Antihypertensive treatment and risk of cardiovascular mortality in patients with chronic kidney disease diagnosed based on the presence of proteinuria and renal function: A large longitudinal study in Japan

PLoS One. 2019 Dec 4;14(12):e0225812. doi: 10.1371/journal.pone.0225812. eCollection 2019.

Abstract

Several recent clinical trials and meta-analyses have shown that lowering blood pressure reduces the risk of cardiovascular disease. However, current evidence that describes general demographics in blood pressure and mortality with chronic kidney disease is sparse in Japan. Using a population-based longitudinal cohort that received annual health checkups in Japan in 2008, hypertensive status, self-reported use of antihypertensive drugs, and prognosis were examined through 2012. Chronic kidney disease was defined as positive proteinuria or estimated glomerular filtration rate <60 ml/min/1.73 m2. Subjects were 40 to 74 years old (n = 227,204) with median 3.6 years follow-up period, and patients with and without chronic kidney disease were analyzed separately (n = 183,586 and n = 43,618, respectively). Cardiovascular disease mortality, comprising coronary heart diseases and stroke as entered in the national death registry using ICD-10 coding, was examined. Among all subjects, 346 deaths (96 in chronic kidney disease and 250 in non-chronic kidney disease) due to cardiovascular disease occurred. Compared with cardiovascular disease mortality in chronic kidney disease patients with untreated normal blood pressure, the multivariable adjusted hazard ratio was 3.08 (95% confidence interval: 1.75-5.41) for those with untreated hypertension, 2.30 (1.31-4.03) for those who became normotensive after treatment, and 3.28 (1.91-5.64) for those who remained hypertensive despite treatment. In non-chronic kidney disease subjects, the ratios were 1.90 (1.33-5.41), 1.95 (1.35-2.80), and 1.77 (1.18-2.66), respectively. These results from a nationwide cohort could be one of representative demographics of controlling blood pressure and cardiovascular disease deaths when treating patients with chronic kidney disease in Japan in recent years. Even after development and spread of anti-hypertensive drugs, preventing development of hypertension is preferable, because any hypertension treatment status comparing untreated normal blood pressure was a risk of cardiovascular mortality at baseline year.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents / adverse effects*
  • Antihypertensive Agents / therapeutic use
  • Biomarkers
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Japan / epidemiology
  • Kidney Function Tests
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Proteinuria / diagnosis
  • Proteinuria / etiology
  • Public Health Surveillance
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / mortality*
  • Risk Assessment
  • Risk Factors

Substances

  • Antihypertensive Agents
  • Biomarkers

Grants and funding

KY was granted from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP17ek0310005, JP18/JP19ek0310010 and 18lk1010033. (https://www.amed.go.jp/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.