Evidence for reverse causality in the association between blood pressure and cardiovascular risk in patients with chronic kidney disease
Herrington W., Staplin N., Judge P., Mafham M., Emberson J., Haynes R., Wheeler DC., Walker R., Tomson C., Agodoa L., Wiecek A., Lewington S., Reith C., Landray M., Baigent None.
Among those with moderate-to-advanced chronic kidney disease, the relationship between blood pressure and cardiovascular disease appears ‘U’-shaped, but is loglinear in apparently healthy adults. The Study of Heart and Renal Protection randomized 9270 patients with chronic kidney disease to simvastatin/ezetimbe versus matching placebo, and measured blood pressure at each follow-up visit. Cox regression was used to assess the association between blood pressure and risk of cardiovascular disease among:(i) those with a self-reported history of cardiovascular disease; and (ii) those with no such history and, based on plasma troponin-I concentration, a low probability of subclinical cardiac disease. 8666 participants had a valid baseline blood pressure and troponin-I measurement and 2188 had at least one cardiovascular event during follow-up. After adjustment for relevant confounders, the association between systolic blood pressure and cardiovascular events was ‘U’-shaped, but among participants without evidence of prior cardiovascular disease, there was a positive loglinear association throughout the range of values studied. Among those with the lowest probability of subclinical cardiac disease, each 10mmHg higher systolic blood pressure corresponded to a 27% increased risk of cardiovascular disease (hazard ratio 1.27, 95% confidence interval 1.11-1.44). In contrast, the relationship between diastolic blood pressure and cardiovascular risk remained ‘U’-shaped irrespective of cardiovascular disease history or risk of subclinical disease. In conclusion, the lack of a clear association between systolic blood pressure and cardiovascular risk in this population appears attributable to confounding, suggesting that more intensive systolic blood pressure reduction may be beneficial in such patients.