A multi-omics study of circulating phospholipid markers of blood pressure

High-throughput techniques allow us to measure a wide-range of phospholipids which can provide insight into the mechanisms of hypertension. We aimed to conduct an in-depth multi-omics study of various phospholipids with systolic blood pressure (SBP) and diastolic blood pressure (DBP). The associations of blood pressure and 151 plasma phospholipids measured by electrospray ionization tandem mass spectrometry were performed by linear regression in five European cohorts (n = 2786 in discovery and n = 1185 in replication). We further explored the blood pressure-related phospholipids in Erasmus Rucphen Family (ERF) study by associating them with multiple cardiometabolic traits (linear regression) and predicting incident hypertension (Cox regression). Mendelian Randomization (MR) and phenome-wide association study (Phewas) were also explored to further investigate these association results. We identified six phosphatidylethanolamines (PE 38:3, PE 38:4, PE 38:6, PE 40:4, PE 40:5 and PE 40:6) and two phosphatidylcholines (PC 32:1 and PC 40:5) which together predicted incident hypertension with an area under the ROC curve (AUC) of 0.61. The identified eight phospholipids are strongly associated with triglycerides, obesity related traits (e.g. waist, waist-hip ratio, total fat percentage, body mass index, lipid-lowering medication, and leptin), diabetes related traits (e.g. glucose, insulin resistance and insulin) and prevalent type 2 diabetes. The genetic determinants of these phospholipids also associated with many lipoproteins, heart rate, pulse rate and blood cell counts. No significant association was identified by bi-directional MR approach. We identified eight blood pressure-related circulating phospholipids that have a predictive value for incident hypertension. Our cross-omics analyses show that phospholipid metabolites in the circulation may yield insight into blood pressure regulation and raise a number of testable hypothesis for future research.

Dried Blood Spot Biomarkers of Oxidative Stress and Inflammation Associated with Blood Pressure in Rural Senegalese Women with Incident Hypertension

Blood biomarkers of oxidative stress and inflammation have been associated with increased risk of hypertension development; yet their application in sub-Saharan Africa has been limited due to the lack of blood collection facilities. In this study, we evaluated the usefulness of dried blood spots (DBS), a more feasible alternative to venous blood, in rural sub-Saharan residents. We recruited 342 women with incident hypertension from rural Senegal, and measured C-reactive protein (CRP) and malondialdehyde (MDA) in DBS and concurrent blood pressure (BP) at baseline and 1-year follow-up. Associations of DBS biomarkers with current levels of and 1-year changes in BP were examined after adjusting for demographic, medical, and socioeconomic covariates. DBS concentrations of MDA were significantly associated with concurrent systolic BP (SBP) (p < 0.05), while DBS baseline concentrations of CRP were associated with longitudinal changes in SBP between baseline and follow-up. Compared to participants with baseline CRP < 1 mg/L, those with CRP of 1–3 mg/L and 3–10 mg/L had 2.11 mmHg (95%CI: −2.79 to 7.02 mmHg) and 4.68 mmHg (95%CI: 0.01 to 9.36 mmHg) increases in SBP at follow-up, respectively. The results support the use of DBS biomarkers for hypertension prevention and control, especially in settings with limited clinical resources.

Urinary Potassium Excretion, Fibroblast Growth Factor 23, and Incident Hypertension in the General Population-Based PREVEND Cohort

High plasma fibroblast growth factor 23 (FGF23) and low potassium intake have each been associated with incident hypertension. We recently demonstrated that potassium supplementation reduces FGF23 levels in pre-hypertensive individuals. The aim of the current study was to address whether 24-h urinary potassium excretion, reflecting dietary potassium intake, is associated with FGF23, and whether FGF23 mediates the association between urinary potassium excretion and incident hypertension in the general population. At baseline, 4194 community-dwelling individuals without hypertension were included. Mean urinary potassium excretion was 76 (23) mmol/24 h in men, and 64 (20) mmol/24 h in women. Plasma C-terminal FGF23 was 64.5 (54.2–77.8) RU/mL in men, and 70.3 (56.5–89.5) RU/mL in women. Urinary potassium excretion was inversely associated with FGF23, independent of age, sex, urinary sodium excretion, bone and mineral parameters, inflammation, and iron status (St. β −0.02, p < 0.05). The lowest sex-specific urinary potassium excretion tertile (HR 1.18 (95% CI 1.01–1.37)), and the highest sex-specific tertile of FGF23 (HR 1.17 (95% CI 1.01–1.37)) were each associated with incident hypertension, compared with the reference tertile. FGF23 did not mediate the association between urinary potassium excretion and incident hypertension. Increasing potassium intake, and reducing plasma FGF23 could be independent targets to reduce the risk of hypertension in the general population.

