Dataset Information

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

Similar Datasets

Project description:ImportanceExtremely low diastolic blood pressure has been reported to be associated with increased adverse cardiovascular events (ie, the diastolic J-shape phenomenon); however, current US guidelines recommend an intensive blood pressure target of less than 130/80 mm Hg without mentioning the lower limits of diastolic blood pressure.ObjectivesTo evaluate whether there is a diastolic J-shape phenomenon for patients with an treated systolic blood pressure of less than 130 mm Hg and to explore the safe and optimal diastolic blood pressure ranges for this patient population.Design, setting, and participantsThis cohort study analyzed outcome data of patients at high cardiovascular risk who were randomized to intensive or standard blood pressure control and achieved treated systolic blood pressure of less than 130 mm Hg in the Systolic Blood Pressure Intervention Trial (SPRINT) and Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial. Data were collected from October 2010 to August 2015 (SPRINT) and from September 1999 to June 2009 (ACCORD-BP). Data were analyzed from January to May 2020.ExposureTreated diastolic blood pressure, divided in intervals of less than 60, 60 to less than 70, 70 to less than 80, and 80 mm Hg and greater.Main outcomes and measuresThe primary outcome was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. A composite cardiovascular outcome, including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, was among the key secondary outcomes.ResultsA total of 7515 patients (mean [SD] age, 65.6 [8.7] years; 4553 [60.6%] men) were included in this analysis. The nominally lowest risk was observed at a diastolic blood pressure between 70 and 80 mm Hg for the primary outcome, the composite cardiovascular outcome, nonfatal myocardial infarction, and cardiovascular death. A mean diastolic blood pressure of less than 60 mm Hg was associated with significantly increased risk of the primary outcome (hazard ratio [HR], 1.46; 95% CI, 1.13-1.90; P = .004), the composite cardiovascular outcome (HR, 1.74; 95% CI, 1.26-2.41; P = .001), nonfatal myocardial infarction (HR, 1.73; 95% CI, 1.15-2.59; P = .008), and nonfatal stroke (HR, 2.67; 95% CI, 1.26-5.63; P = .01).Conclusions and relevanceThis cohort study found that lowering diastolic blood pressure to less than 60 mm Hg was associated with increased risk of cardiovascular events in patients with high cardiovascular risk and an treated systolic blood pressure less than 130 mm Hg. The finding that a diastolic blood pressure value between 70 and 80 mm Hg was an optimum target for this patient population merits further study.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets