In-Treatment Statin Use in Hypertensive Patients Linked to Risk of New Diabetes Mellitus

SAN FRANCISCO, CAPatients with hypertension and ECG left ventricular hypertrophy (LVH) being aggressively treated for blood pressure reduction had an increased risk of new diabetes mellitus with in-treatment—but not baseline—statin use, according to results of the Losartan Intervention For Endpoint Reduction (LIFE) study presented at ACC.13, the American College of Cardiology's 62nd Annual Scientific Session.

“These findings support previous results from randomized controlled trials and in postmenopausal women and suggest that hypertensive patients on statin therapy have periodic screening for diabetes,” Peter M. Okin, MD, of the Division of Cardiology of the Department of Medicine at Weill Cornell Medical College, New York, NY, and colleagues reported.

“Statins are important and useful,” he stated. However, diabetes has other consequences and these results suggest “we follow patients much more carefully.”

The investigators examined “the relationship of new diabetes mellitus occurring at 2 years or later during follow-up to the use of statin at baseline and during treatment in hypertensive patients with ECG LVH” to determine whether their association with new diabetes mellitus is independent of the prognostic value of a number of factors.

The LIFE study randomized 9,193 patients to losartan 50mg/day or atenolol 50mg/day and matching placebo of the other agent; target BP was ≤140/90mmHg. “Study therapy could be up-titrated by the addition of hydrochlorothiazide (HCTZ) 12.5mg followed by increase in blinded losartan or atenolol to 100mg daily, with additional open-label therapies as indicated,” they stated.

A total of 1,195 patients had diabetes mellitus at baseline. The study excluded patients with no baseline HDL measurement (n=513), those who developed new diabetes mellitus before 2 years (n=209), and those with <2 years follow-up (n=275), leaving 7,001 patients available for analysis.

Due to the small number of patients on statins at baseline (n=504, 7.2%), analysis was restricted to new onset diabetes ≥2 years after study enrollment. Study results showed that during 4.9+0.7 years follow up, new onset diabetes mellitus was diagnosed in 311 patients (4.4%).

“In univariate Cox analyses, in-treatment statin use treated as a time-varying covariate was associated with a 74% higher risk of new diabetes mellitus (HR 1.74, 95% CI 1.37-2.20),” they found. “In contrast, baseline statin use was not a significant predictor of new diabetes mellitus (HR 1.33, 95% CI 0.90-1.96).”

In multivariate Cox analyses (adjusted for randomized treatment, baseline age, sex, race, prior antihypertensive therapy, history of ischemic heart disease, myocardial infarction, heart failure or peripheral vascular disease, baseline serum glucose, creatinine and uric acid, logistic propensity score for statin use treated as standard covariates, and in-treatment Cornell product LVH, diastolic and systolic pressure, body mass index, HCTZ use, HDL and non-HDL cholesterol treated as time-varying covariates), in-treatment statin use was associated with an 106% increased risk of new diabetes mellitus (HR 2.06, 95% CI 1.59-2.68).

“The strong predictive value of in-treatment statin use persists and is not attenuated in multivariate models that adjust for other known and potential risk factors for diabetes, the propensity score for statin use, and for the previously demonstrated impact of losartan vs atenolol treatment, previous antihypertensive therapy, in-treatment HDL cholesterol levels and for the possible impact of concurrent treatment with HCTZ on the risk of developing diabetes,” Dr. Okin and colleagues concluded.