUMO

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.


Assuntos
Hipertensão , Adulto , Humanos , Pressão Sanguínea/genética , Hipertensão/epidemiologia , Hipertensão/genética , Cloreto de Sódio na Dieta/efeitos adversos , Incidência , Polimorfismo de Nucleotídeo Único , China/epidemiologia , Receptor Muscarínico M3/genética
3.
J Clin Hypertens (Greenwich) ; 25(12): 1096-1104, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37966821

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Hipertensão , Adulto , Humanos , Adolescente , Espessura Intima-Media Carotídea , Doenças Cardiovasculares/complicações , Fatores de Risco , Índice Tornozelo-Braço , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Albuminúria/complicações , Creatinina , Análise de Onda de Pulso , Taxa de Filtração Glomerular , Envelhecimento
4.
Front Endocrinol (Lausanne) ; 14: 1164592, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795361

RESUMO

Background and aims: Obesity is an independent risk factor for cardiovascular disease development. Here, we aimed to examine and compare the predictive values of three novel obesity indices, lipid accumulation product (LAP), visceral adiposity index (VAI), and triglyceride-glucose (TyG) index, for cardiovascular subclinical organ damage. Methods: A total of 1,773 healthy individuals from the Hanzhong Adolescent Hypertension Study cohort were enrolled. Anthropometric, biochemical, urinary albumin-to-creatinine ratio (uACR), brachial-ankle pulse wave velocity (baPWV), and Cornell voltage-duration product data were collected. Furthermore, the potential risk factors for subclinical organ damage were investigated, with particular emphasis on examining the predictive value of the LAP, VAI, and TyG index for detecting subclinical organ damage. Results: LAP, VAI, and TyG index exhibited a significant positive association with baPWV and uACR. However, only LAP and VAI were found to have a positive correlation with Cornell product. While the three indices did not show an association with electrocardiographic left ventricular hypertrophy, higher values of LAP and TyG index were significantly associated with an increased risk of arterial stiffness and albuminuria. Furthermore, after dividing the population into quartiles, the fourth quartiles of LAP and TyG index showed a significant association with arterial stiffness and albuminuria when compared with the first quartiles, in both unadjusted and fully adjusted models. Additionally, the concordance index (C-index) values for LAP, VAI, and TyG index were reasonably high for arterial stiffness (0.856, 0.856, and 0.857, respectively) and albuminuria (0.739, 0.737, and 0.746, respectively). Lastly, the analyses of continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) demonstrated that the TyG index exhibited significantly higher predictive values for arterial stiffness and albuminuria compared with LAP and VAI. Conclusion: LAP, VAI, and, especially, TyG index demonstrated utility in screening cardiovascular subclinical organ damage among Chinese adults in this community-based sample. These indices have the potential to function as markers for early detection of cardiovascular disease in otherwise healthy individuals.


Assuntos
Doenças Cardiovasculares , Produto da Acumulação Lipídica , Adulto , Humanos , Adiposidade , Albuminúria/diagnóstico , Índice Tornozelo-Braço , Glicemia/análise , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , População do Leste Asiático , Glucose , Obesidade , Análise de Onda de Pulso , Triglicerídeos
5.
Hypertens Res ; 46(7): 1795-1803, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37160967

RESUMO

Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowers blood pressure (BP) and exert a salutary effect on the salt sensitivity of BP. This study aimed to examine the associations of SGLT2 genetic variants with salt sensitivity, longitudinal BP changes and the risk of incident hypertension in Baoji Salt-Sensitive Study. A total of 514 participants were recruited when the cohort was established in 2004, and 333 participants received a dietary intervention that consisted of a 3-day usual diet followed sequentially by a 7-day low-salt diet and a 7-day high-salt diet. The cohort was then followed up for 14 years to evaluate the longitudinal BP changes and development of hypertension. We found that SGLT2 SNP rs3813007 was significantly associated with the systolic BP (SBP) responses to the low-salt diet. Over the 14 years of follow-up, SNPs rs3116149 and rs3813008 were significantly associated with the longitudinal SBP changes, and SNPs rs3116149, rs3813008, rs3813007 in SGLT2 were significantly associated with incidence of hypertension. Furthermore, gene-based analyses revealed that SGLT2 was significantly associated with hypertension incidence. Our study suggests that SGLT2 genetic polymorphisms may be involved in salt sensitivity and development of hypertension.


