COLORADO SPRINGS — The intake ratio of sodium to potassium bears a much stronger association with subsequent development of cardiovascular disease than does consumption of either alone, according to new findings from the Trials of Hypertension Followup (TOPH) Study.
“We found that sodium and potassium may have a joint effect on the development of cardiovascular disease, in keeping with a proposed biologic symmetry. In our data the ratio was the most important predictor,” Nancy R. Cook, Sc.D., reported at a conference of the American Heart Association.
She presented a 10- to 15-year follow-up of 2,275 participants in TOPH-I and -II, a pair of National Institutes of Health- sponsored randomized clinical trials of sodium reduction and other interventions aimed at preventing hypertension in individuals who were prehypertensive at baseline. There were 193 cardiovascular events—acute myocardial infarction, stroke, revascularization procedures, or cardiovascular death—during follow-up.
A key feature of both studies was the periodic collection of 24-hour urine sodium and potassium excretions over several years.
“Most observational studies have had an imperfect measure of exposure. It's very difficult to capture sodium on a food-frequency questionnaire because it's so much affected by what you add at the table or what's in processed food products. It really varies by product and brand. Also, a single urinary excretion may not reflect usual intake over a longer period of time,” noted Dr. Cook of Brigham and Women's Hospital, Boston, and the Harvard School of Public Health.
In the TOPH follow-up analysis, there was a significant, linear relationship with cardiovascular risk from lowest to highest quartile of the sodium to potassium excretion ratio. After full statistical adjustment for numerous variables, including demographics, alcohol intake, body weight, physical activity, smoking status, and changes in those variables over the course of the study, individuals in the highest quartile of sodium to potassium ratio had a highly significant 50% increased risk of a cardiovascular event during follow-up, compared with those in the lowest quartile.
For each unit increase in sodium to potassium ratio, future cardiovascular risk rose by 24%, she added.
The mean ratio was 2.9 in both men and women in the study population as a whole. But it differed modestly by age and more profoundly by race. Black participants had lower potassium excretion levels than whites, leading to a much higher sodium to potassium ratio of 3.4.
Considered separately, neither sodium nor potassium excretion alone was significantly related to cardiovascular risk across quartiles.
Audience member Dr. Francesco P. Cappuccio observed that most of the Western world is now moving toward a generalized reduction in sodium intake at a population level in order to prevent cardiovascular disease. But the new TOPH analysis suggests an alternative approach may be better.
“Should we be looking into the use of salt substitutes in which sodium chloride is replaced by potassium in order to convey more cardiovascular protection? We know that increasing potassium intake through dietary means alone—eating more fruits and vegetables—is as hard as decreasing the salt in processed food,” said Dr. Cappuccio, professor of clinical sciences at Warwick Medical School, Coventry, England.
Dr. Cook replied that such an approach “would certainly be compatible” with the TOPH findings.
She noted that a small trial in Taiwan has demonstrated decreased cardiovascular mortality with the use of a potassium-based salt substitute, compared with ordinary table salt.