Effect of Hydrochlorothiazide and Hypokalemia on Left Ventricular Hypertrophy in Hypertensive Patients

November 16, 2009
Todd Kunkler

The results of a study that looked at the competing effects on left ventricular hypertrophy (LVH) of hypokalemia and treatment with hydrochlorothiazides (HCTZ) in hypertensive patients were presented Monday, November 15 at the American Heart Association Scientitifc Sessions 2009.

Effect of Hydrochlorothiazide and Hypokalemia on Left Ventricular Hypertrophy in Hypertensive Patients

The results of a study that looked at the competing effects on left ventricular hypertrophy (LVH) of hypokalemia and treatment with hydrochlorothiazides (HCTZ) in hypertensive patients were presented Monday, November 15 at the American Heart Association Scientitifc Sessions 2009. The study, titled "Competing Effects of Hypokalemia and Hydrochlorothiazide Treatment on Regression of Cornell Product Left Ventricular Hypertrophy in Hypertensive Patients: Implications for Development of Potassium-Sparing Diuretics," was presented during the afternoon poster sessions by Peter M. Okin, MD, and colleagues from Weill Cornell Medical College.

The study noted that although treatment with HCTZ is associated with blood pressure reduction and regression of LVH, HCTZ use is also associated with hypokalemia (hypoK), which "increases blood pressure and is associated with a greater likelihood and severity of electrocardiographic (ECG) LVH." To examine these possibly competing effects, the researchers looked at "baseline and yearly Cornell product (CP) ECG LVH levels" in relation to hypoK and HCTZ use in 7,816 patients in the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study.

Patients on HCTZ had lower potassium (serum K) levels at year 1 (4.05 ± 0.38 vs 4.24 ± 0.38), year 2 (4.04 ± 0.38 vs 4.25 ± 0.38), year 3 (4.04 ± 0.39 vs 4.27 ± 0.39) and year 4 (4.05 ± 0.41 vs 4.26 ± 0.38). In patients with hypoK who were not treated with HCTZ, change in CP LVH (expressed in mm/msec) from baseline to year one was -113±826, -137±656 at year 2, -135±860 at year 3, and -145±704 at year 4. In patients with normal serum K who were not treated with HCTZ, change in CP LVH from baseline to year 1 was -133±726, 194±735 at year 2, -171±752 at year 3, and -188±784 at year 4.

In patients with hypoK who received treatment with HCTZ, change in CP LVH from baseline to year 1-152±628, -224±653 at year 2, -237±692 at year 3, and -228±751 at year 4. In patients with normal serum K who were treated with HCTZ change in CP LVH from baseline to year 1 was -213±673, -276±762 at year 2, -283±749 at year 3, and -261±815 at year 4.

After adjusting for age, sex, race, and other factors, the researchers determined that hypoK was "associated with less mean reduction of CP LVH," but that "HCTZ use was associated with greater regression of CP LVH between baseline and years 1 to 4." Analysis of the data also revealed that hypoK was associated with a 15-19% lower likelihood of a reduction in CP LVH (median value greater than or equal to 236 mm/ms), yet HCTZ treatment was associated with an 18-33% greater likelihood of CP LVH regression between baseline and years 1 to 4.

The researchers conclude that HCTZ was associated with lower in-treatment serum K and independently associated with "a greater magnitude and likelihood of LVH regression during antihypertensive therapy." HypoK was associated with "a competing lower likelihood and magnitude of regression" of CP LVH. The data suggest that hypoK may "independently blunt regression of LVH during treatment," leading the researchers to conclude that "aggressive K repletion and/or the development of K-sparing thiazide diuretics could improve LVH regression and, as a consequence, possibly improve prognosis in hypertensive patients."