Assuntos
Pressão Sanguínea , População do Leste Asiático , Hipertensão , Cloreto de Sódio na Dieta , Adulto , Humanos , Pressão Sanguínea/fisiologia , Hipertensão/epidemiologia , Hipertensão/etiologia , Hipertensão/genética , Incidência , Polimorfismo de Nucleotídeo Único , Cloreto de Sódio na Dieta/efeitos adversos , Transportador 2 de Glucose-Sódio/genética
6.
Hypertension ; 80(5): 1057-1066, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36880389

RESUMO

BACKGROUND: Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife. METHODS: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years. Distinct trajectories of systolic blood pressure (SBP), body mass index (BMI), and heart rate from childhood to midlife were identified by group-based trajectory modeling. Vascular aging was assessed by carotid intima media thickness or brachial-ankle pulse wave velocity. RESULTS: We identified 4 distinct SBP trajectories, 3 distinct BMI trajectories, and 2 distinct heart rate trajectories from childhood to midlife. Persistently increasing SBP, high-increasing BMI, and high-stable heart rate were all shown to have a positive association with brachial-ankle pulse wave velocity in midlife. For carotid intima-media thickness, similar associations were observed for persistently increasing SBP and high-increasing body mass index. After further adjustment for SBP, body mass index and heart rate at the time of vascular assessment in 2017, associations were also observed for cardiovascular risk factor trajectories accumulation with brachial-ankle pulse wave velocity (ß, 0.656 [95% CI, 0.265-1.047]) and with carotid intima media thickness (ß, 0.045 [95% CI, 0.011-0.079]) in adulthood. CONCLUSIONS: Longitudinal exposure to individual cardiovascular risk factors from childhood to midlife and cardiovascular risk factor accumulation were associated with an increased risk of vascular aging in midlife. Our study lends support for early targeting of risk factors in order to prevent cardiovascular disease later in life.


Assuntos
Doenças Cardiovasculares , Adolescente , Humanos , Criança , Espessura Intima-Media Carotídea , Índice Tornozelo-Braço , Estudos Prospectivos , Fatores de Risco , Análise de Onda de Pulso , Envelhecimento/fisiologia , Pressão Sanguínea/fisiologia , Fatores de Risco de Doenças Cardíacas
7.
J Clin Hypertens (Greenwich) ; 24(10): 1381-1389, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36039789

RESUMO

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.


Assuntos
Hipertensão , Ubiquitina-Proteína Ligases Nedd4 , Humanos , Pressão Sanguínea/genética , China/epidemiologia , Hipertensão/epidemiologia , Hipertensão/genética , Incidência , Polimorfismo de Nucleotídeo Único , Sódio , Cloreto de Sódio na Dieta/efeitos adversos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases Nedd4/genética
8.
EClinicalMedicine ; 48: 101420, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35516445

