Changes in subclinical organ damage vs. in Framingham risk score for assessing cardiovascular risk reduction during continued antihypertensive treatment: a LIFE substudy

Abstract

To investigate whether in-treatment measurements of subclinical organ damage (SOD) assessed by elevated urine albumin/creatinine ratio (UACR) or electrocardiographic left ventricular hypertrophy improved the prediction of the composite cardiovascular endpoint of cardiovascular death, nonfatal myocardial infarction and stroke beyond in-treatment Framingham risk score (FRS). Excluding patients with a composite cardiovascular endpoint within the first year of treatment, 598 endpoints occurred in 6460 patients from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study with baseline and 1 year values for UACR, left ventricular hypertrophy by electrocardiography and FRS available. Using Cox-regression analyses, FRS(1year) [hazard ratio=1.006 (0.98-1.04)] did not predict the endpoint independently of history of cardiovascular disease [hazard ratio=1.76 (1.49-2.08)], FRS(baseline) [hazard ratio=1.07 (1.04-1.11)], UACR(baseline) [hazard ratio=1.15 (1.07-1.23), all three P<0.001], Sokolow-Lyon(baseline) [hazard ratio=1.01 (1.006-1.02), P<0.01] and treatment allocation, whereas Cornell product(1year) [hazard ratio=1.01 (1.006-1.02), P<0.001] and to some degree UACR(1year) [hazard ratio=1.05 (0.99-1.10), P=0.09] predicted the endpoint independently of history of cardiovascular disease [hazard ratio=1.71 (1.44-2.02)], FRS(baseline) [hazard ratio=1.08 (1.06-1.10)], Sokolow-Lyon(baseline) [hazard ratio=1.01 (1.007-1.02), both P<0.001], UACR(baseline) [hazard ratio=1.11 (1.03-1.20), P<0.01] and treatment allocation decreasing -2 Log likelihood significantly (P<0.01).Presence of left ventricular hypertrophy by Cornell product(1year) or UACR(1year) at least 1 mmol/l [hazard ratio=1.40 (1.15-1.70), P=0.001] but not FRS(1year) above the median baseline value of 20 [hazard ratio=1.22 (0.94-1.57), not significant] was associated with higher risk of subsequent endpoint after adjustment for history of cardiovascular disease [hazard ratio=1.82 (1.54-2.15)], FRS(baseline) at least 20 [hazard ratio=1.67 (1.30-2.16)], left ventricular hypertrophy by Sokolow-Lyon(baseline) or UACR(baseline) at least 1 mmol/l [hazard ratio=1.61 (1.33-1.94), all P<0.001] and treatment allocation [hazard ratio=0.93 (0.79-1.09), not significant]. In contrast to FRS(1year) at least 20 decreased, SOD(1year) decreased -2Log likelihood significantly (P<0.01). Cornell product(1year) and UACR(1year) improved in contrast to FRS(1year) risk prediction based on FRS(baseline), Sokolow-Lyon(baseline) and UACR(baseline) significantly in LIFE patients during antihypertensive treatment.