Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Unravelling the Distinct Effects of Systolic and Diastolic Blood Pressure Using Mendelian Randomisation

ABSTRACT: A true discrepancy between the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on cardiovascular (CV) outcomes remains unclear. This study performed two-sample Mendelian randomization (MR) using genetic instruments that exclusively predict SBP, DBP or both to dissect the independent effect of SBP and DBP on a range of CV outcomes. Genetic predisposition to higher SBP and DBP was associated with increased risk of coronary artery disease (CAD), myocardial infarction (MI), stroke, heart failure (HF), atrial fibrillation (AF), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). Genetically proxied SBP exclusively was associated with CAD (OR 1.18, 95% CI: 1.03–1.36, per 10 mmHg), stroke (1.44[1.28–1.62]), ischemic stroke (1.49[1.30–1.69]), HF (1.41[1.20–1.65]), AF (1.28[1.15–1.43]), and T2DM (1.2[1.13–1.46]). Genetically proxied DBP exclusively was associated with stroke (1.21[1.06–1.37], per 5 mmHg), ischemic stroke (1.24[1.09–1.41]), stroke small-vessel (1.35[1.10–1.65]) and CAD (1.19[1.00–1.41]). Multivariable MR using exclusive SBP and DBP instruments showed the predominant effect of SBP on CAD (1.23[1.05–1.44], per 10 mmHg), stroke (1.39[1.20–1.60]), ischemic stroke (1.44[1.25–1.67]), HF (1.42[1.18–1.71]), AF (1.26[1.10–1.43]) and T2DM (1.31[1.14–1.52]). The discrepancy between effects of SBP and DBP on outcomes warrants further studies on underpinning mechanisms which may be amenable to therapeutic targeting.

SUBMITTER: Le N

PROVIDER: S-EPMC9323763 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

The total and direct effects of systolic and diastolic blood pressure on cardiovascular disease and longevity using Mendelian randomisation.

Project description:The 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guidelines lowered the hypertension threshold to ≥ 130/80 mmHg, but the role of diastolic BP remains contested. This two-sample mendelian randomisation study used replicated genetic variants predicting systolic and diastolic BP applied to the UK Biobank and large genetic consortia, including of cardiovascular diseases and parental lifespan, to obtain total and direct effects. Systolic and diastolic BP had positive total effects on CVD (odds ratio (OR) per standard deviation 2.15, 95% confidence interval (CI) 1.95, 2.37 and OR 1.91, 95% CI 1.73, 2.11, respectively). Direct effects were similar for systolic BP (OR 1.83, 95% CI 1.48, 2.25) but completely attenuated for diastolic BP (1.18, 95% CI 0.97, 1.44), although diastolic BP was associated with coronary artery disease (OR 1.24, 95% CI 1.03, 1.50). Systolic and diastolic BP had similarly negative total (- 0.20 parental attained age z-score, 95% CI - 0.22, - 0.17 and - 0.17, 95% CI - 0.20, - 0.15, respectively) and direct negative effects on longevity. Our findings suggest systolic BP has larger direct effects than diastolic BP on CVD, but both have negative effects (total and direct) on longevity, supporting the 2017 ACC/AHA guidelines lowering both BP targets.

| S-EPMC8575942 | biostudies-literature

Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses.

Project description:DISTINCT was an 8-week, double-blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) ?95 to <110 mm Hg. The current prespecified analysis compared BP reduction in participants with mild vs moderate baseline hypertension (ie, systolic [S]BP <160 mm Hg vs ?160 mm Hg and DBP <100 mm Hg vs ?100 mm Hg). A total of 1362 patients were analyzed by descriptive statistics. In all patient subgroups investigated, the NC combinations (ie, N: 20, 30, or 60 mg; C: 4, 8, 16, or 32 mg daily) provided greater SBP and DBP lowering and higher rates of BP control (defined as BP <140/90 mm Hg) than respective monotherapies or placebo, with greatest absolute BP reductions observed in the moderately elevated SBP or DBP subgroups. A trend to dose-response relationship was observed in each subgroup. In each SBP and DBP subgroup, treatment-related vasodilatory events (flushing, headache, or edema) were less frequent for patients receiving NC combination therapy than N monotherapy. These analyses support the use of calcium antagonist and angiotensin receptor blocker combination therapy in patients with both mild and moderate hypertension, for whom effective BP normalization and good drug tolerance would greatly reduce the risk of cardiovascular events.

| S-EPMC5111757 | biostudies-literature

Cardiac MR modelling of systolic and diastolic blood pressure.

