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

Nhu Ngoc Le1, Tran Q B Tran1, Stefanie Lip1

  • 1Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK.

Genes
|July 27, 2022
PubMed

Insights

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) independently increase cardiovascular risks. SBP predominantly impacts coronary artery disease and stroke, while DBP also contributes to stroke risk, highlighting distinct therapeutic targets.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Epidemiology

Background:

  • The independent contributions of systolic blood pressure (SBP) and diastolic blood pressure (DBP) to cardiovascular (CV) outcomes are not fully understood.
  • Existing research presents a complex picture regarding the differential impact of SBP and DBP on various CV diseases.

Purpose of the Study:

  • To utilize two-sample Mendelian randomization (MR) to disentangle the independent effects of SBP and DBP on a spectrum of CV outcomes.
  • To identify specific cardiovascular diseases where SBP or DBP exert a predominant etiological influence.

Main Methods:

  • Employed two-sample Mendelian randomization (MR) analysis.
  • Utilized genetic instruments specifically predicting SBP, DBP, or both, to isolate their independent causal effects.
  • Assessed associations with multiple cardiovascular outcomes including coronary artery disease (CAD), myocardial infarction (MI), stroke, heart failure (HF), atrial fibrillation (AF), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM).

Main Results:

  • Both genetically predicted higher SBP and DBP were associated with increased risks of CAD, MI, stroke, HF, AF, CKD, and T2DM.
  • Exclusively SBP-associated genetic variants showed significant links to CAD, stroke (ischemic), HF, AF, and T2DM.
  • Exclusively DBP-associated genetic variants were linked to stroke (overall and ischemic), small vessel stroke, and CAD.
  • Multivariable MR confirmed the predominant effect of SBP on CAD, stroke, HF, AF, and T2DM, while DBP showed a distinct association with stroke subtypes.

Conclusions:

  • Systolic blood pressure has a more dominant role in the pathogenesis of major cardiovascular diseases, including CAD and stroke, compared to diastolic blood pressure.
  • Diastolic blood pressure also exerts an independent influence, particularly on specific stroke subtypes.
  • The distinct effects of SBP and DBP on cardiovascular outcomes suggest potential for targeted therapeutic strategies.

Keywords:
Mendelian randomizationblood pressurediastolicsystolic

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