Diuretics do not reduce tissue sodium in patients with early hypertension

In patients with pre- or mild hypertension, sodium content in the skin and muscles did not decrease with dietary salt restriction or diuretic intervention over a period of 8 weeks, a study has shown.

Preventative measures are essential to reduce the incidence of hypertension and its complications. [Hypertension 2020;75:1334-1357] “Sodium stored in skin and muscle tissue is associated with essential hypertension … [As such, we evaluated] the effects of diuretic therapy on mobilizing tissue sodium content in patients with early stages of hypertension and no concurrent medical problems as part of a preventative goal initiative.”

Of the 98 participants enrolled, 54 completed the study (median age 49.6 years, 67 percent female). They were randomized 1:1:1:1 to undergo a low-sodium diet (<2 g), daily diuretic therapy with the thiazide chlorthalidone 25 mg or the MRA* spironolactone 50 mg, or placebo for 8 weeks. Participants had systolic blood pressure (SBP) of 120–139 mm Hg and diastolic BP of 70–89 mm Hg. [J Am Heart Assoc 2022;11:e022723]

After adjusting for age, race, sex, baseline muscle sodium, BMI, and SBP, compared with the placebo arm, muscle sodium was significantly increased in the diet (β, 0.14) and chlorthalidone arms (β, 0.13; p<0.01 for both) at week 8. The effect with chlorthalidone may have been due to the sodium retention in response to the thiazide, the researchers explained.

Diet also substantially increased skin sodium by week 8 after adjusting for confounders (β, 0.17; p<0.01).

The divergent effects observed between muscle and skin sodium imply that the two compartments may be regulated by different mechanisms, the researchers pointed out.

There were no changes in pulse wave velocity (PWV) across the diet, spironolactone, and chlorthalidone arms when compared against placebo (median differences 0.1, 0.0, and −0.2 m/s vs 0.1 m/s). “[Although] these findings might suggest a lack of any biological link, a longer treatment period with a more effective reduction in tissue sodium stores might lead to improvements in arterial stiffness,” they continued.

A preventive strategy for BP control?

“[Our] primary aim … was to provide a preventive strategy for BP control, [but our findings demonstrate that] diuretic therapy for 8 weeks did not reduce muscle or skin sodium or improve PWV in patients with elevated BP or stage 1 hypertension,” the researchers stressed.

Further investigation is therefore warranted to determine other factors that could mobilize tissue sodium, as well as the role of tissue sodium removal in cardiovascular outcomes.

It should be noted that participants did not have high tissue sodium concentrations at baseline. Also, participants had minimal comorbidities, mild hypertension, and no significant kidney disease, which may have impacted the findings. Other influencing factors are insufficient dosing and potency of diuretics, as well as nonadherence to diet or pills for which data were lacking.

“Efforts to mobilize tissue sodium should be targeted to patients who are more likely to be at risk (ie, those with impaired kidney function and other comorbidities),” they added. “In such populations, sodium stores may be high enough to exert a clinical effect and excreting sodium from tissue then could result in clinically detectable change.”