Project description:AimsBlood pressure (BP) is a crucial factor in cardiovascular health and can affect cardiac imaging assessments. However, standard outpatient cardiovascular MR (CMR) imaging procedures do not typically include BP measurements prior to image acquisition. This study proposes that brachial systolic BP (SBP) and diastolic BP (DBP) can be modelled using patient characteristics and CMR data.MethodsIn this multicentre study, 57 patients from the PREFER-CMR registry and 163 patients from other registries were used as the derivation cohort. All subjects had their brachial SBP and DBP measured using a sphygmomanometer. Multivariate linear regression analysis was applied to predict brachial BP. The model was subsequently validated in a cohort of 169 healthy individuals.ResultsAge and left ventricular ejection fraction were associated with SBP. Aortic forward flow, body surface area and left ventricular mass index were associated with DBP. When applied to the validation cohort, the correlation coefficient between CMR-derived SBP and brachial SBP was (r=0.16, 95% CI 0.011 to 0.305, p=0.03), and CMR-derived DBP and brachial DBP was (r=0.27, 95% CI 0.122 to 0.403, p=0.0004). The area under the curve (AUC) for CMR-derived SBP to predict SBP>120 mmHg was 0.59, p=0.038. Moreover, CMR-derived DBP to predict DBP>80 mmHg had an AUC of 0.64, p=0.002.ConclusionCMR-derived SBP and DBP models can estimate brachial SBP and DBP. Such models may allow efficient prospective collection, as well as retrospective estimation of BP, which should be incorporated into assessments due to its critical effect on load-dependent parameters.

| S-EPMC10749049 | biostudies-literature

Effects of different statin types and dosages on systolic/diastolic blood pressure: Retrospective analysis of 24-hour ambulatory blood pressure database.

Project description:We previously demonstrated lower diastolic blood pressure (BP) levels under statin therapy in adult individuals who consecutively underwent 24-hour ambulatory BP monitoring and compared their levels to untreated outpatients. Here we evaluated systolic/diastolic BP levels according to different statin types and dosages. 987 patients (47.5% female, age 66.0 ± 10.1 years, BMI 27.7 ± 4.6 kg/m2 , clinic BP 146.9 ± 19.4/86.1 ± 12.1 mm Hg, 24-hour BP 129.2 ± 14.4/74.9 ± 9.2 mm Hg) were stratified into 4 groups: 291 (29.5%) on simvastatin 10-80 mg/d, 341 (34.5%) on atorvastatin 10-80 mg/d, 187 (18.9%) on rosuvastatin 5-40 mg/d, and 168 (17.0%) on other statins. There were no significant BP differences among patients treated by various statin types and dosages, except in lower clinic (P = .007) and daytime (P = .013) diastolic BP in patients treated with simvastatin and atorvastatin compared to other statins. Favorable effects of statins on systolic/diastolic BP levels seem to be independent of types or dosages, thus suggesting a potential class effect of these drugs.

| S-EPMC8030899 | biostudies-literature

Influence of Baseline Diastolic Blood Pressure on the Effects of Systolic Blood Pressure Lowering on Cognitive Function in Type 2 Diabetes Mellitus.

