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1.
PLoS One ; 19(5): e0301903, 2024.
Article En | MEDLINE | ID: mdl-38722884

INTRODUCTION: Hematology is an essential field for investigating the prognostic outcomes of cardiovascular diseases (CVDs). Recent research has suggested that mean corpuscular hemoglobin concentration (MCHC) is associated with a poor prognosis in several CVDs. There is no evidence of a correlation between MCHC and hypertension. Therefore, our study aimed to analyze the association of MCHC with all-cause and cardiovascular mortality in hypertensive patients. METHODS: We used cohort data from U.S. adults who participated in the National Health and Nutrition Examination Survey from 1999-2014. COX regression was applied to analyze the relationship between MCHC and all-cause and cardiovascular mortality. In addition, three models were adjusted to reduce confounding factors. We reanalyzed the data after propensity score matching (PSM) to inspect the stability of the results. Stratified analysis was additionally adopted to investigate the results of each subgroup. RESULTS: Our research included 15,154 individuals. During a mean follow-up period of 129 months, 30.6% of the hypertensive population succumbed to mortality. Based on previous studies, we categorized patients with MCHC ≤33mg/dl as the hypochromia group and those with >33mg/dl as the non-hypochromia group. After PSM, the hypochromia group had higher all-cause mortality (adjusted hazard ratio [HR]:1.26, 95% confidence interval [95%CI]:1.11-1.43) and cardiovascular mortality (adjusted HR:1.42, 95%CI:1.12-1.80) than the non-hypochromia group. The results of the COX regression remain stable after matching. Stratified analyses before PSM revealed an interaction of anemia in the relationship between MCHC and mortality, whereas there was no significant interaction after matching. CONCLUSION: In hypertensive individuals, low MCHC was correlated with a poor prognosis. Further studies on MCHC are necessary to analyze the potential mechanisms of its poor prognosis in hypertensive populations.


Erythrocyte Indices , Hemoglobins , Hypertension , Humans , Hypertension/blood , Hypertension/mortality , Male , Female , Middle Aged , Cohort Studies , Adult , Hemoglobins/analysis , Hemoglobins/metabolism , Aged , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Prognosis , Nutrition Surveys , Proportional Hazards Models
2.
Front Endocrinol (Lausanne) ; 15: 1373095, 2024.
Article En | MEDLINE | ID: mdl-38711984

Objective: The present study aimed to evaluate the association of plasma trans fatty acids (TFAs) biomarkers with the risk of hypertension. Methods: Using data from the National Health and Nutrition Examination Surveys (NHANES 2009-2010), we conducted a thorough analysis using both the traditional regression model and the Bayesian Kernel Machine Regression (BKMR) model to investigate the associations of individual TFAs and their mixtures with systolic blood pressure (SBP), diastolic blood pressure (DBP), and the risk of hypertension in a sample of 1,970 American adults. Results: The concentrations of TFAs were natural logarithms (ln) transformed to approximate a normal distribution. Multivariate linear regression models showed that each 1-unit increase in ln-transformed plasma concentrations of palmitelaidic, elaidic, vaccenic, and linolelaidic acids was associated with separate 2.94-, 3.60-, 2.46- and 4.78-mm Hg and 2.77-, 2.35-, 2.03-, and 3.70- mm Hg increase in SBP and DBP, respectively (P < 0.05). The BKMR model showed positive associations between the four TFAs mixtures and SBP and DBP. In addition, linolelaidic acid contributed the most to an increased blood pressure. Similar results were observed with the threshold of hypertension (≥130/80 mm Hg). Conclusion: Our findings provide preliminary evidence that plasma TFA concentrations are associated with increased blood pressure and the risk of hypertension in US adults. This study also suggests that linolelaidic acid might exhibit more deleterious effects on hypertension than other TFAs. Further studies should be conducted to validate these results.


Blood Pressure , Hypertension , Nutrition Surveys , Trans Fatty Acids , Humans , Hypertension/blood , Hypertension/epidemiology , Trans Fatty Acids/blood , Male , Female , Blood Pressure/physiology , Middle Aged , Adult , United States/epidemiology , Biomarkers/blood , Aged , Risk Factors
3.
J Hypertens ; 42(6): 1066-1074, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38690905

OBJECTIVE: The evidence regarding the associations of circulating metabolic biomarkers with hypertension risk is scarce. We aimed to examine the associations between circulating metabolites and risk of hypertension. METHODS: We included 49 422 individuals free of hypertension at baseline with a mean (SD) age of 53.5 (8.0) years from the UK Biobank. Nuclear magnetic resonance spectroscopy was used to quantify 143 individual metabolites. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% confidence intervals (CIs). RESULTS: During a mean (SD) follow-up of 11.2 (1.8) years, 2686 incident hypertension cases occurred. Out of 143 metabolites, 76 were associated with incident hypertension, among which phenylalanine (hazard ratio: 1.40; 95% CI: 1.24-1.58) and apolipoprotein A1 (hazard ratio: 0.76; 95% CI: 0.66-0.87) had the strongest association when comparing the highest to the lowest quintile. In general, very-low-density lipoprotein (VLDL) particles were positively, whereas high-density lipoprotein (HDL) particles were inversely associated with risk of hypertension. Similar patterns of cholesterol, phospholipids, and total lipids within VLDL and HDL particles were observed. Triglycerides within all lipoproteins were positively associated with hypertension risk. Other metabolites showed significant associations with risk of hypertension included amino acids, fatty acids, ketone bodies, fluid balance and inflammation markers. Adding 10 selected metabolic biomarkers to the traditional hypertension risk model modestly improved discrimination (C-statistic from 0.745 to 0.752, P < 0.001) for prediction of 10-year hypertension incidence. CONCLUSION: Among UK adults, disturbances in metabolic biomarkers are associated with incident hypertension. Comprehensive metabolomic profiling may provide potential novel biomarkers to identify high-risk individuals.


Biological Specimen Banks , Biomarkers , Hypertension , Humans , Hypertension/blood , Hypertension/epidemiology , United Kingdom/epidemiology , Middle Aged , Biomarkers/blood , Male , Female , Adult , Risk Factors , Aged , UK Biobank
4.
J Hypertens ; 42(6): 1101-1104, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38690908

Isolated nocturnal hypertension (INHT), defined as nighttime elevated blood pressure (BP) with normal daytime BP assessed by ambulatory BP monitoring, is associated with higher cardiovascular morbidity and mortality. We hypothesized that an alteration in the circulating renin-angiotensin system (RAS) contributes to INHT development. We examined circulating levels of angiotensin (Ang) (1-7) and Ang II and ACE2 activity in 26 patients that met the INHT criteria, out of 50 that were referred for BP evaluation (62% women, 45 ±â€Š16 years old). Those with INHT were older, had a higher BMI, lower circulating Ang-(1-7) (P = 0.002) and Ang II levels (P = 0.02) and no change in ACE2 activity compared to those normotensives. Nighttime DBP was significantly correlated with Ang-(1-7) and Ang II levels. Logistic regression showed significant association in Ang-(1-7) and Ang II levels with INHT. Our study reveals differences in circulating RAS in individuals with INHT.


Angiotensin II , Angiotensin I , Hypertension , Peptide Fragments , Humans , Angiotensin I/blood , Female , Male , Middle Aged , Peptide Fragments/blood , Hypertension/blood , Hypertension/physiopathology , Adult , Angiotensin II/blood , Renin-Angiotensin System/physiology , Circadian Rhythm , Blood Pressure , Angiotensin-Converting Enzyme 2/blood , Blood Pressure Monitoring, Ambulatory , Peptidyl-Dipeptidase A/blood
5.
Arch Endocrinol Metab ; 68: e230301, 2024 May 10.
Article En | MEDLINE | ID: mdl-38739525

Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.


Hypertension , Thyrotropin , Thyroxine , Triiodothyronine , Humans , Hypertension/epidemiology , Hypertension/blood , Male , Female , Brazil/epidemiology , Middle Aged , Prospective Studies , Longitudinal Studies , Adult , Thyrotropin/blood , Incidence , Thyroxine/blood , Triiodothyronine/blood , Hyperthyroidism/blood , Hyperthyroidism/epidemiology , Hypothyroidism/blood , Hypothyroidism/epidemiology , Risk Factors , Thyroid Function Tests , Aged
6.
Cardiovasc Diabetol ; 23(1): 141, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38664804

