Hypertension is a primary risk factor for cardiovascular and cerebrovascular diseases, and renal failure. It is well known that the quantity of dietary salt intake plays a role in the pathogenesis of primary hypertension. Increased sensitivity of blood pressure to excess sodium affects 50% of patients with primary hypertension.1,2 Dietary salt intake causes an increase in blood pressure, and is associated with renal and cardiovascular diseases, including left ventricular hypertrophy and microalbuminuria.3–5 Spontaneous variation in blood pressure is referred to as blood pressure variability (BPV), and is classified as short-term BPV and long-term BPV.6,7 Fluctuation during a 24-h period is referred to as short-term BPV and is based on 24-h ambulatory blood pressure monitoring (ABPM). Variation between successive ABPM measurements is known as average real variability (ARV), which is mathematically calculated.8,9 BPV was reported to be associated with hypertension-related target organ damage and cardiovascular mortality, independent of the blood pressure level. BPV, therefore, becomes more important day-by-day.10–13 The pathophysiology of BPV is not fully known; however, it was reported that short-term BPV is primarily indicative of the effects of central and reflex autonomic modulation, and is associated with humoral, rheological, emotional, and behavioral factors.9,14–18 The relationship between dietary salt intake and ambulatory BPV is not clearly known. Dietary salt intake is known to adversely affect the cardiovascular system, independent of the blood pressure level.3,5 Excretion of sodium in 24-h urine is a measurement with proven validity that is commonly used to measure daily salt intake.19,20 The aim of the present study was to determine if the quantity of daily salt intake is associated with ambulatory BPV.

The study included 136 patients (92 male and 44 female). Mean age of the patients was 50.78±11.1 years. Patient demographic characteristics, and laboratory and ABPM findings are shown in Table 1. BPV and mean 24-h blood pressure levels, and the correlations between other parameters are shown in Table 2.

Systolic blood pressure level was positively correlated with log(24-h urinary sodium) (r=0.294, p=0.024), BMI (r=0.183, p=0.033), creatinine (r=0.226, p=0.008), 24-h systolic ARV (r=0.317, p=0.001), and nighttime systolic ARV (r=0.375, p=0.001).

Diastolic blood pressure level was positively correlated with log(24-h urinary sodium) (r=0.293, p=0.025), BMI (r=0.192, p=0.030), creatinine (r=0.201, p=0.019), 24-h diastolic ARV (r=0.333, p=0.006), and nighttime diastolic ARV (r=0.384, p=0.001).

Mean 24-h systolic ARV, mean nighttime systolic ARV, and mean systolic blood pressure did not significantly differ according gender. Mean 24-h systolic ARV, nighttime systolic ARV, and mean systolic blood pressure did not significantly differ between the patients that did and did not use anti-hypertensive drug.

Mean 24-h diastolic ARV, mean nighttime diastolic ARV blood pressure, and diastolic blood pressure did not significantly differ by gender. Mean 24-h diastolic ARV, mean nighttime diastolic ARV blood pressure, and diastolic blood pressure did not significantly differ between patients that did and did not use anti-hypertensive medication.

In evaluation of all patients for types of antihypertensive drugs used, means of blood pressure levels and ARVs for patients received renin angiotensin system blocker, calcium channel blocker, and beta blocker were similar (p>0.05).

Log(24-h urinary sodium) did not significantly differ according to gender, or anti-hypertensive drug class, and was not associated with other laboratory findings.

The positive correlation between log(24-h urinary sodium) and 24-h systolic ARV, and nighttime systolic ARV, 24-h diastolic ARV, nighttime diastolic ARV persisted when the effect of systolic and diastolic blood pressure levels were adjusted for.

Log(24-h urinary sodium) was positively correlated with mean 24-h systolic ARV and nighttime systolic ARV (r=0.371 and p=0.001, r=0.329 and p=0.028, respectively) (Figs. 1 and 2). Similarly, log(24-h urinary sodium) was positively correlated with mean 24-h diastolic ARV and nighttime diastolic ARV (r=0.381 and p=0.001, r=0.320 and p=0.020, respectively) (Figs. 3 and 4). The positive correlation also persisted when systolic and diastolic blood pressures, gender and BMI were adjusted for.

Fig. 1.

The correlation with 24-h systolic ARV and log(24-h urinary sodium).

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Fig. 2.

The correlation with nighttime systolic ARV and log(24-h urinary sodium).

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Fig. 3.

The correlation with 24-h diastolic ARV and log(24-h urinary sodium).

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Fig. 4.

The correlation with nighttime diastolic ARV and log(24-h urinary sodium).