RESUMO

Background: Albuminuria is a marker of vascular dysfunction and is associated with chronic renal and cardiovascular diseases. Data on the association between the longitudinal patterns of weight change early in life and albuminuria later in life are limited. We aimed to identify the body mass index (BMI) trajectory across a 30-year span and evaluate its association with middle-age albuminuria. Methods: Of the 4623 participants aged 6-18-year-old recruited by Hanzhong Adolescent Hypertension Study cohort in northern China from March 10, 1987 to June 3, 2017, a total of 1,825 participants followed up with 6 visits over 30 years were enrolled. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analyses. Albuminuria was defined as a urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. Findings: Three distinct BMI trajectories were identified: low-increasing (n = 671, 36.8%), moderate-increasing (n = 940, 51.5%), and high-increasing (n = 214, 11.7%); male participants exhibited a steeper increase in BMI than females. The uACR was increased linearly from the low- to high-increasing group. A total of 201 individuals developed albuminuria, with an incidence of 11.0%. Compared with the low-increasing group, the odds ratio (OR) of albuminuria in middle age was 2.13(95% confidence interval [CI]: 1.26 to 3.61) for the high-increasing group after full adjustment for age, sex, smoking, alcohol consumption, marital status, systolic blood pressure, diabetes, and hyperlipidemia. The unadjusted ORs of the high-increasing BMI group were 5.08 (2.76-9.37) for males and 3.45 (1.78-6.69) for females, and the association remained significant in males in the fully adjusted models. Interpretation: Higher BMI trajectories are associated with higher uACR and an increased risk of albuminuria in middle age, especially in males. Identifying long-term BMI trajectories from an early age may assist in predicting the risk of renal diseases and cardiovascular disease later in life. Funding: This work was supported by the National Natural Science Foundation of China (81600327, 82070437, 81870319, 82070549, and 82170437), Natural Science Basic Research Program of Shaanxi Province (2021JM-257 and 2021JM-588), Institutional Foundation of the First Affiliated Hospital of Xi'an Jiaotong University (2019QN-06 and 2021ZXY-14), the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University of China (XJTU1AF-CRF-2019-004, XJTU1AF2021CRF-021, and XJTU1AFCRF-2017-021), Research Incubation Fund of Xi'an People's Hospital (FZ-61), Grants from the Major Chronic Non-communicable Disease Prevention and Control Research Key Project of the Ministry of Science and Technology of China (2017YFC1307604 and 2016YFC1300104).

9.
Hypertension ; 79(6): 1247-1256, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35360932

RESUMO

BACKGROUND: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with risk of cardiovascular disease. We, therefore, aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood. METHODS: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BPV by SD and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate between 30 and 60 mL/min per 1.73 m2 or elevated urinary albumin-to creatinine ratio at least 30 mg/g. Albuminuria was defined as urinary albumin-to creatinine ratio ≥30 mg/g. RESULTS: During 30 years of follow-up, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics, and mean BP during 30 years, higher SDSBP , ARVSBP , SDDBP , ARVDBP , SDMAP , ARVMAP , and ARVPP were significantly associated with higher risk of SKD. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria. Long-term BPV from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up. CONCLUSIONS: Identifying long-term BPV from early age may assist in predicting kidney disease and cardiovascular disease in later life.


Assuntos
Pressão Sanguínea , Hipertensão , Nefropatias , Adolescente , Adulto , Albuminas , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Albuminúria/etiologia , Doenças Cardiovasculares , Criança , Creatinina , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Rim , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Nefropatias/etiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
10.
Front Cardiovasc Med ; 9: 800427, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35282385

RESUMO

Objective: Renalase, a novel secretory flavoprotein with amine oxidase activity, is secreted into the blood by the kidneys and is hypothesized to participate in blood pressure (BP) regulation. We investigated the associations of renalase with BP and the risk of hypertension by examining renalase single nucleopeptide polymorphism (SNPs), serum renalase levels, and renal expression of renalase in humans. Methods: ① Subjects (n = 514) from the original Baoji Salt-Sensitive Study cohort were genotyped to investigate the association of renalase SNPs with longitudinal BP changes and the risk of hypertension during 14 years of follow-up. ② Two thousand three hundred and ninety two participants from the Hanzhong Adolescent Hypertension Study cohort were used to examine the association of serum renalase levels with hypertension. Renalase expression in renal biopsy specimens from 193 patients were measured by immunohistochemistry. ③ Renalase expression was compared in hypertensive vs. normotensive patients. Results: ① SNP rs7922058 was associated with 14-year change in systolic BP, and rs10887800, rs796945, rs1935582, rs2296545, and rs2576178 were significantly associated with 14-year change in diastolic BP while rs1935582 and rs2576178 were associated with mean arterial pressure change over 14 years. In addition, SNPs rs796945, rs1935582, and rs2576178 were significantly associated with hypertension incidence. Gene-based analysis found that renalase gene was significantly associated with hypertension incidence over 14-year follow-up after adjustment for multiple measurements. ② Hypertensive subjects had higher serum renalase levels than normotensive subjects (27.2 ± 0.4 vs. 25.1 ± 0.2 µg/mL). Serum renalase levels and BPs showed a linear correlation. In addition, serum renalase was significantly associated with the risk of hypertension [OR = 1.018 (1.006-1.030)]. ③ The expression of renalase in human renal biopsy specimens significantly decreased in hypertensive patients compared to non-hypertensive patients (0.030 ± 0.001 vs. 0.038 ± 0.004). Conclusions: These findings indicate that renalase may play an important role in BP progression and development of hypertension.

11.
Front Cardiovasc Med ; 8: 710023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869624

RESUMO

Background: Uromodulin, also named Tamm Horsfall protein, has been associated with renal function and regulation of sodium homeostasis. We aimed to examine the associations of serum uromodulin levels and its genetic variants with longitudinal blood pressure (BP) changes and hypertension incidence/risk. Methods: A total of 514 participants from the original Baoji Salt-Sensitive Study cohort were genotyped to examine the associations of genetic variations in uromodulin gene with the longitudinal BP changes and the incidence of hypertension over 8 years of follow-up. In addition, 2,210 subjects from the cohort of Hanzhong Adolescent Hypertension Study were used to investigate the relationships between serum uromodulin levels and the risk of hypertension. Results: SNPs rs12917707 and rs12708631 in the uromodulin gene were significantly associated with the longitudinal BP changes over 8 years of follow-up. SNP rs12708631 was significantly associated with the incidence of hypertension over 8 years. In addition, gene-based analyses supported the associations of uromodulin gene with the longitudinal BP changes and hypertension incidence in Baoji Salt-Sensitive Study cohort. Furthermore, serum uromodulin levels in the hypertensive subjects were lower than in the normotensive subjects (25.5 ± 1.1 vs. 34.7 ± 0.7 ng/mL). Serum uromodulin levels decreased gradually as BP levels increased (34.6, 33.2, 27.8, and 25.0 ng/mL for subjects with normotension, high-normal, grade 1 hypertension, and grade 2 hypertension, respectively). Serum uromodulin was significantly associated with the lower risk of hypertension [0.978 (0.972-0.984)] in Hanzhong Adolescent Hypertension Study cohort. Conclusion: This study shows that uromodulin is associated with blood pressure progression and development of hypertension.

12.
J Clin Hypertens (Greenwich) ; 23(12): 2115-2123, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34846782

RESUMO

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.


Assuntos
Hipertensão , Serina Endopeptidases , Adulto , Pressão Sanguínea/genética , China/epidemiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Incidência , Polimorfismo de Nucleotídeo Único , Serina Endopeptidases/genética
13.
J Clin Hypertens (Greenwich) ; 23(10): 1897-1906, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34363725

RESUMO

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.


Assuntos
Hipertensão , Cloreto de Sódio na Dieta , Adulto , Pressão Sanguínea/genética , Dieta Hipossódica , Humanos , Hipertensão/genética , Cloreto de Sódio na Dieta/efeitos adversos , Uromodulina/genética
14.
J Hypertens ; 39(9): 1817-1825, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33783375

RESUMO

OBJECTIVE: Pregnancy-associated plasma protein-A2 (PAPP-A2) is the homolog of PAPP-A in the vertebrate genome and its role in protecting against salt-induced hypertension in salt-sensitive rats has been confirmed. We sought to examine the associations of plasma PAPP-A2 levels and its genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in humans. METHODS: Eighty participants (18-65 years old) sequentially consuming a usual diet, a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day). In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families in Northern China in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension over 14 years. RESULTS: The plasma PAPPA2 levels significantly decreased with the change from baseline to a low-salt diet and decreased further when converting from the low-salt to high-salt diet. SNP rs12042763 in the PAPP-A2 gene was significantly associated with systolic BP responses to both low-salt and high-salt diet while SNP rs2861813 showed a significant association with the changes in SBP and pulse pressure at 14-year follow-up. Additionally, SNPs rs2294654 and rs718067 demonstrated a significant association with the incidence of hypertension over the 14-year follow-up. Finally, the gene-based analysis found that Pappa2 was significantly associated with longitudinal SBP changes and the incidence of hypertension over the 14-year follow-up. CONCLUSIONS: This study shows that dietary salt intake affects plasma PAPP-A2 levels and that PAPP-A2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations.


