Physicians' Academy for Cardiovascular Education

Higher blood pressure associated with higher risk of diabetes in population free of CVD

Emdin CA et al., J Am Coll Cardiol. 2015

Usual Blood Pressure and Risk of New-Onset Diabetes
Evidence From 4.1 Million Adults and a Meta-Analysis of Prospective Studies


Emdin CA, Anderson, SG, Woodward M et al.
J Am Coll Cardiol. 2015;66(14):1552-1562. doi:10.1016/j.jacc.2015.07.059

 

Background

The prevalence of type 2 diabetes (T2DM) is estimated to continue to increase to 55 million people worldwide by 2030 [1]. Because individuals with T2DM are at increased risk of major CV morbidity and mortality [2,3], prevention of diabetes is crucial in attempts to reduce the burden of CV disease.
Elevated blood pressure (BP) is associated with chronic inflammation [4] and endothelial dysfunction [5], both of which seem to modify diabetes risk [6,7]. Cohort studies that have reported on the association between BP and diabetes, have shown varying results. Moreover, the cohort studies have had limited power to investigate whether observed associations depended on important patient features. This study therefore analysed data of 4.1 million individuals with at least 1 year of follow-up (30-90 years old), free from diabetes and CV disease, in a contemporary UK primary care population (Clinical Practice Datalink (CPRD)), and a meta-analysis was performed of existing prospective studies to reliably determine the association between BP and diabetes.
 

Main results

  • In a Cox proportional hazard model, unadjusted HR for the risk of diabetes was 2.60, 95%CI: 2.58-2.62 per 20 mmHg higher SBP. Adjusting for age, sex and BMI attenuated diabetes risk (HR: 1.58, 95%CI: 1.57-1.60 per 200 mmHg higher SBP), while additional adjustment for smoking, antihypertensive therapy use, and lipid-lowering therapy had little effect.
  • Overall, a 10 mmHg higher DBP was associated with higher risk of new onset diagnosis (HR: 1.52, 95%CI: 1.51-1.54), across the whole range of BP.  
  • Baseline BMI affected the association between SBP and newly diagnosed diabetes (P(interaction)=0.0001). Individuals with BMI<25 kg/m2 a 20 mmHg higher SBP was associated with a greater proportional increase in the risk of diabetes (HR: 1.89, 95%CI: 1.84-1.89) than in those with BMI>35 kg/m2 (HR: 1.19, 95%CI: 1.16-1.22). Higher baseline absolute risk in the higher BMI-category did, however, lead to larger absolute diabetes risk increases per 20 mm Hg higher SBP.
  • Although relative diabetes risk per 20 mmHg higher usual SBP declined with increasing age, the absolute risk differences were similar across different age groups, due to increasing absolute risk of new onset diabetes.
  • In a pooled random effects meta-analysis of 30 prospective observational studies, each 20 mmHg higher usual SBP from prior cohort studies was associated with a higher risk of new diabetes (RR: 1.77, 95%CI: 1.53-2.05).

Conclusion

These analyses show, in a cohort of people without known previous vascular disease, that both SBP and DPB correlated to risk of new onset diabetes, across a broad spectrum of BP (no evidence of a nadir down to 11/70 mmHg). The strength of the association decreased with higher age and higher BMI, but risk of diabetes in older people and individuals with higher BMI is still substantial due to higher absolute risks in these populations. Further research should clarify whether the observed association is causal.
 

References

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2. Kannel WB, McGee DL. Diabetes and cardiovascular risk factors: the Framingham study. Circulation
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3. Taylor KS, Heneghan CJ, Farmer AJ, et al. Allcause and cardiovascular mortality in middle-aged people with type 2 diabetes compared with people without diabetes in a large U.K. primary care database. Diabetes Care 2013;36:2366–71.
4. Chamarthi B, Williams GH, Ricchiuti V, et al. Inflammation and hypertension: the interplay of interleukin-6, dietary sodium, and the renin-angiotensin system in humans. Am J Hypertens 2011;24:1143–8.
5. Taddei S, Virdis A, Ghiadoni L et al. Antihypertensive drugs and reversing of endothelial dysfunction in hypertension. Curr Hypertens Rep 2000;2:64–70.
6. Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet 2012;379:1214–24.
7. Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA 2004;291:1978–86.