BACKGROUND: Non-insulin-based insulin resistance (NI-IR) indices have been reported to have an association with prevalent hypertension, however, no cohort studies to date have compared their prediction of hypertension among young adults. METHODS: A total of 2,448 military men and women, aged 18-39 years, without baseline hypertension in Taiwan were followed for incident hypertension events from 2014 until the end of 2020. All subjects underwent annual health examinations including measurements of blood pressure (BP) in mmHg. Systolic BP (SBP) 130-139/diastolic BP (DBP) < 80, SBP < 130/DBP 80-89, and SBP 130-139/DBP 80-89 were respectively defined as stage I isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and combined hypertension (CH). The cut-off levels of stage II hypertension for SBP and DBP were 140-159 and 90-99, respectively. Four NI-IR indices included the ratio of serum triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C), TyG index defined as ln[TG* fasting glucose (FG)/2], Metabolic Score for IR (METS-IR) defined as ln[(2* FG) + TG)* body mass index (BMI)/(ln(HDL-C))], and ZJU index defined as BMI + FG + TG + 3* alanine transaminase/aspartate transaminase (+ 2 if female). Multivariable Cox regression analysis was performed with adjustments for baseline age, sex, body mass index, BP, substance use, family history for early onset cardiovascular diseases or hypertension, low-density lipoprotein cholesterol, kidney function, serum uric acid and physical activity to determine the associations. RESULTS: During a median follow-up of 6.0 years, there were 920 hypertension events (37.6%). Greater TyG, TG/HDL-C and METS-IR indices were associated with a higher risk of stage I IDH (hazard ratios (HRs) and 95% confidence intervals: 1.376 (1.123-1.687), 1.082 (1.039-1.127) and 3.455 (1.921-6.214), respectively), whereas only greater ZJU index was associated with a higher risk of stage II IDH [HRs: 1.011 (1.001-1.021)]. In addition, greater ZJU index was associated with a higher risk of stage II ISH [HR: 1.013 (1.003-1.023)], and greater TyG index was associated with a higher risk of stage II CH [HR: 2.821 (1.244-6.395)]. CONCLUSION: Insulin resistance assessed by various NI-IR indices was associated with a higher risk of hypertension in young adults, while the assessment ability for specific hypertension category may differ by NI-IR indices.


Biomarkers , Blood Glucose , Blood Pressure , Hypertension , Insulin Resistance , Military Personnel , Humans , Male , Female , Hypertension/diagnosis , Hypertension/physiopathology , Hypertension/epidemiology , Hypertension/blood , Young Adult , Adolescent , Adult , Risk Assessment , Risk Factors , Biomarkers/blood , Taiwan/epidemiology , Blood Glucose/metabolism , Time Factors , Incidence , Predictive Value of Tests , Age Factors , Military Health , Triglycerides/blood , Prognosis
7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 52(4): 413-419, 2024 Apr 24.
Article Zh | MEDLINE | ID: mdl-38644257

Objective: To explore the relationship between the triglyceride glucose (TyG) index and the risk of developing hypertension among rural Chinese adults. Methods: A prospective cohort study was conducted from 2007 to 2008, involving 20 194 adults selected through random cluster sampling from a rural community in Luoyang City, Henan Province. Follow-ups were carried out in 2013-2014 and 2018-2020. After excluding participants with hypertension at baseline, those with missing TyG index data, individuals who passed away during follow-up, and those with incomplete hypertension status at the second visit, 9 802 participants were included in the analysis. Baseline and follow-up assessments included questionnaire interviews, physical measurements (including blood pressure), and blood sample collection for fasting lipid and glucose levels. Participants were divided into four groups according to TyG index quartiles, and a modified Poisson regression model was utilized to assess the association between TyG index quartiles and hypertension risk. Results: The study cohort comprised 9 802 participants with a median age of 48 (39, 57) years, including 3 803 males (38.80%). Participants were distributed across TyG index quartiles as follows: TyG<8.2 group (2 224 individuals), TyG 8.2-8.5 group (2 653 individuals), TyG 8.6-8.9 (2 441 individuals), and TyG≥9.0 (2 484 individuals). Over a follow-up period of (11.1±1.3) years, 3 378 subjects developed hypertension, resulting in a cumulative incidence of 34.46% (3 378/9 802). The risk of hypertension increased with higher TyG index quartiles (Ptrend<0.05). Compared to the TyG<8.2, the TyG 8.2-8.5 (RR=1.11, 95%CI 1.01-1.22, P=0.023), TyG 8.6-8.9 (RR=1.16, 95%CI 1.06-1.27, P=0.023), and TyG≥9.0 (RR=1.20, 95%CI 1.10-1.31, P=0.023) exhibited increased hypertension risk after adjusting for age, gender, educational level, and other potential confounders. Subgroup analyses based on gender and age at baseline yielded results consistent with the main analysis. Conclusions: The TyG index is positively correlated with the risk of developing hypertension in the rural adult population.


Blood Glucose , Hypertension , Rural Population , Triglycerides , Humans , Hypertension/epidemiology , Hypertension/blood , Prospective Studies , Middle Aged , Male , Triglycerides/blood , Adult , Female , Risk Factors , Blood Glucose/analysis , Rural Population/statistics & numerical data , China/epidemiology , Incidence , Cohort Studies , Blood Pressure
8.
Nat Commun ; 15(1): 3441, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38658550

Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancestry genome-wide association meta-analysis of 1,029,323 individuals and ancestry-specific meta-analysis identifies a total of 351 loci, including 17 previously unreported loci. The genetic architecture of serum urate control is similar between European and East Asian populations. A transcriptome-wide association study, enrichment analysis, and colocalization analysis in relevant tissues identify candidate serum urate-associated genes, including CTBP1, SKIV2L, and WWP2. A phenome-wide association study using polygenic risk scores identifies serum urate-correlated diseases including heart failure and hypertension. Mendelian randomization and mediation analyses show that serum urate-associated genes might have a causal relationship with serum urate-correlated diseases via mediation effects. This study elucidates our understanding of the genetic architecture of serum urate control.


Genome-Wide Association Study , Hyperuricemia , Uric Acid , Humans , DNA-Binding Proteins/genetics , Genetic Predisposition to Disease , Gout/genetics , Gout/blood , Heart Failure/genetics , Heart Failure/blood , Hypertension/genetics , Hypertension/blood , Hyperuricemia/genetics , Hyperuricemia/blood , Mendelian Randomization Analysis , Multifactorial Inheritance , Polymorphism, Single Nucleotide , Transcriptome , Uric Acid/blood
9.
Cardiovasc Diabetol ; 23(1): 135, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38658924

BACKGROUND: The triglyceride-glucose (TyG) index and blood pressure (BP) are correlated and serve as risk factors for cardiovascular disease (CVD). The potential impact of BP status on the association between the TyG index and CVD risk remains uncertain. This study aims to investigate the relationships between the TyG index and incident CVD in Chinese middle-aged and elderly adults, considering variations in BP status among participants. METHODS: 6558 participants (mean age: 58.3 (± 8.7) years; 46.0% were men) without prevalent CVD were recruited from the China Health and Retirement Longitudinal Study. Participants were divided into three groups according to their systolic blood pressure (SBP) levels (< 120mmHg, 120 ∼ 129mmHg, ≥ 130mmHg). The TyG index was computed as ln[triglyceride (mg/dl) * fasting blood glucose (mg/dl)/2]. The primary outcome was CVD (heart disease and stroke), and the secondary outcomes were individual CVD components. Cox regression models and restricted cubic splines were performed to investigate the associations between continuous and categorical TyG with CVD. RESULTS: 1599 cases of CVD were captured during 58,333 person-years of follow-up. Per 1-SD higher TyG index was associated with a 19% (HR: 1.19; 95% CI: 1.12, 1.27) higher risk for incident CVD, and the participants with the highest quartile of TyG index had a 54% (HR: 1.54; 95% CI: 1.29, 1.84) higher risk of CVD compared to those in the lowest quartile. SBP significantly modifies the association between the TyG index and CVD, with higher HRs for CVD observed in those with optimal and normal SBP. SBP partially mediated the associations between the TyG index with CVD. The results were generally consistent among participants with varying pulse pressure statuses rather than diastolic BP statuses. CONCLUSIONS: The associations between the TyG index and CVD were modified by BP status, with greater HRs for CVD observed among those who had SBP < 130mmHg. SBP can partially mediate the association between the TyG index with CVD, highlighting the importance of early screening for the TyG index to identify at risk of hypertension and CVD.


Biomarkers , Blood Glucose , Blood Pressure , Cardiovascular Diseases , Triglycerides , Humans , Male , Female , China/epidemiology , Middle Aged , Triglycerides/blood , Blood Glucose/metabolism , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/blood , Cardiovascular Diseases/physiopathology , Incidence , Aged , Risk Assessment , Biomarkers/blood , Longitudinal Studies , Time Factors , Hypertension/epidemiology , Hypertension/diagnosis , Hypertension/blood , Hypertension/physiopathology , Prognosis , Risk Factors , Heart Disease Risk Factors , Systole
10.
Clin Biochem ; 127-128: 110766, 2024 May.
Article En | MEDLINE | ID: mdl-38679273

BACKGROUND: Sirtuin 7 (SIRT7), as a nicotinamide adenine dinucleotide-dependent protein/histone deacetylase, has been implicated in the pathogenesis of cardiovascular diseases. However, whether SIRT7 is related to hypertension remains largely unclear. Thus, this study aims to explore the effects and correlation between SIRT7 and hypertension. METHODS: A total of 72 patients with essential hypertension and 82 controls with non-hypertension were recruited at Beijing Tongren Hospital Affiliated with Capital Medical University from July 2022 to June 2023. Plasma SIRT7 expression was measured using enzyme-linked immunosorbent assay analysis. Clinical baseline characteristics, laboratory measurements, echocardiographic data, and medical therapy were collected. RESULTS: Plasma levels of SIRT7 were lower in hypertensive patients compared with non-hypertensive patients [0.97 (0.58-1.30) vs. 1.24 (0.99-1.46) ng/mL, P < 0.001, respectively]. Furthermore, compared with the low SIRT7 group, there were lower levels of systolic blood pressure, hyperlipidemia, and the ultrasonic electrocardiogram parameters left ventricular end-diastolic diameter and left atrial in diastole in the high SIRT7 group (P < 0.05, respectively). More importantly, multivariate logistic regression analyses indicated that plasma SIRT7 was a predictor of hypertension [OR: 0.06, 95 % CI (0.02-0.19), P < 0.001]. Receiver operating characteristics curve analysis revealed that the optimal cutoff value for plasma SIRT7 levels in detecting hypertension was determined as 0.85 ng/mL with a sensitivity of 73.6 % and a specificity of 89.0 %. The area under the curve for SIRT7 was 0.821 (95 % CI, 0.751-0.878; P < 0.001). CONCLUSION: Plasma levels of SIRT7 are decreased in patients with essential hypertension, implying its potential as a biomarker for diagnosing essential hypertension..


Essential Hypertension , Sirtuins , Humans , Female , Male , Middle Aged , Essential Hypertension/blood , Sirtuins/blood , Adult , Aged , Biomarkers/blood , Case-Control Studies , ROC Curve , Hypertension/blood
11.
Pediatr Obes ; 19(6): e13112, 2024 Jun.
Article En | MEDLINE | ID: mdl-38439600

INTRODUCTION: Prevalence and risk factors for elevated glycated haemoglobin (HbA1c) and blood pressure (BP) are poorly understood among Pacific children. We examined associations of HbA1c and BP in 6-9 year-olds with body mass index (BMI) at ages 2, 5, and BMI velocity between 2-9 years in Samoa. METHODS: HbA1c (capillary blood) and BP were measured in n = 410 Samoan children who were part of an ongoing cohort study. Multilevel models predicted BMI trajectory characteristics. Generalized linear regressions assessed associations of childhood characteristics and BMI trajectories with HbA1c and BP treated as both continuous and categorical outcomes. Primary caregiver-reported childhood characteristics were used as covariates. RESULTS: Overall, 12.90% (n = 53) of children had high HbA1c (≥5.7%) and 33.17% (n = 136) had elevated BP. BMI at 5-years and BMI velocity were positively associated with high HbA1c prevalence in males. A 1 kg/m2 per year higher velocity was associated with a 1.71 (95% CI: 1.07, 2.75) times higher prevalence of high HbA1c. In females, higher BMI at 5-years and greater BMI velocity were associated with higher BP at 6-9 years (95% CI: 1.12, 1.40, and 1.42, 2.74, respectively). CONCLUSION: Monitoring childhood BMI trajectories may inform cardiometabolic disease screening and prevention efforts in this at-risk population.


Blood Pressure , Body Mass Index , Glycated Hemoglobin , Humans , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Male , Female , Child , Samoa/epidemiology , Pediatric Obesity/epidemiology , Pediatric Obesity/blood , Prevalence , Risk Factors , Hypertension/epidemiology , Hypertension/blood , Child, Preschool , Cohort Studies
12.
Nature ; 628(8006): 130-138, 2024 Apr.
Article En | MEDLINE | ID: mdl-38448586

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1-7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8-11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.


Biomarkers , Genome-Wide Association Study , Metabolomics , Female , Humans , Pregnancy , Acetone/blood , Acetone/metabolism , Biomarkers/blood , Biomarkers/metabolism , Cholestasis, Intrahepatic/blood , Cholestasis, Intrahepatic/genetics , Cholestasis, Intrahepatic/metabolism , Cohort Studies , Genome-Wide Association Study/methods , Hypertension/blood , Hypertension/genetics , Hypertension/metabolism , Lipoproteins/genetics , Lipoproteins/metabolism , Magnetic Resonance Spectroscopy , Mendelian Randomization Analysis , Metabolic Networks and Pathways/genetics , Phenotype , Polymorphism, Single Nucleotide/genetics , Pregnancy Complications/blood , Pregnancy Complications/genetics , Pregnancy Complications/metabolism
14.
Hypertens Res ; 47(5): 1362-1371, 2024 May.
Article En | MEDLINE | ID: mdl-38454147

The measurement evolution enabled more accurate evaluation of aldosterone production in hypertensive patients. However, the cut-off values for novel assays have been not sufficiently validated. The present study was undertaken to validate the novel chemiluminescent enzyme immunoassay for aldosterone in conjunction with other methods. Moreover, we also aimed to establish a new cut-off value for primary aldosteronism in the captopril challenge test using the novel assay. First, we collected 390 plasma samples, in which aldosterone levels measured using liquid chromatography-mass spectrometry ranged between 0.18 and 1346 ng/dL. The novel chemiluminescent enzyme immunoassay showed identical correlation of plasma aldosterone with liquid chromatography-mass spectrometry, in contrast to conventional radioimmunoassay. Further, we enrolled 299 and 39 patients with primary aldosteronism and essential hypertension, respectively. Plasma aldosterone concentrations measured using the novel assay were lower than those measured by radioimmunoassay, which resulted in decreased aldosterone-to-renin ratios. Subsequently, positive results of the captopril challenge test based on radioimmunoassay turned into "negative" based on the novel assay in 45% patients with primary aldosteronism, using the conventional cut-off value (aldosterone-to-renin activity ratio > 20 ng/dL per ng/mL/h). Receiver operating characteristic curve analysis demonstrated that aldosterone-to-renin activity ratios > 8.2 ng/dL per ng/mL/h in the novel assay was compatible with the conventional diagnosis (sensitivity, 0.874; specificity, 0.980). Our study indicates the great measurement accuracy of the novel chemiluminescent enzyme immunoassay for aldosterone, and the importance of measurement-adjusted cut-offs in the diagnosis of primary aldosteronism.


Aldosterone , Captopril , Hyperaldosteronism , Luminescent Measurements , Humans , Hyperaldosteronism/diagnosis , Hyperaldosteronism/blood , Male , Female , Middle Aged , Aldosterone/blood , Retrospective Studies , Adult , Aged , Luminescent Measurements/methods , Immunoenzyme Techniques/methods , Hypertension/blood , Hypertension/diagnosis , Renin/blood , Cohort Studies , Radioimmunoassay
15.
Wien Med Wochenschr ; 174(7-8): 161-172, 2024 May.
Article En | MEDLINE | ID: mdl-38451351

BACKGROUND: This study aimed to evaluate plasma relaxin­2 (RLN-2) levels in patients with arterial hypertension (AH) and their relationships with clinical and laboratory parameters. METHODS: The study involved 106 hypertensive patients, including 55 with type 2 diabetes mellitus (T2DM), and 30 control subjects. Plasma RLN-2 levels were measured using an enzyme-linked immunosorbent assay kit. RESULTS: RLN-2 levels were reduced in patients with AH compared to healthy volunteers (p < 0.001), and hypertensive patients with T2DM had lower RLN-2 levels than those without impaired glucose metabolism (p < 0.001). RLN­2 was negatively correlated with systolic blood pressure (SBP) (p < 0.001) and anthropometric parameters such as body mass index (BMI; p = 0.027), neck (p = 0.045) and waist (p = 0.003) circumferences, and waist-to-hip ratio (p = 0.011). RLN­2 also had inverse associations with uric acid levels (p = 0.019) and lipid profile parameters, particularly triglycerides (p < 0.001) and non-HDL-C/HDL­C (p < 0.001), and a positive relationship with HDL­C (p < 0.001). RLN­2 was negatively associated with glucose (p < 0.001), insulin (p = 0.043), HbA1c (p < 0.001), and HOMA-IR index (p < 0.001). Univariate binary logistic regression identified RLN­2 as a significant predictor of impaired glucose metabolism (p < 0.001). CONCLUSIONS: Decreased RLN-2 levels in patients with AH and T2DM and established relationships of RLN­2 with SBP and parameters of glucose metabolism and lipid profile suggest a diagnostic role of RLN­2 as a biomarker for AH with T2DM.