Assuntos
Hipertensão , Cloreto de Sódio na Dieta , Adulto , Animais , Pressão Sanguínea/genética , Proteínas Sanguíneas , China/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Incidência , Piperazinas , Polimorfismo de Nucleotídeo Único , Gravidez , Ratos
15.
Eur J Clin Nutr ; 75(3): 531-538, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32994554

RESUMO

BACKGROUND/OBJECTIVES: Chronic kidney disease (CKD) is a global public health problem, including in China. The aim of this study was to identify the risk factors for the development and progression of subclinical renal disease (SRD) in a Chinese population. We also examined whether the impact of the risk factors on SRD changed over time. SUBJECTS/METHODS: To identify the predictors of SRD, we performed a cross-sectional study of the 2432 subjects in our Hanzhong Adolescent Hypertension Cohort. A subgroup of 202 subjects was further analyzed over a 12-year period from 2005 to 2017 to determine the risk factors for the development and progression of SRD. RESULTS: In cross-sectional analysis, elevated blood pressure, male gender, diabetes, body mass index, and triglyceride were independently associated with a higher risk of SRD. In longitudinal analysis, an increase in total cholesterol over a 4-year period and an increase in serum triglyceride over a 12-year period were independently associated with progression of albuminuria. Finally, increases in both total cholesterol and serum uric acid over a 4-year follow-up showed an independent association with a modest reduction in estimated glomerular filtration rate (eGFR). CONCLUSIONS: In this study of a Chinese cohort, we show several metabolic abnormalities as independent risk factors for subclinical renal disease in a Chinese cohort. In addition, we demonstrate that the effects of total cholesterol, triglycerides and uric acid on the development and progression of albuminuria or the decline in eGFR vary at different points of follow-up. These findings highlight the importance of early detection of metabolic abnormalities to prevent SRD.


Assuntos
Hipertensão , Insuficiência Renal Crônica , Adolescente , China/epidemiologia , Estudos Transversais , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Masculino , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Fatores de Risco , Ácido Úrico
16.
Dis Markers ; 2020: 1638515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32724482

RESUMO

BACKGROUND: Hyperuricemia has long been associated with increased cardiovascular risk, and arterial stiffness is proposed as a mediator. The present study is aimed at examining the associations of uric acid (UA) in blood and urine with arterial stiffness in a Chinese cohort. METHODS: A total of 2296 participants (mean age: 43.0 years) from our previously established cohort of Hanzhong Adolescent Hypertension Study were included. The participants were classified as subjects with or without arterial stiffness, which was defined as brachial-ankle pulse wave velocity (baPWV) ≥ 1400 cm/s and/or carotid intima-media thickness (CIMT) ≥ 0.9 mm. Multivariate regression analyses were used to examine the relationship between serum and urinary UA and the risk of arterial stiffness after adjusting for age, gender, systolic blood pressure, fasting glucose, BMI, heart rate, total cholesterol, and triglycerides. RESULTS: baPWV was positively correlated with urinary uric acid/creatinine ratio (uUA/Cre) (ß = 0.061, P < 0.001), while CIMT was correlated with uUA/Cre (ß = 0.085, P < 0.001) and fractional excretion of uric acid (FEUA) (ß = 0.044, P = 0.033) in all subjects. In addition, uUA/Cre was significantly associated with the risk of high baPWV [1.032 (1.019-1.045)] and arterial stiffness [1.028 (1.016-1.040)]. CONCLUSION: Our study showed that urinary UA excretion was significantly associated with the risk of arterial stiffness in Chinese adults. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of arterial stiffness in otherwise healthy subjects.


Assuntos
Doenças Cardiovasculares/diagnóstico , Ácido Úrico/sangue , Ácido Úrico/urina , Rigidez Vascular , Adolescente , Adulto , Índice Tornozelo-Braço , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/urina , Espessura Intima-Media Carotídea , Criança , China , Diagnóstico Precoce , Feminino , Humanos , Masculino , Estudos Prospectivos , Análise de Onda de Pulso
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