Case report: Twice-daily tolvaptan dosing regimen in a challenging case of hyponatremia due to SIAD.

Background: Syndrome of inappropriate antidiuresis (SIAD) is one of the most frequent causes of euvolemic hyponatremia (serum sodium levels < 135 mEq/L) and it represents more than 35% of hyponatremia cases in hospitalized patients. It is characterized by an inappropriate vasopressin (AVP)/antidiuretic hormone (ADH) secretion, which occurs independently from effective serum osmolality or circulating volume, leading to water retention via its action on type 2 vasopressin receptor in the distal renal tubules. Corpus callosum agenesis (CCA) is one of the most common congenital brain defects, which can be associated to alterations in serum sodium levels. This report presents a rare case of chronic hyponatremia associated with SIAD in a woman with CCA, whose correction of serum sodium levels only occurred following twice-daily tolvaptan administration. Case presentation: A 30-year-old female was admitted to our hospital for non-acute hyponatremia with dizziness, headache, distal tremors, and concentration deficits. She had profound hyponatremia (Na 121 mmol/L) with measured plasma hypo-osmolality (259 mOsm/Kg) and urinary osmolality greater than 100 mOsm/Kg (517 mOsm/Kg). She presented clinically as normovolemic. After the exclusion of other causes of normovolemic hyponatremia, such as hypothyroidism and adrenal insufficiency, a diagnosis of SIAD was established. We have ruled out paraneoplastic, inflammatory, and infectious causes, as well as ischemic events. Her medical history showed a CCA and frontal teratoma. We administered tolvaptan initially at a low dosage (15 mg once a day) with persistence of hyponatremia. Therefore, the dosage was first doubled (30 mg once a day) and then increased to 45 mg once a day with an initial improvement in serum sodium levels, although not long-lasting. We therefore tried dividing the 45 mg tolvaptan administration into two doses of 30 mg and 15 mg respectively, using an off-label treatment schedule, thus achieving long-lasting serum sodium levels in the low-normal range associated with a general clinical improvement. Conclusions: This report underlines the importance of the correct diagnosis, management and treatment of SIAD, as well as the need for further studies about the pharmacokinetics and pharmacodynamics of vasopressin receptor antagonists.

Left Ventricular Mass Reduction by a Low-Sodium Diet in Treated Hypertensive Patients.

OBJECTIVE: To evaluate the left ventricular mass (LVM) reduction induced by dietary sodium restriction. PATIENTS AND METHODS: A simple sodium-restricted diet was advised in 138 treated hypertensives. They had to avoid common salt loads, such as cheese and salt-preserved meat, and were switched from regular to salt-free bread. Blood pressure (BP), 24-h urinary sodium (UNaV) and LVM were recorded at baseline, after 2 months. and after 2years. RESULTS: In 76 patients UNaV decreased in the recommended range after 2 months and remained low at 2 years. In 62 patients UNaV levels decreased after 2 months and then increased back to baseline at 2 years. Initially the two groups did not differ in terms of BP (134.3 ± 16.10 / 80.84 ± 12.23 vs.134.2 ± 16.67 / 81.55 ± 11.18 mmHg, mean ± SD), body weight (72.64 ± 15.17 vs.73.79 ± 12.69 kg), UNaV (161.0 ± 42.22 vs.158.2 ± 48.66 mEq/24 h), and LVM index (LVMI; 97.09 ± 20.42 vs.97.31 ± 18.91 g/m2). After 2years. they did not differ in terms of BP (125.3 ± 10.69 / 74.97 ± 7.67 vs.124.5 ± 9.95 / 75.21 ± 7.64 mmHg) and body weight (71.14 ± 14.29 vs.71.50 ± 11.87 kg). Significant differences were seen for UNaV (97.3 ± 23.01 vs.152.6 ± 49.96 mEq/24 h) and LVMI (86.38 ± 18.17 vs.103.1 ± 21.06 g/m2). Multiple regression analysis: UNaV directly and independently predicted LVMI variations, either as absolute values (R2 = 0.369; ß = 0.611; p < 0.001), or changes from baseline to +2years. (R2 = 0.454; ß = 0.677; p < 0.001). Systolic BP was a weaker predictor of LVMI (R2 = 0.369; ß = 0.168; p = 0.027; R2 = 0.454; ß = 0.012; p = 0.890), whereas diastolic BP was not correlated with LVMI. The prevalence of left ventricular hypertrophy decreased (29/76 to 15/76) in the first group while it increased in the less compliant patients (25/62 to 36/62; Chi2p = 0.002). CONCLUSION: LVM seems linked to sodium consumption in patients already under proper BP control by medications.

Sodium Intake and Target Organ Damage in Hypertension-An Update about the Role of a Real Villain.

Salt intake is too high for safety nowadays. The main active ion in salt is sodium. The vast majority of scientific evidence points out the importance of sodium restriction for decreasing cardiovascular risk. International Guidelines recommend a large reduction in sodium consumption to help reduce blood pressure, organ damage, and cardiovascular risk. Regulatory authorities across the globe suggest a general restriction of sodium intake to prevent cardiovascular diseases. In spite of this seemingly unanimous consensus, some researchers claim to have evidence of the unhealthy effects of a reduction of sodium intake, and have data to support their claims. Evidence is against dissenting scientists, because prospective, observational, and basic research studies indicate that sodium is the real villain: actual sodium consumption around the globe is far higher than the safe range. Sodium intake is directly related to increased blood pressure, and independently to the enlargement of cardiac mass, with a possible independent role in inducing left ventricular hypertrophy. This may represent the basis of myocardial ischemia, congestive heart failure, and cardiac mortality. Although debated, a high sodium intake may induce initial renal damage and progression in both hypertensive and normotensive subjects. Conversely, there is general agreement about the adverse role of sodium in cerebrovascular disease. These factors point to the possible main role of sodium intake in target organ damage and cardiovascular events including mortality. This review will endeavor to outline the existing evidence.

Characteristics of current heart failure patients admitted to internal medicine vs. cardiology hospital units: the VASCO study.

The majority of patients hospitalized for heart failure (HF) are admitted to internal medicine (IM) rather than to cardiology (CA) units, but to date few studies have analyzed the characteristics of these two populations. In this snapshot survey, we compared consecutive patients admitted for HF in six IM units vs. one non-intensive CA unit. During the 6-month survey period, 467 patients were enrolled (127 in CA, 27.2% vs. 340 in IM, 72.8%). IM patients were almost 10 years older (CA 75 ± 10, IM 82 ± 8 years; p < 0.001), more frequently female (CA 39%, IM 55%; p = 0.002) and living at home alone (CA 12%, IM 21%; p = 0.017). The leading cause of hospitalization in both groups was acute worsening of HF (CA 42%, IM 53%; p = 0.031), followed by atrial fibrillation (CA 29%, IM 12%; p < 0.001) and infections (CA 24%, IM 27%; p = 0.563). Ischemic (CA 43%, IM 30%; p = 0.008) and dilated cardiomyopathy patients (CA 21%, IM 12%; p < 0.001) were primarily admitted to CA unit, whereas those with hypertensive heart disease to IM (CA 3%, IM 39%; p < 0.001). Left ventricular ejection fraction (LVEF) was available in 96% of CA patients, but only in 60% of IM patients (p = 0.001). Among patients with LVEF measured, those with LVEF < 40% were predominantly admitted to CA (CA 60%, IM 14%; p < 0.001), whereas those with LVEF ≥ 50% were admitted to IM (CA 21%, IM 33%; p = 0.019); 26% of IM patients were discharged without a known LVEF. Medical treatments also significantly differed, according to patients' clinical and instrumental characteristics in each unit. This study demonstrates important differences between HF patients hospitalized in CA vs. IM, and the need for a greater interaction between these two medical specialties for a better care of HF patients.

Low-Salt Intake Suggestions in Hypertensive Patients Do not Jeopardize Urinary Iodine Excretion.

A low-sodium diet is an essential part of the treatment of hypertension. However, some concerns have been raised with regard to the possible reduction of iodine intake during salt restriction. We obtained 24-h urine collections for the evaluation of iodine (UIE) and sodium excretion (UNaV) from 136 hypertensive patients, before and after 9 ± 1 weeks of a simple low-sodium diet. Body mass index (BMI), blood pressure (BP), and drug consumption (DDD) were recorded. Data are average ± SEM. Age was 63.6 ± 1.09 year. BMI was 25.86 ± 0.40 kg/m² before the diet and 25.38 ± 0.37 kg/m² after the diet (p < 0.05). UNaV decreased from 150.3 ± 4.01 mEq/24-h to 122.8 ± 3.92 mEq/24-h (p < 0.001); UIE decreased from 186.1 ± 7.95 µg/24-h to 175.0 ± 7.74 µg/24-h (p = NS); both systolic and diastolic BP values decreased (by 6.15 ± 1.32 mmHg and by 3.75 ± 0.84 mmHg, respectively, p < 0.001); DDD decreased (ΔDDD 0.29 ± 0.06, p < 0.05). UNaV and UIE were related both before (r = 0.246, p = 0.0040) and after the diet (r = 0.238, p = 0.0050). UNaV and UIE were significantly associated both before and after the diet (p < 0.0001 for both). After salt restriction UIE showed a non-significant decrease remaining in an adequate range. Our dietary suggestions were aimed at avoiding preserved foods, whereas the cautious use of table salt was permitted, an approach which seems safe in terms of iodine intake.

Simple dietary advice reduces 24-hour urinary sodium excretion, blood pressure, and drug consumption in hypertensive patients.

Sodium intake should be restricted to 100 mEq, that is, about 2.3 grams per day. Strict diets, however, are often cumbersome and seldom matched by rigorous compliance. We studied 291 patients on antihypertensive treatment, 240 of whom were instructed to avoid salty foods, such as cheese and cured meats, and to switch from regular bread to salt-free bread. The remaining 51 matched patients constituted a control group and received only generic dietary advice. Na[U]/24h, K[U]/24h, and office BP (automated repeated measurements) were recorded before dieting started and after 9 ± 1 weeks of dieting. Our intervention group showed a significant decrease in body weight (71.75 ± 14.0 to 70.54 ± 13.33 kg, P < .0001), sodium excretion (153.1 ± 44.61 to 133.5 ± 37.1 mEq/24h, P < .05), systolic and diastolic BP (134.16 ± 16.0 to 126.5 ± 10.53 mm Hg, P = .014 and 80.59 ± 11.47 to 75.9 ± 8.72 mm Hg, P = .026, respectively), and drug consumption (1.71 ± 0.91 to 1.49 ± 0.84 DDD, P < .05). The rate of responders to antihypertensive therapy increased (51.4% to 79.5%). In the control group neither significant nor substantial changes were seen. Our data suggest that even a minimal reduction in the apparent sodium intake (∼0.5 grams per day) can improve both BP values and responder rates in treated hypertensive patients, while reducing the consumption of antihypertensive drugs.

Prevalence of erectile dysfunction in a cohort of Italian hypertensive subjects.

The aim of this study was to evaluate the prevalence of erectile dysfunction (ED) in a cohort of Italian hypertensive men and the association with clinical and biochemical data. The study involved 270 consecutive hypertensive subjects aged 40-70 years evaluated in Italian Hypertension Centers of six hospitals from Liguria and Piedmont. ED was assessed through the self-administered questionnaire of the International Index of Erectile Function. Clinical history with ongoing drug treatment, various clinical parameters, biochemical data and evidence about the presence of subclinical target organ damage was collected. Twenty-seven subjects refused to answer the questionnaire (10%). Among the 243 remained subjects, 123 presented ED (50.6%). ED was highly related to age, systolic blood pressure, pulse pressure, smoking status, statin therapy and kidney function. The addition of a thiazide diuretic to an inhibitor of the renin-angiotensin system significantly increased the prevalence of ED. The prevalence of ED increased in relation with the number of hypotensive drug classes taken by the patients. ED was highly prevalent in this cohort of Italian hypertensive subjects and was associated with other cardiovascular risk factors, such as age, smoking status and kidney function. The role of ED as an early marker of cardiovascular disease is discussed.