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Age, male gender, BMI, duration of hypertension, and anti-hypertensive drug class, systolic blood pressure, diastolic blood pressure, log(24-h urine sodium), 24-h urine microalbuminuria, 24-h urine protein excretion, glucose, GFR, albumin, serum sodium, creatinine, triglyceride, and LDL levels were included in a stepwise regression model. Log(24-h urine sodium) was observed to be an independent predictor of BPV based on multivariate regression analysis (Table 3).

In the present study there was a positive correlation between the 24-h urine sodium level and 24-h systolic and 24-h diastolic BPV derived from ABPM in patients diagnosed as primary hypertension. In addition, there was a positive correlation between 24-h urine sodium, and mean 24-h systolic and 24-h diastolic blood pressure levels based on ABPM. The effect of the quantity of dietary salt intake on blood pressure has been investigated in numerous epidemiological screening studies, clinical studies, and experimental animal trials1,22–24; however, to the best of our knowledge the present study is the first to investigate the relationship between the quantity of daily salt intake and ambulatory BPV in hypertensive patients.

Dietary salt intake is a rectifiable environmental factor associated with the pathogenesis of primary hypertension. Conclusive evidence shows that high-level dietary salt intake is closely associated with high blood pressure and the development of hypertension-related target organ damage20,24,25; however, many studies report that high dietary sodium intake negatively affects the cardiovascular and cerebrovascular systems, independent of elevated blood pressure.26 It has been suggested that high dietary salt intake adversely affects remodeling in central and peripheral arteries, and increases arterial stiffness, independent of increasing blood pressure.27,28 A study that included normotensive participants reported that sodium excretion in 24-h urine was positively correlated with CIMT, independent of blood pressure, which was suggested to be because a high-salt diet could result in a flow-related increase in shear stress and induce compensatory arterial wall thickening without increasing blood pressure.

Endothelium-dependent vascular function and arterial walls are negatively affected by salt load. These effects of high salt intake on target organs are linked to the fibrogenic activity of transforming growth factor (TGF)-beta1, as TGF-beta1 production has been shown to increase during high salt intake.29 High salt intake also stimulates vascular growth by increasing the response to angiotensin 2, vasopressin, and several growth factors. In general, BPV is considered to occur due to interaction between environmental, behavioral, neural (central or reflex), humoral (insulin, angiotensin II, bradykinin, endothelin-1, and nitric oxide), and myogenic factors14,15,30–32; however, the precise factors responsible for BPV remain unclear. Sympathovagal reflex has been shown to play a role in BPV in healthy individuals.32 Additionally, among the proposed vascular mechanisms of BPV is alteration in arterial distensibility.33 BPV was also associated with changes in arterial blood vessel walls, including a decrease in arterial compliance and an increase in arterial stiffness, in healthy young males and patients with cardiovascular disease.17,31

In the present study the observed correlation between 24-h urine sodium and ambulatory BPV might have been due to the effect of salt on the arterial system. Research has suggested that salt-sensitive hypertension was associated with the autonomic nervous system, and that the sympathetic nervous system was hyperactivated and the parasympathetic system was inhibited in such patients.34 These findings are consistent with experimental animal studies in which the blood pressure in rats decreased following sympathetic current blockade or severing of sympathetic nerves.35,36

The central nervous system is suggested to play an important role in producing and maintaining high blood pressure in individuals with salt-sensitive hypertension. Central and reflex autonomic modulation is known to play a role in the pathophysiology of BPV. Rat studies showed that BPV was associated with reduced cardiac baroreflex.37 A study on the association between BPV and daily salt intake in normotensive individuals reported that dietary salt intake negatively affected centrally mediated cardiovascular reflex, resulting in an increase in BPV. Several studies reported that BPV is regulated by sympathovagal balance and arterial distensibility.2–4 Based on these findings, several mechanisms might contribute to increased BPV in hypertensive patients with a high-salt diet. Increased BPV might be partially due to diminished baroreflex function associated with increased stiffness and reduced compliance in large elastic arteries.26,27 Dietary salt intake might directly regulate or activate sympathetic nerve activity, and might indirectly modulate BPV; however, the cross-sectional design of the present study limits the ability to conclude that there is a causal relationship between salt intake and BPV.

In conclusion, the major finding of the present study is that primary hypertensive patients with high dietary salt intake had high BPV. The relationship between high salt intake and an increase in BPV was independent of the blood pressure level. These findings suggest that under similar blood pressure levels high salt intake may be associated with increased BPV. Additional larger-scale prospective studies are needed to further clarify the relationship between salt intake, BPV, and cardiovascular disease. Patients with a high-salt diet could be at increased risk for cardiovascular disease due to the adverse effects of BPV on the cardiovascular system. High dietary salt intake in hypertensive patients can result in elevated blood pressure and might contribute to cardiovascular morbidity due to an increase in blood pressure.

None to declare.

The authors report no conflicts of interest.