Clinical Effect of Naturally Random Allocation to Lower Systolic Blood Pressure Beginning Before the Development of Hypertension
Open accessAbstract
Systolic blood pressure (SBP) rises approximately linearly with age in most societies. The cause of this rise is unclear. We tested the hypothesis that SBP is causally associated with the rate of rise in SBP with age by evaluating the effect of 12 polymorphisms associated with lower SBP on the age-related rate of rise in SBP in a series of meta-regression analyses involving ≤199 477 participants in 63 studies. We then evaluated the effect of these polymorphisms on the odds of coronary heart disease in 22 223 case and 64 762 control subjects and compared it with the effect of lower SBP observed in both prospective cohort studies and blood pressure–lowering randomized trials. All 12 polymorphisms were associated with both lower SBP and a slower age-related rise in SBP. The weighted mean effect of these 12 polymorphisms was associated with a 0.32-mm Hg lower SBP ( P =1.79×10 −7 ) and a 0.093-mm Hg/decade slower age-related rise in SBP ( P =3.05×10 −5 ). The effect of long-term exposure to lower SBP on coronary heart disease mediated by these polymorphisms was 2-fold greater than that observed in prospective cohort studies ( P =0.006) and 3-fold greater than that observed in short-term blood pressure treatment trials ( P =0.001). We conclude therefore that SBP seems to be causally associated with the rate of rise in SBP with age and has a cumulative effect on the risk of coronary heart disease.
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The MR study will likely reflect mean differences in maternal glucose levels across the whole of pregnancy, whereas the multivariable regression analyses in the pregnancy cohorts are based on one baseline measure of fasting glucose taken between 26 and 28 weeks of gestation and thus reflect lower glucose during the last 12-14 weeks of gestation.
“The MR study will likely reflect mean differences in maternal glucose levels across the whole of pregnancy, whereas the multivariable regression analyses in the pregnancy cohorts are based on one (baseline) measure of fasting glucose taken between 26 and 28 weeks of gestation and thus reflect lower glucose during the last 12–14 weeks of gestation (assuming, as in Ference et al.,53 that exposure”
From Triangulation in aetiological epidemiology (2017) · cites this paper as [53]
Effect estimates from all three approaches (MR, prospective cohorts, RCT) point in the same direction of lower SBP causing reduced odds of CHD, but magnitudes vary, being greatest for MR, intermediate for prospective cohorts, and least for RCTs.
“Effect estimates from all three approaches point in the same direction of lower SBP causing reduced odds of CHD (Figure 2a), but the magnitudes of this effect vary, being greatest for the MR studies, intermediate for the prospective cohorts and least for the RCTs.53”
From Triangulation in aetiological epidemiology (2017) · cites this paper as [53]
When we plot the effect of each approach against estimated duration of exposure, the results provide some support for a cumulative duration effect, with a biased (exaggerated) effect from the IV analyses in the RCT.
“When we plot the effect of each approach against estimated duration of exposure, as done by Ference et al.,53 the results provide some support for a cumulative duration effect, with a biased (exaggerated) effect from the IV analyses in the RCT (Figure 3b).”
From Triangulation in aetiological epidemiology (2017) · cites this paper as [53]
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- Authors
- Ference, B. A., Julius, S., Mahajan, N., Levy, P. D., Williams, K. A., & Flack, J. M.
- Affiliations
- Wayne State University (US)
- From the Divisions of Translational Research and Clinical Epidemiology (B.A.F., J.M.F.) and Cardiovascular Medicine (B.A.F., N.M., K.A.W.), Cardiovascular Research Institute (P.D.L.), and Department of Internal Medicine (J.M.F.), Wayne State University School of Medicine, Detroit, MI; and Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (S.J.).
- Venue
- Hypertension
- Published
- 2014-06
- Volume
- 63
- Issue
- 6
- Pages
- 1182-1188
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2155003407
- Cited by
- 77
- References
- 21
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 6 · 2019: 9 · 2018: 5 · 2017: 8 · 2016: 12 · 2015: 5
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- systolic blood pressure, genetic polymorphism, coronary artery disease, hypertension prevention, blood pressure reduction, causal relationship
- MeSH terms
- Adolescent, Adult, Age Factors, Antihypertensive Agents, Blood Pressure, Child, Coronary Disease, Gene Frequency, Humans, Hypertension, Middle Aged, Prospective Studies, Regression Analysis, Risk Factors, Time Factors, Meta-Analysis as Topic, Randomized Controlled Trials as Topic, Outcome Assessment, Health Care, Risk Assessment, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Young Adult
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