Project description:BackgroundLowering of systolic blood pressure (SBP) in patients with low diastolic blood pressure (DBP), can further lower DBP. This can potentially decrease cerebral perfusion and cognition. We examined the influence of baseline DBP on the effect of lowering SBP on cognition.MethodsThis is a post hoc analysis of the Memory in Diabetes (MIND) substudy (N = 1,430) of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (NCT00000620). Standard neuropsychological tests (Digit Symbol Substitution Test [DSST], Mini-Mental State Examination [MMSE], Rey Auditory Verbal Learning Test [RAVLT], and Stroop test) were performed at baseline and months 20 and 40. We compared the effects of intensive (goal SBP <120 mm Hg) vs. standard (goal SBP <140 mm Hg) SBP control on the changes in the 4 test scores from baseline to the averages of months 20 and 40 across the range of baseline DBP using cubic spline terms.ResultsMean age was 63 ± 6 years, 55% were women and 66% White. Participates with lower baseline DBP were older, had more cardiovascular events and a longer duration of diabetes. There was no difference in the change in DSST (-0.22; 95% CI -0.97, 0.52), MMSE (-0.14; 95% CI -0.34, 0.06), RAVLT (-0.12; 95% CI -0.29, 0.06), and Stroop interference (-0.47; 95% CI -1.76, 0.82) in the intensive vs. standard SBP intervention. There was no interaction between baseline DBP and change in scores with the SBP intervention.ConclusionsIntensive SBP reduction does not adversely affect cognition, even in those with low baseline DBP.

| S-EPMC9922945 | biostudies-literature

Dietary Influence on Systolic and Diastolic Blood Pressure in the TwinsUK Cohort.

Project description:Nutrition plays a key role in blood pressure (BP) regulation. Here, we examine associations between nutrient intakes and BP in a large predominantly female population-based cohort. We assessed the correlation between 45 nutrients (from food frequency questionnaires) and systolic BP/diastolic BP (SBP/DBP) in 3889 individuals from TwinsUK not on hypertensive treatments and replicated in an independent subset of monozygotic twins discordant for nutrient intake (17-242 pairs). Results from both analyses were meta-analysed. For significant nutrients, we calculated heritability using structural equation modelling. We identified and replicated 15 nutrients associated with SBP, 9 also being associated with DBP, adjusting for covariates and multiple testing. 14 of those had a heritable component (h2: 27.1-57.6%). Strong associations with SBP were observed for riboflavin (Beta(SE) = -1.49(0.38), P = 1.00 × 10-4) and tryptophan (-0.31(0.01), P = 5 × 10-4), while with DBP for alcohol (0.05(0.07), P = 1.00 × 10-4) and lactose (-0.05(0.0), P = 1.3 × 10-3). Two multivariable nutrient scores, combining independently SBP/DBP-associated nutrients, explained 22% of the variance in SBP and 13.6% of the variance in DBP. Moreover, bivariate heritability analysis suggested that nutrients and BP share some genetic influences. We confirm current understanding and extend the panel of dietary nutrients implicated in BP regulation underscoring the value of nutrient focused dietary research in preventing and managing hypertension.

| S-EPMC7400881 | biostudies-literature

Association of low diastolic blood pressure with all-cause death among US adults with normal systolic blood pressure.

Project description:Although the effect of intensive systolic blood pressure lowering is widely recognized, treatment-related low diastolic blood pressure still worrisome. This was a prospective cohort study based on the National Health and Nutrition Examination Survey. Adults (≥20 years old) with guideline-recommended blood pressure were included and pregnant women were excluded. Survey-weighted logistic regression and cox models were used for analysis. A total of 25 858 participants were included in this study. After weighted, the overall mean age of the participants was 43.17 (16.03) years, including 53.7% women and 68.1% non-Hispanic white. Numerous factors were associated with low DBP (<60 mmHg), including advanced age, heart failure, myocardial infarction, and diabetes. The use of antihypertensive drugs was also associated with lower DBP (OR, 1.52; 95% CI, 1.26-1.83). DBP of less than 60 mmHg were associated with a higher risk of all-cause death (HR, 1.30; 95% CI, 1.12-1.51) and cardiovascular death (HR, 1.34; 95% CI, 1.00-1.79) compared to those with DBP between 70 and 80 mmHg. After regrouping, DBP <60 mmHg (no antihypertensive drugs) was associated with a higher risk of all-cause death (HR, 1.46; 95% CI, 1.21-1.75). DBP <60 mmHg after taking antihypertensive drugs was not associated with a higher risk of all-cause death (HR, 0.99; 95% CI, 0.73-1.36). Antihypertensive drug is an important factor contributing to DBP below 60 mmHg. But the pre-existing risk does not increase further with an additional reduction of DBP after antihypertensive drugs treatment.

| S-EPMC10085810 | biostudies-literature

Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension.

Project description:BackgroundThe availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.MethodsWe conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.ResultsTwo blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P<5×10-8). Among them, a rare intergenic variant at novel locus, LOC100506274, was associated with lower systolic blood pressure in stage-1 (beta [SE]=-32.6 [6.0]; P=4.99×10-8) but not stage-2 analysis (P=0.11). Furthermore, a novel common variant at the known INSR locus was suggestively associated with diastolic blood pressure in stage-1 (beta [SE]=-0.36 [0.07]; P=4.18×10-7) and attained genome-wide significance in stage-2 (beta [SE]=-0.29 [0.03]; P=7.28×10-23). Nineteen additional signals suggestively associated with blood pressure in meta-analysis of single and aggregate rare variant findings (P<1×10-6 and P<1×10-4, respectively).DiscussionWe report one promising but unconfirmed rare variant for blood pressure and, more importantly, contribute insights for future blood pressure sequencing studies. Our findings suggest promise of aggregate analyses to complement single variant analysis strategies and the need for larger, diverse samples, and family studies to enable robust rare variant identification.

| S-EPMC9593435 | biostudies-literature

Bivariate genetic association analysis of systolic and diastolic blood pressure by copula models.

Project description:We conduct genetic association analysis in the subset of unrelated individuals from the San Antonio Family Studies pedigrees, applying a two-stage approach to take account of the dependence between systolic and diastolic blood pressure (SBP and DBP). In the first stage, we adjust blood pressure for the effects of age, sex, smoking, and use of antihypertensive medication based on a novel modification of censored regression. In the second stage, we model the bivariate distribution of the adjusted SBP and DBP phenotypes by a copula function with interpretable SBP-DBP correlation parameters. This allows us to identify genetic variants associated with each of the adjusted blood pressures, as well as variants that explain the association between the two phenotypes. Within this framework, we define a pleiotropic variant as one that reduces the SBP-DBP correlation. Our results for whole genome sequence variants in the gene ULK4 on chromosome 3 suggest that inference obtained from a copula model can be more informative than findings from the SBP-specific and DBP-specific univariate models alone.

| S-EPMC4143670 | biostudies-literature

Solar Activity Is Associated With Diastolic and Systolic Blood Pressure in Elderly Adults.

Project description:Background Since solar activity and related geomagnetic disturbances modulate autonomic nervous system activity, we hypothesized that these events would be associated with blood pressure (BP). Methods and Results We studied 675 elderly men from the Normative Aging Study (Boston, MA) with 1949 BP measurements between 2000 and 2017. Mixed-effects regression models were used to investigate the association of average 1-day (ie, day of BP measurement) to 28-day interplanetary magnetic field intensity, sunspot number, and a dichotomized measure of global geomagnetic activity (Kp index) in 4-day increments with diastolic and systolic BP. We adjusted for meteorological conditions and other covariates associated with BP, and in additional models adjusted for ambient air pollutants (particulate matter with an aerodynamic diameter ≤2.5 µm, black carbon, and particle number) and ambient particle radioactivity. There were positive associations between interplanetary magnetic field, sunspot number, and Kp index and BP that were greatest with these exposures averaged over 16 through 28 days before BP measurement. An interquartile range increase of 16-day interplanetary magnetic field and sunspot number and higher Kp index were associated with a 2.5 (95% CI, 1.7‒3.2), 2.8 (95% CI, 2.1‒3.4), and 1.7 (95% CI, 0.8‒2.5) mm Hg increase, respectively, for diastolic BP as well as a 2.1 (95% CI, 0.7‒3.6), 2.7 (95% CI, 1.5‒4.0), and 0.4 (95% CI, -1.2 to 2.1) mm Hg increase, respectively, for systolic BP. Associations remained after adjustment for ambient air pollutants and ambient particle radioactivity. Conclusions Solar activity and solar-driven geomagnetic disturbances were positively associated with BP, suggesting that these natural phenomena influence BP in elderly men.

| S-EPMC8751821 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data