Individual variability in response to renin angiotensin aldosterone system inhibition predicts cardiovascular outcome in patients with type 2 diabetes: A primary care cohort study

Diabetes Obes Metab. 2018 Jun;20(6):1377-1383. doi: 10.1111/dom.13226. Epub 2018 Feb 20.


Aims: To assess variability in systolic blood pressure (SBP) and albuminuria (urinary albumin creatinine ratio [UACR]) responses in patients with type 2 diabetes mellitus initiating renin angiotensin aldosterone system (RAAS) inhibition, and to assess the association of response variability with cardiovascular outcomes.

Material and methods: We performed an observational cohort study in patients with type 2 diabetes who started RAAS inhibition between 2007 and 2013 (n = 1600). Patients were identified from general practices in the Netherlands. Individual response in SBP and UACR was assessed during 15 months' follow-up. Patients were categorized as: good responders (∆SBP <0 mm Hg and ∆UACR <0%); intermediate responders (∆SBP <0 mm Hg and ∆UACR >0% or ∆SBP >0 mm Hg and ∆UACR <0%); or poor responders (∆SBP >0 mm Hg and ∆UACR >0%). Multivariable Cox regression was performed to test the association between initial RAAS inhibition response and subsequent cardiovascular outcomes.

Results: After starting RAAS inhibition, the mean SBP change was -13.2 mm Hg and the median UACR was -36.6%, with large between-individual variability, both in SBP [5th to 95th percentile: 48.5-20] and UACR [5th to 95th percentile: -87.6 to 171.4]. In all, 812 patients (51%) were good responders, 353 (22%) had a good SBP but poor UACR response, 268 (17%) had a good UACR but poor SBP response, and 167 patients (10%) were poor responders. Good responders had a lower risk of cardiovascular events than poor responders (hazard ratio 0.51, 95% confidence interval 0.30-0.86; P = .012).

Conclusions: SBP and UACR response after RAAS inhibition initiation varied between and within individual patients with type 2 diabetes treated in primary care. Poor responders had the highest risk of cardiovascular events, therefore, more efforts are needed to develop personalized treatment plans for these patients.

Keywords: RAAS inhibition; primary care; type 2 diabetes mellitus; variability in response.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / etiology
  • Albuminuria / prevention & control
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antihypertensive Agents / therapeutic use
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / epidemiology
  • Diabetic Angiopathies / physiopathology
  • Diabetic Angiopathies / prevention & control
  • Diabetic Cardiomyopathies / epidemiology
  • Diabetic Cardiomyopathies / prevention & control
  • Drug Resistance*
  • Drug Resistance, Multiple
  • Electronic Health Records
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Hypertension / urine
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Primary Health Care
  • Risk


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents