Lithium Countertransport and Blood Pressure In CARDIA and TOMHS
Information source: National Heart, Lung, and Blood Institute (NHLBI)
Information obtained from ClinicalTrials.gov on December 31, 2007
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cardiovascular Diseases; Heart Diseases; Hypertension
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)
To conduct ancillary studies of sodium-stimulated lithium counter-transport in the Chicago
components of the Coronary Heart Disease Risk Development in Young Adults (CARDIA) cohort and
in the Treatment of Mild Hypertension Study (TOMHS) cohort.
Study design: Natural History
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
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.
The relationship between LCT and blood pressure has been examined in several studies. The
largest of these was an epidemiological survey involving 3,800 men and women age 5 to over 75
in Gubbio, Italy. LCT was significantly and positively associated with both systolic and
diastolic blood pressure in this population after controlling for age, sex, and weight, but,
after controlling also for other factors known to be related to blood pressure such as serum
uric acid and glucose, the relationship was inconsistently significant in this
cross-sectional study. In other cross-sectional research, LCT was found to account for three
percent of the variation in blood pressure in a study of healthy blood donors after
adjustment for weight and age. Other cross-sectional population-based studies involving
smaller numbers have shown a significant relationship between LCT and diastolic blood
pressure in adolescents and in white adults, but not among Black adults; also between LCT and
systolic blood pressure, but not diastolic blood pressure, in Black children and white
Much of the data available in 1988 had been derived from small numbers in cross-sectional
studies, chiefly clinical, only a few population-based. Large samples were needed to provide
adequate power to detect relationships among LCT and demographic, dietary, and other factors.
Prospective data were needed to assess whether LCT was an independent risk factor for future
development of high blood pressure in people normotensive at baseline, whether LCT could be
modified, and whether this change was associated with changes in blood pressure.
In the cross-sectional CARDIA investigation, studies were conducted on the relationships
among lithium countertransport, blood pressure, and factors related to blood pressure such as
age, sex, race, weight, body mass index, pulse, dietary factors, alcohol intake, serum
glucose, triglycerides, cholesterol, high density lipoprotein cholesterol, uric acid, and
ionized and total calcium. Prospective data were also collected from TOMHS to examine
whether lithium countertransport was modified in mild hypertension by diet or by a
combination of diet and antihypertensive drugs. Lithium countertransport was assayed in
erythrocytes at the second examination in CARDIA and at baseline, 12 months, and 24 months in
Minimum age: N/A.
Maximum age: N/A.
No eligibility criteria
Locations and Contacts
Starting date: March 1988
Ending date: February 1990
Last updated: June 23, 2005