Relation of Alanine Aminotransferase Levels to Cardiovascular Events and Statin Efficacy.
The relation between hepatic serum markers within the normal range and cardiovascular risk is uncertain. We sought to address this issue within a prospective randomized trial of statin therapy. Men and women (n = 17,515) free of cardiovascular disease participating in a randomized placebo controlled trial of rosuvastatin 20 mg/day had baseline levels of alanine aminotransferase (ALT) below <40 IU/l and were followed prospectively for the first-ever cardiovascular events. Cox proportional hazards models were used to calculate the relative risks of these events according to increasing tertiles and each SD increase in baseline ALT levels. ALT levels at study entry, all within the normal range, were inversely associated with age, smoking status, and inflammation and were positively associated with male gender, alcohol use, and triglycerides. Incident cardiovascular event rates were highest in those in the lowest tertile of baseline ALT; specifically, incidence rates were 1.43, 0.98, and 0.85 per 100 person-years of exposure for those in the lowest, middle, and highest tertile of baseline ALT within the normal range, respectively (p <0.001). These inverse effects remained statistically significant after multivariate adjustment for a wide range of vascular risk factors risk markers such that each higher SD unit of ALT was associated with an 18% lower event rate (relative risk 0.82, 95% confidence interval 0.72 to 0.93, p = 0.002). The efficacy of statin therapy was not modified by baseline ALT level. In conclusion, increasing ALT levels within the normal range are inversely associated with future cardiovascular risk but had limited clinical utility and also did not modify the efficacy of statin therapy.
Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Paulo H N
PH
Harada
Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Nancy R
NR
Cook
Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
David E
DE
Cohen
Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Nina P
NP
Paynter
Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Lynda
L
Rose
Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: pridker@partners.org.
Paul M
PM
Ridker
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000453:epidemiology* / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*
D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; D000410:Alanine Transaminase