Common Carotid Artery Flow Parameters Predict the Incidence of Hypertension

The resistance index (RI) and pulsatility index (PI) in the common carotid artery (CCA) reflect vascular resistance and aortic stiffness. We investigated the association of these CCA flow parameters with the prevalence and incidence of hypertension, with comparison to the intima-media thickness (IMT). The cross-sectional analysis included 2660 participants who underwent carotid artery ultrasonography. Of those, 1249 normotensive participants at baseline were enrolled in the retrospective cohort analysis. A high RI, high PI, and increased IMT were indicated based on the optimal cutoff values in a receiver operating characteristic curve analysis. RI (β=0.158, P <0.001) and PI (β=0.130, P <0.001) were significantly associated with systolic blood pressure in the cross-sectional analysis. Over a mean 5.1-year follow-up period, 524 participants developed hypertension. A high RI (odds ratio [OR], 1.65; P <0.001), high PI (OR, 1.63; P <0.001), and increased IMT (OR, 1.40; P =0.017) were significant predicators for incident hypertension. Combining IMT and the PI, a high PI alone (OR, 1.52; P =0.008) was a significant predicator for incident hypertension, whereas increased IMT alone was not significantly associated with the risk of hypertension. The group with both increased IMT and a high PI had the highest risk of hypertension (OR, 2.24; P <0.001). Similar results were obtained from the analysis of IMT and RI, suggesting that CCA parameters evaluated by ultrasonography may help identify individuals at high risk of hypertension. In particular, CCA flow parameters are better predictors.

Hypertension incidence among middle-aged and older adults: findings from a 5-year prospective study in rural South Africa, 2010–2015

ObjectivesThere is a scarcity of longitudinal cohort studies in sub-Saharan Africa to understand the epidemiology of cardiovascular disease as a basis for intervention. We estimated incident hypertension and associated sociodemographic, health and behavioural risk factors in a population aged 40 years and older over a 5-year period.DesignWe assessed the association between incident hypertension and sociodemographic, health and behavioural factors using Poisson regression. We adjusted for non-response in 2015 using inverse probability sampling weights from a logistic regression including sex and age at baseline.SettingRural South Africa.ParticipantsWe used a population-based cohort of normotensive adults in 2010 who were aged 40 years and older at retest in 2015.ResultsOf 676 individuals completing baseline and 5-year follow-up, there were 193 incident cases of hypertension. The overall hypertension incidence rate was 8.374/100 person-years. In multivariable analyses, those who became hypertensive were more likely to be older, have a high waist circumference (incidence rate ratio (IRR): 1.557, 95% CI: 1.074 to 2.259) and be employed (IRR: 1.579, 95% CI: 1.071 to 2.329) at baseline. Being HIV positive and not on antiretroviral therapy at baseline was associated with lower risk of incident hypertension.ConclusionsOver a 5-year period, 29% of respondents developed hypertension. Given the high burden of hypertension in South Africa, continued longitudinal follow-up is needed to understand the complex interplay of non-communicable and infectious diseases and their underlying and modifiable risk factors to inform public health prevention strategies and programmes.

Associations of Dietary Patterns and Risk of Hypertension in Southwest China: A Prospective Cohort Study

Empirical data on the association between diet and incident hypertension in Southwest China is lacking. We examined the associations between various dietary patterns and the risk of incident hypertension in this prospective population cohort of Southwest China. A total of 5442 eligible adults were included from Guizhou Province, China, since 2010. Dietary information was obtained using face-to-face interviews with a semi-quantitative food frequency questionnaire, and dietary patterns were characterized using factor analysis. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated for the associations between various dietary patterns and incident hypertension risk using a Cox proportional hazard model. Until 2020, a total of 1177 new hypertension cases were identified during an average follow-up of 6.97 years. In the multivariable-adjusted analysis, a low intake of the junk food pattern was significantly associated with the reducing risk of incident hypertension (HR: 0.772, 95% CI: 0.671, 0.887) and a high intake of the vegetable–grain pattern statistically lowered the risk of incident hypertension (HR: 0.774, 95% CI: 0.669, 0.894) compared with the medium intake of such patterns. Higher adherence to the vegetable–grain pattern and lower adherence to the junk food pattern significantly lowered the hypertension incidence among the population in Southwest China. Those findings suggested healthy diet guidelines should be developed for the prevention of hypertension.

The role of different lipid measures for incident hypertension during more than 12 years follow-up: Tehran Lipid and Glucose Study

To examine the associations of different lipid measures and related indices with incident hypertension during a median follow-up of 12.89 years. Fasting levels of total cholesterol (TC), triglycerides (TG), high and low density lipoprotein cholesterol (HDL-C and LDL-C, respectively), and related indices (TC/HDL-C and TG/HDL-C) were determined in 7335 Iranian adults (men=3270) free of hypertension, aged 39.0 [standard deviation (SD):13.2] years. Multivariate Cox proportional hazard regression was applied and lipid parameters were considered either as categorical or continuous variables. During follow-up, 2413 (men=11260) participants experienced hypertension. Using the first quartile as reference, significant trends were found between quartiles of TG, HDL-C, TC/HDL-C, and TG/HDL-C in multivariate models; moreover considering these measures as continuous variables, a 1 SD increase in each of these parameters was significantly associated with risk of incident hypertension; the corresponding hazard ratios and confidence intervals were 1.06(1.02-1.10), 0.94(0.89-0.98), 1.04(1.01-1.09), and 1.04(1.01-1.07), respectively. The association between lipid measures and incident hypertension did not change after excluding lipid lowering drug users and those with type 2 diabetes mellitus and were independent of the baseline categories of blood pressure (P for interaction > 0.08). To take into account the nutrition data, a re-analysis on a subgroup (n=1705), showed that a 1-SD increase in TG and TG/HDL-C were associated with incident hypertension, after adjusting for dietary cofounders [1.15(1.08–1.24) and 1.03(1.01–1.04), respectively]. These findings indicate that TG, TG/HDL-C, and TC/HDL-C were independently associated with higher risk while HDL-C was associated with lower risk of incident hypertension.

A multi-ethnic polygenic risk score is associated with hypertension prevalence and progression throughout adulthood

Background: We used summary statistics from previously-published GWAS of systolic and diastolic BP and of hypertension to construct Polygenic Risk Scores (PRS) to predict hypertension across diverse populations. Methods: We used 10,314 participants of diverse ancestry from BioMe to train trait-specific PRS. We implemented a novel approach to select one of multiple potential PRS based on the same GWAS, by optimizing the coefficient of variation across estimated PRS effect sizes in independent subsets of the training dataset. We combined the 3 selected trait-specific PRS as their unweighted sum, called "PRSsum". We evaluated PRS associations in an independent dataset of 39,035 individuals from eight cohort studies, to select the final, multi-ethnic, HTN-PRS. We estimated its association with prevalent and incident hypertension 4-6 years later. We studied hypertension development within HTN-PRS strata in a longitudinal, six-visit, longitudinal dataset of 3,087 self-identified Black and White participants from the CARDIA study. Finally, we evaluated the HTN-PRS association with clinical outcomes in 40,201 individuals from the MGB Biobank. Results: Compared to other race/ethnic backgrounds, African-Americans had higher average values of the HTN-PRS. The HTN-PRS was associated with prevalent hypertension (OR=2.10, 95% CI [1.99, 2.21], per one standard deviation (SD) of the PRS) across all participants, and in each race/ethnic background, with heterogeneity by background (p-value < 1.0x10-4). The lowest estimated effect size was in African Americans (OR=1.53, 95% CI [1.38, 1.69]). The HTN-PRS was associated with new onset hypertension among individuals with normal (respectively, elevated) BP at baseline: OR=1.71, 95% CI [1.55, 1.91] (OR=1.48, 95% CI [1.27, 1.71]). Association was further observed in age-stratified analysis. In CARDIA, Black participants with high HTN-PRS percentiles developed hypertension earlier than White participants with high HTN-PRS percentiles. The HTN-PRS was significantly associated with increased risk of coronary artery disease (OR=1.12), ischemic stroke (OR=1.15), type 2 diabetes (OR=1.19), and chronic kidney disease (OR=1.12), in the MGB Biobank. Conclusions: The multi-ethnic HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up across adulthood and is associated with clinical outcomes.