Diabetes Mellitus, Type 2 , Hypertension , Relaxin , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Male , Female , Middle Aged , Relaxin/blood , Hypertension/blood , Hypertension/diagnosis , Aged , Adult , Reference Values , Statistics as Topic , Body Mass Index , Biomarkers/blood
16.
Heart Vessels ; 39(6): 563-570, 2024 Jun.
Article En | MEDLINE | ID: mdl-38381171

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case-control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor-CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29-16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23-7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01-1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07-0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05-0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD.


Biomarkers , Cardiovascular Diseases , Follistatin-Related Proteins , Aged , Female , Humans , Male , Middle Aged , Aryldialkylphosphatase/blood , Biomarkers/blood , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/blood , Case-Control Studies , Follistatin-Related Proteins/blood , Hypertension/epidemiology , Hypertension/blood , Hypertension/diagnosis , Mexico/epidemiology , Risk Assessment/methods , Risk Factors
17.
Medicine (Baltimore) ; 103(1): e36784, 2024 Jan 05.
Article En | MEDLINE | ID: mdl-38181288

BACKGROUND: The gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) has recently been recognized to be one of the risk factors for cardiovascular disease (CVD). However, there is a scarcity of data on the relationship between circulating TMAO levels and hypertension in patients with CVD. Meta analysis and a dose-response relationship were used in this study to assess the relationship between circulating trimethylamine N-oxide levels and the risk of hypertension in patients with CVD. METHODS: CNKI, Wanfang Database, Pubmed, Embase, Cochrane Library, and Web of Science were searched up to June 01, 2023. Meta-analysis and dose-response analysis of relative risk data from prospective cohort studies reporting on the relationship between circulating TMAO levels and hypertension risk in patients with CVD were conducted. RESULTS: Fifteen studies with a total of 15,498 patients were included in the present meta-analysis. Compared with a lower circulating TMAO level, a higher TMAO level was associated with a higher risk of hypertension in patients with CVD (RR = 1.14,95%CI (1.08, 1.20)). And the higher the TMAO level, the greater the risk of hypertension. The dose-response analysis revealed a linear dose-response relationship between circulating TMAO levels and the risk of hypertension in patients with CVD. The risk of hypertension increased by 1.014% when the circulating TMAO level increased by 1 µ mol/L. CONCLUSION: In patients with CVD, the level of circulating TMAO is significantly related to the risk of hypertension. The risk of hypertension increased by 1.014% for every 1 µ mol/L increase in circulating TMAO levels.


Cardiovascular Diseases , Hypertension , Methylamines , Humans , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Hypertension/blood , Hypertension/epidemiology , Methylamines/blood , Prospective Studies
18.
Hypertens Res ; 47(5): 1120-1132, 2024 May.
Article En | MEDLINE | ID: mdl-38129667

The association between uric acid (UA) and hyperuricemia with 5-year hypertension incidence using different blood pressure (BP) diagnostic references in men and women without cardiometabolic diseases is unknown. We used the checkup data from Kagoshima Kouseiren Hospital. All participants with hypertension or on BP medication, diabetes, dyslipidemia, obesity, estimated glomerular filtration rate<60 ml/min/1.73m2, metabolic syndrome, history of gout, and UA-lowering medication were excluded. UA was categorized into sex-specific quartiles and hyperuricemia was defined as UA > 7 mg/dl in men and UA > 6 mg/dl in women. We performed multivariate logistic regression to assess the effects of UA on hypertension development. The 5-year hypertension incidence was defined as subsets of BP ≥ 140/90 mmHg in cohort 1 and BP ≥ 130/80 mmHg in cohort 2. The study enrolled 21,443 participants (39.8%, men) in cohort 1 and 15,245 participants (36.5%, men) in cohort 2. The incidence of hypertension in cohorts 1 and 2 over 5 years was 16.3% and 29.7% in men and 10.9% and 21.4% in women, respectively. When comparing the fourth to the first UA quartile, there was an association with hypertension in men in cohort 1, with odds ratio (OR): 1.36 (95% confidence interval [CI], 1.13-1.63, p < 0.01) and cohort 2, OR: 1.31 (95%CI, 1.09-1.57, p < 0.01), respectively, but not in women. Additionally, an association between hyperuricemia and hypertension was observed in men only in cohort 1, with OR: 1.23 (95%CI, 1.07-1.42, p = 0.02), and in women in cohort 2, OR: 1.57 (95%CI, 1.14-2.16, p < 0.01). The effect of UA on the development of hypertension is influenced by sex and incidence differs with the BP reference used. Uric acid effect on the development of hypertension is affected by sex and incidence differs with the BP reference used.


Blood Pressure , Hypertension , Hyperuricemia , Uric Acid , Humans , Hypertension/blood , Hypertension/epidemiology , Hypertension/diagnosis , Female , Male , Uric Acid/blood , Middle Aged , Aged , Hyperuricemia/blood , Hyperuricemia/epidemiology , Blood Pressure/physiology , Adult , Reference Values , Sex Factors , Incidence , Risk Factors , Cohort Studies , Sex Characteristics
19.
N Engl J Med ; 389(18): 1685-1692, 2023 Nov 02.
Article En | MEDLINE | ID: mdl-37913506

Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in CORIN, the gene encoding atrial natriuretic peptide (ANP)-converting enzyme. A plasma sample obtained from one of the siblings had no detectable levels of corin or N-terminal pro-ANP but had elevated levels of B-type natriuretic peptide (BNP) and one of the two protein markers of fibrosis that we tested. These and other findings support the hypothesis that BNP cannot fully compensate for a lack of activation of the ANP pathway and that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis.


Arrhythmias, Cardiac , Cardiomyopathies , Heart Atria , Hypertension , Humans , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/genetics , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/pathology , Atrial Fibrillation , Atrial Natriuretic Factor/blood , Atrial Natriuretic Factor/genetics , Atrial Natriuretic Factor/metabolism , Cardiomyopathies/blood , Cardiomyopathies/diagnosis , Cardiomyopathies/genetics , Cardiomyopathies/metabolism , Fibrosis , Heart Atria/diagnostic imaging , Heart Atria/metabolism , Heart Atria/pathology , Hypertension/blood , Hypertension/genetics , Hypertension/metabolism , Natriuretic Peptide, Brain/blood , Natriuretic Peptide, Brain/genetics , Natriuretic Peptide, Brain/metabolism , Serine Endopeptidases/blood , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Siblings
20.
J Clin Hypertens (Greenwich) ; 25(10): 951-956, 2023 10.
Article En | MEDLINE | ID: mdl-37688309

Elevated triglyceride glucose (TyG) index is associated with an increased risk of cardiovascular disease. The current study aimed to investigate whether the TyG index was correlated with renal function decline in patients with hypertension. Han Chinese participants with essential hypertension were included. The TyG index was calculated as ln[fasting triglycerides (mg/dL) * fasting glucose (mg/dL)/2]. Renal function decline was defined as >25% decline in estimated glomerular filtration rate (eGFR). The Cox proportional hazard regression model was used to examine the independent effect of the TyG index on renal events. In total, 548 Han Chinese hypertensive participants with a mean age of 62.1 ± 14.3 years were eligible for enrollment. During a mean follow-up period of 4.7 ± 3.1 years, 97 patients suffered from >25% decline in eGFR. When compared to those without eGFR decline, patients with eGFR decline had higher fasting triglyceride levels (P = .056), fasting glucose levels (P = .014), and TyG indexes (P = .014). The Cox proportional hazard regression model revealed that the TyG index (hazard ratio [HR] = 1.490; 95% confidence interval [CI] = 1.016-2.185, P = .041), office systolic blood pressure (HR = 1.013; 95% CI = 1.000-1.026, P = .047), diabetes mellitus (HR = 1.797, 95% CI = 1.026-3.147, P = .040), and baseline eGFR (HR = 1.015; 95% CI = 1.002-1.028, P = .025) were associated with renal events. In conclusions, an elevated TyG index is independently associated with an increased risk of eGFR decline in hypertensive patients.


Blood Glucose , Hypertension , Triglycerides , Aged , Humans , Middle Aged , Biomarkers/blood , Blood Glucose/analysis , East Asian People , Glucose , Hypertension/blood , Hypertension/complications , Hypertension/epidemiology , Hypertension/ethnology , Kidney/physiology , Risk Assessment , Risk Factors , Triglycerides/blood
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