To the Editor,
Although the effect of salt intake and sensitivity on blood pressure (BP) has been well established, the mechanisms and contributing external factors are yet to be elucidated. Increased drinking frequency, as determined by Yoshimura et al in their study titled “Drinking frequency modifies an association between salt intake and blood pressure: A cohort study,” was associated with increased salt sensitivity. In particular, they found that alcohol consumption (categorized into rare, occasional, and daily) modified the association between change in salt intake (Δsalt intake) and change in BP (ΔBP). 1 We applaud the authors’ efforts to elaborate on this potentially important effect of alcohol and would like to offer alternate mechanisms as well as put into context key limitations that may need to be addressed in future studies.
The authors speculate that alcohol‐induced vasodysfunction, as a result of nitric oxide inhibition, may lead to increased salt sensitivity. 1 Several other possible mechanisms exist, including blunted renin‐angiotensin‐aldosterone system (RAAS) response, 2 potassium and calcium imbalances, 3 presence of confounding factors (eg, diet, exercise), 4 increased visit‐to‐visit BP variability, 5 and insulin resistance due to hepatic steatosis. 6
Alcohol can impact the RAAS pathway by inappropriately suppressing renin's response to changing sodium levels. 2 Alternatively, Criqui et al found that calcium depletion, which can also result in increased water and sodium reabsorption, was more apparent in moderate and heavy drinkers. 7
Confounding factors such as diet, exercise, and stress 8 can impact alcohol's modifying effect on salt sensitivity. Those consuming alcohol daily tend to have other accompanying unhealthy habits such as exercise intolerance, higher caloric intake, and increased nutrient deficiencies. 8 Moderate‐to‐heavy drinkers may also have a greater number of comorbid conditions. All these can impact ΔBP as well as Δsalt intake. Although the authors found no significant association between alcohol frequency and ΔBP or Δsalt intake, it is equally important to assess the association between change in alcohol frequency and ΔBP or Δsalt intake to confidently surmise that alcohol frequency is an effect modifier rather than a confounder in this study.
Although Tanaka's equation has been validated in Japanese cohorts, it may not be accurate to use the equation in this ungeneralizable study population due to the low proportion of dyslipidemia and diabetes, which, along with other comorbidities (eg, kidney disease, GI abnormalities, vitamin deficiencies), can greatly impact salt excretion. 9 Furthermore, adjusting for age and BMI as covariates may skew measurements of salt intake because age and biometric measurements are used in its calculation as well.
Recent literature has pointed to an independent association between systolic, visit‐to‐visit BP variability, and cardiovascular disease and has led to the emergence of BP variability as a novel, prognostic indicator. 10 Jaubert et al also found that increased alcohol consumption was associated with higher daytime BP variability. 5 Future studies may need to account for BP variability as a confounding covariate as ΔBP may just be a measure of physiologic variability rather than a measure of the effect of Δsalt intake on ΔBP. Salt sensitivity can fluctuate as well, so ideally one should measure salt sensitivity on multiple days with a strict protocol on diet.
Lastly, alcohol may indirectly impact salt sensitivity through increased insulin resistance, which likely increases salt sensitivity through sympathetic nervous system stimulation. 3 Although heavy alcohol use and binge drinking is associated with insulin resistance, the association with low and moderate alcohol consumption is still inconclusive. 6
Overall, we believe the authors make a strong case for the effect modification of drinking frequency on salt sensitivity. Future studies should keep in mind alternate mechanisms, confounding variables, and the inevitable, individual genetic susceptibilities that may influence risk for and effects of salt sensitivity.
CONFLICT OF INTEREST
The authors declare that they have no competing interests.
ETHICAL APPROVAL
This study was exempt from Rutgers's Institutional Review Board approval.
REFERENCES
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