Lithium Countertransport and Blood Pressure In CARDIA and TOMHS

BACKGROUND:

CARDIA was a longitudinal study of the influence of lifestyle on coronary heart disease risk factors during the young adult and post-young-adult years, the time period during which risk for cardiovascular disease was thought to undergo crucial evolution. Four centers participated in this study. The Chicago CARDIA population consisted of 1,100 Black and white men and women age 18 to 30 at baseline, of diverse socioeconomic backgrounds.

TOMHS was a two phase double-blind randomized controlled clinical trial to determine whether pharmacologic therapy in conjunction with nutritional-hygienic intervention for persons with mild hypertension results in greater reduction of cardiovascular morbidity than nutritional-hygienic treatment alone. Four clinical centers were involved in Phase I. Participants were randomized into one of six treatment groups. Each group received nutritional-hygienic treatment plus one of the following: placebo, diuretic, alpha blocker, beta blocker, angiotensin-converting enzyme inhibitor, calcium channel blocker. Randomization was stratified to assure balance within each treatment group with regard to participants' drug treatment status prior to randomization. The primary endpoint was cardiovascular morbidity.

Abnormalities in cellular sodium metabolism have long been thought to play a role in the pathogenesis of hypertension. Techniques for measuring membrane electrolyte transport rates have been refined, providing an opportunity to characterize sodium metabolism in cells from hypertensives. The early clinical studies examined erythrocytes and leukocytes because of their easy accessibility and the possibility that they would reflect vascular tissue metabolism, and documented differences in sodium fluxes between hypertensives and normotensives. Subsequent studies have supported the early findings that abnormalities in membrane cation transport were associated with essential hypertension.

The findings up to 1988 indicated that one or more transport systems might be altered in essential hypertension but each system was not affected similarly, nor did all hypertensives show the same changes in each of the transport systems studied. The most consistent findings have been observed for sodium-stimulated lithium countertransport (LCT). Clinical and population-based studies have revealed that mean LCT is significantly elevated among hypertensives. In contrast, increased, decreased, and normal mean values have been reported for sodium cotransport, and increased or normal mean values for adenosine triphosphate (ATP)-dependent sodium-potassium pump activity.