High salt intake is associated with target organ damage independently of BP

Abstract

reduction of asleep BP by bedtime hypertension treatment significantly reduces the risk of cardiovascular events. Whether such benefits might also apply to other conditions remains uncertain. We evaluated the potential differential administration-time-dependent effects on the risk of chronic kidney disease (CKD) of the various classes of hypertension medications. We conducted a prospective, randomized, open-label, blinded endpoint trial on 2078 hypertensive patients without CKD, 1017 men/ 1061 women, 53.6 13.7 years of age. Patients were randomized to ingest all their prescribed hypertension medications upon awakening or the entire daily dose of 1 of them at bedtime. At baseline and annually (or more frequently if hypertension treatment was adjusted based on ambulatory BP) thereafter, BP and physical activity (wrist actigraphy) were simultaneously monitored for 48h. During a 5.9-year median follow-up, 368 patients developed CKD (estimated glomerular filtration rate <60 ml/min/ 1.73 m2, albuminuria, or both, at least twice within 3 months). Patients ingesting 1 hypertension medications at bedtime evidenced a significantly lower risk of CKD than those ingesting all medications upon awakening, independent of class. Greater benefits were observed for bedtime compared to awakening treatment with ACEIs (adjusted hazard ratio: 0.20 [95%CI: 0.10-0.38]; P<0.001) and ARBs (0.47 [0.32-0.69], P<0.001). There were no differences in the risk of CKD between of all six classes of tested medications in patients randomized to ingest them upon awakening. Treatment at bedtime with ACEIs, however, was associated with significantly lower hazard ratio of new-onset CKD than ingestion of other classes of medications also at bedtime. Bedtime hypertension treatment significantly reduces the risk of developing CKD compared to conventional morning dosing independent of the class of BP-lowering medication used for treatment. There is no advantage of any particular class of medication when ingested upon awakening. Renin-angiotensin blockade, however, is significantly superior to any other BP-lowering strategy for reducing the risk of CKD, apart from the documented decrease of cardiovascular risk, when the medications are dosed at bedtime.