A State-of-Art Review of the Vicious Circle of Sleep Disorders, Diabetes and Neurodegeneration Involving Metabolism and Microbiota Alterations.

In the context of neurodegenerative disorders, cognitive decline is frequently reported in older population. Recently, numerous metabolic pathways have been implicated in neurodegeneration, including signaling disruption of insulin and other glucose-regulating hormones. In fact, Alzheimer's disease has now been considered as "type-3 diabetes". In this review, we tried to clarify the role of sleep impairment as the third major player in the complex relationship between metabolic and neurodegenerative diseases. Altered sleep may trigger or perpetuate these vicious mechanisms, leading to the development of both dementia and type 2 diabetes mellitus. Finally, we analyzed these reciprocal interactions considering the emerging role of the gut microbiota in modulating the same processes. Conditions of dysbiosis have been linked to circadian rhythm disruption, metabolic alterations, and release of neurotoxic products, all contributing to neurodegeneration. In a future prospective, gut microbiota could provide a major contribution in explaining the tangled relationship between sleep disorders, dementia and diabetes.

Lipoprotein(a): Just an Innocent Bystander in Arterial Hypertension?

Elevated plasma lipoprotein(a) [Lp(a)] is a relatively common and highly heritable trait conferring individuals time-dependent risk of developing atherosclerotic cardiovascular disease (CVD). Following its first description, Lp(a) triggered enormous scientific interest in the late 1980s, subsequently dampened in the mid-1990s by controversial findings of some prospective studies. It was only in the last decade that a large body of evidence has provided strong arguments for a causal and independent association between elevated Lp(a) levels and CVD, causing renewed interest in this lipoprotein as an emerging risk factor with a likely contribution to cardiovascular residual risk. Accordingly, the 2022 consensus statement of the European Atherosclerosis Society has suggested inclusion of Lp(a) measurement in global risk estimation. The development of highly effective Lp(a)-lowering drugs (e.g., antisense oligonucleotides and small interfering RNA, both blocking LPA gene expression) which are still under assessment in phase 3 trials, will provide a unique opportunity to reduce "residual cardiovascular risk" in high-risk populations, including patients with arterial hypertension. The current evidence in support of a specific role of Lp(a) in hypertension is somehow controversial and this narrative review aims to overview the general mechanisms relating Lp(a) to blood pressure regulation and hypertension-related cardiovascular and renal damage.

Omega-3 Fatty Acids in Arterial Hypertension: Is There Any Good News?

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including alpha-linolenic acid (ALA) and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are "essential" fatty acids mainly obtained from diet sources comprising plant oils, marine blue fish, and commercially available fish oil supplements. Many epidemiological and retrospective studies suggested that ω-3 PUFA consumption decreases the risk of cardiovascular disease, but results of early intervention trials have not consistently confirmed this effect. In recent years, some large-scale randomized controlled trials have shed new light on the potential role of ω-3 PUFAs, particularly high-dose EPA-only formulations, in cardiovascular prevention, making them an attractive tool for the treatment of "residual" cardiovascular risk. ω-3 PUFAs' beneficial effects on cardiovascular outcomes go far beyond the reduction in triglyceride levels and are thought to be mediated by their broadly documented "pleiotropic" actions, most of which are directed to vascular protection. A considerable number of clinical studies and meta-analyses suggest the beneficial effects of ω-3 PUFAs in the regulation of blood pressure in hypertensive and normotensive subjects. These effects occur mostly through regulation of the vascular tone that could be mediated by both endothelium-dependent and independent mechanisms. In this narrative review, we summarize the results of both experimental and clinical studies that evaluated the effect of ω-3 PUFAs on blood pressure, highlighting the mechanisms of their action on the vascular system and their possible impact on hypertension, hypertension-related vascular damage, and, ultimately, cardiovascular outcomes.

Arterial stiffening in hypertension: is it just high blood pressure?

No abstract present.

Prognostic scores and early management of septic patients in the emergency department of a secondary hospital: results of a retrospective study.

BACKGROUND: Sequential Organ Failure Assessment (SOFA) and other illness prognostic scores predict adverse outcomes in critical patients. Their validation as a decision-making tool in the emergency department (ED) of secondary hospitals is not well established. The aim of this study was to compare SOFA, NEWS2, APACHE II, and SAPS II scores as predictors of adverse outcomes and decision-making tool in ED. METHODS: Data of 121 patients (age 73 ± 10 years, 58% males, Charlson Comorbidity Index 5.7 ± 2.1) with a confirmed sepsis were included in a retrospective study between January 2017 and February 2020. Scores were computed within the first 24 h after admission. Primary outcome was the occurrence of either in-hospital death or mechanical ventilation within 7 days. Secondary outcome was 30-day all-cause mortality. RESULTS: Patients older than 64 years (elderly) represent 82% of sample. Primary and secondary outcomes occurred in 40 and 44%, respectively. Median 30-day survival time of dead patients was 4 days (interquartile range 1-11). The best predictive score based on the area under the receiver operating curve (AUROC) was SAPS II (0.823, 95% confidence interval, CI, 0.744-0.902), followed by APACHE II (0.762, 95% CI 0.673-0.850), NEWS2 (0.708, 95% CI 0.616-0.800), and SOFA (0.650, 95% CI 0.548-0.751). SAPS II cut-off of 49 showed the lowest false-positive rate (12, 95% CI 5-20) and the highest positive predictive value (80, 95% CI 68-92), whereas NEWS2 cut-off of 7 showed the lowest false-negative rate (10, 95% CI 2-19) and the highest negative predictive value (86, 95% CI 74-97). By combining NEWS2 and SAPS II cut-offs, we accurately classified 64% of patients. In survival analysis, SAPS II cut-off showed the highest difference in 30-day mortality (Hazards Ratio, HR, 5.24, 95% CI 2.99-9.21, P < 0.001). Best independent negative predictors of 30-day mortality were body temperature, mean arterial pressure, arterial oxygen saturation, and hematocrit levels. Positive predictors were male sex, heart rate and serum sodium concentration. CONCLUSIONS: SAPS II is a good prognostic tool for discriminating high-risk patient suitable for sub-intensive/intensive care units, whereas NEWS2 for discriminating low-risk patients for low-intensive units. Our results should be limited to cohorts with a high prevalence of elderly or comorbidities.

Effects of Antithrombotic Agents on Ophthalmological Outcomes, Cardiovascular Risk, and Mortality in Hypertensive Patients with Retinal Vein Occlusion: An Exploratory Retrospective Study.

Background and objectives: Because few data are available, the aim of this study is to analyze the effects of antithrombotic agents (ATAs) on visual function and long-term risk of cardiovascular events and mortality in hypertensive patients with retinal vein occlusion (RVO). Materials and methods: Hypertensive patients with RVO were consecutively selected from 2008 to 2012 and followed for a median of 8.7 years. Ophthalmologists evaluated and treated RVO complications, and best-corrected visual acuity (BCVA) was checked at each visit during the first one year of follow-up. Survival analysis was conducted on the rate of the composite endpoint of all-cause deaths or non-fatal cardiovascular events. Results: Retrospectively, we collected data from 80 patients (age 68 ± 12 years, 39 males). Central and branch RVO was present in 41 and 39 patients, respectively, and 56 patients started ATAs (50 antiplatelet drugs, 6 warfarin, and 2 low-molecular weight heparin). Average BCVA of the cohort did not change significantly during one-year of follow-up. The only predictor of BCVA was the baseline BCVA value. There was a reduction in proportion and severity of macular edema and an increase in the cumulative proportion of retinal vein patency reestablishment during the follow-up, independent of treatment. ATAs had no effects on one-year BCVA, intraocular complications, or the composite endpoint rate. Conclusions: In this exploratory study, ATAs had no effect on BCVA during the first one year of follow-up and on the composite endpoint during the long-term follow-up. Further prospective studies need to be conducted with an accurate standardization of the intraocular and antithrombotic treatment to define the positive or negative role of ATAs in hypertensive patients with RVO.

Atrial fibrillation and its complications in arterial hypertension: The potential preventive role of ω-3 polyunsaturated fatty acids.

Atrial fibrillation (AF) is the most common type of arrhythmia in the general population with a prevalence that reaches one third of patients with arterial hypertension. Several risk factors frequently associated with hypertension predispose the myocardium to AF by inducing atrial inflammation and fibrosis and altering atrial electrical and mechanical characteristics. AF influences the quality of life of hypertensive patients since it increases incidence of stroke and other thromboembolic events, and mortality. Polyunsaturated fatty acids of the ω-3 family (ω-3 PUFA) have been demonstrated to be beneficial in cardiovascular disease prevention by reducing plasma lipids and blood pressure levels and decreasing the risk of sudden death. These fatty acids can act as potent anti-inflammatory and anti-arrhythmic agents. Many studies have investigated a possible preventive effect of ω-3 PUFA on incident AF reporting contradictory results. This article overviews the evidence currently available on this important topic and provides some conclusive remarks on the possibility that these fatty acids could be beneficial in hypertensive patients.

Mineralocorticoid Receptor Blockers and Aldosterone to Renin Ratio: A Randomized Controlled Trial and Observational Data.

Current guidelines recommend to withdraw mineralocorticoid receptor (MR) blocker treatment for at least 4 weeks when measuring the aldosterone to renin ratio (ARR) as a screening test for primary aldosteronism (PA). We aimed to evaluate the effect of MR blocker treatment on ARR and its components, plasma aldosterone concentration (PAC), and direct renin concentration (DRC). First, we performed a post-hoc analysis of the effect of eplerenone on parathyroid hormone levels in primary hyperparathyroidism (EPATH) study, a randomized controlled trial (RCT) in 110 patients with primary hyperparathyroidism (pHPT). Patients were 1:1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or placebo for 8 weeks. Second, we measured the ARR in 4 PA patients from the Graz Endocrine Causes of Hypertension Study (GECOH) before and after MR blocker treatment. Ninety-seven participants completed the EPATH trial, and the mean treatment effect (95% confidence interval) for log(e)ARR was 0.08 (-0.32 to 0.48) ng/dl/µU/ml (p=0.694). The treatment effect was 0.71 (0.47 to 0.96; p<0.001) ng/dl for log(e)PAC and 0.64 (0.19 to 1.10; p=0.006) µU/ml for log(e)DRC, respectively. In the 4 PA patients, the ARR decreased from 11.24±3.58 at baseline to 2.70±1.03 (p=0.013) ng/dl/µU/ml after MR blocker treatment. In this study with limited sample size, MR blocker treatment did not significantly alter the ARR in pHPT patients but significantly reduced the ARR in PA patients. Diagnostic utility of ARR and its components for PA diagnostics under MR blocker treatment warrants further study.

The SPARTACUS Trial: Controversies and Unresolved Issues.

Adrenal vein sampling (AVS) is considered the gold standard for the differential diagnosis in patients with primary aldosteronism (PA). The distinction between unilateral and bilateral disease dictates the targeted therapeutic approach with surgery for aldosterone producing adenomas and medical therapy for patients with bilateral hyperplasia. Thereby, this diagnostic step is crucial in clinical care. As AVS is an invasive, not well standardized procedure that is restricted to few specialized centers, several attempts have been made to simplify diagnostic algorithms. In this clinical scenario, the recently published SPARTACUS trial aimed at answering the question whether AVS in fact is superior for differential diagnosis in comparison to imaging of the adrenal glands. In this multicenter study, patients were randomized to be treated according to AVS results or based on abdominal imaging only. Clinical outcome in both patient groups after one year was reported as not different. While the study results found broad interest, it also stirred considerable controversies. This review provides an overview on the different views regarding the outline of the SPARTACUS trial and the interpretation of its results.

Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial.

BACKGROUND: Primary hyperparathyroidism (pHPT) is associated with low-grade inflammation, left ventricular hypertrophy and increased cardiovascular mortality, but the association between inflammatory markers and parameters of adverse cardiac remodeling is unknown. We investigated the relationship between C-reactive protein (CRP), the essential amino acid tryptophan and its pro-inflammatory derivatives kynurenine and quinolinic acid (QUIN) with echocardiographic parameters. METHODS: Cross-sectional baseline data from the "Eplerenone in Primary Hyperparathyroidism" trial were analyzed. Patients with any acute illness were excluded. We assessed associations between CRP, serum levels of tryptophan, kynurenine and QUIN and left ventricular mass index (LVMI), left atrial volume index (LAVI) and E/e'. RESULTS: Among 136 subjects with pHPT (79% females), 100 (73%) had arterial hypertension and the prevalence of left ventricular hypertrophy was 52%. Multivariate linear regression analyses with LVMI, LAVI and E/e' as respective dependent variables, and C-reactive protein and tryptophan, kynurenine and QUIN as respective independent variables were performed. Analyses were adjusted for age, sex, blood pressure, parathyroid hormone, calcium and other cardiovascular risk factors. LVMI was independently associated with CRP (adjusted ß-coefficient=0.193, p=0.030) and QUIN (ß=0.270, p=0.007), but not kynurenine. LAVI was related with CRP (ß=0.315, p<0.001), kynurenine (ß=0.256, p=0.005) and QUIN (ß=0.213, p=0.044). E/e' was related with kynurenine (ß=0.221, p=0.022) and QUIN (ß=0.292, p=0.006). Tryptophan was not associated with any of the remodeling parameters. [Correction added after online publication (22 April 2017: The sentence "Among 136 subjects with pHPT (79% females), 100 (73%) had left ventricular hypertrophy." was corrected to "Among 136 subjects with pHPT (79% females), 100 (73%) had arterial hypertension and the prevalence of left ventricular hypertrophy was 52%."] Conclusions: Cardiac remodeling is common in pHPT and is associated with low-grade inflammation and activation of the tryptophan-kynurenine pathway. The potential role of kynurenine and QUIN as cardiovascular risk factors may be further investigated in future studies.

Long-Term Renal and Cardiac Outcomes after Stenting in Patients with Resistant Hypertension and Atherosclerotic Renal Artery Stenosis.

BACKGROUND/AIMS: Atherosclerotic renal artery stenosis (ARAS) is frequently detected in patients with resistant hypertension (RHTN), but the evidence supporting the utility of renal revascularization in these patients is limited. This prospective, observational study investigates the outcomes of renal stenting in patients with RHTN and hemodynamically significant ARAS. METHODS: Fifty-four patients with RHTN were selected because of angiographic evidence of ARAS >70% and were followed for 4 years after renal stenting. Renal function and echocardiographic variables were assessed at baseline and during follow-up. RESULTS: Blood pressure decreased rapidly after renal stenting and was normalized in 67% of patients at six months, with significant reduction in the number of antihypertensive drugs. Creatinine clearance increased in 39% of patients, decreased in 52%, and remained stable in the remaining 9%, with an average value that had a nonsignificant decrease during follow-up. Urinary albumin excretion did not change throughout the study. After 4 years, left ventricular (LV) wall thickness and concentric geometry decreased significantly and variables of LV diastolic function improved. CONCLUSION: In patients with RHTN, stenting of hemodynamically significant ARAS decreases blood pressure, preserves renal function in a substantial proportion of patients, and improves LV structure and function, suggesting the opportunity for timely identification of ARAS in these patients.

Decreased fibrinolytic activity is associated with carotid artery stiffening in arterial hypertension.

BACKGROUND: A prothrombotic state is associated with the presence and severity of organ damage in hypertensive patients. In these patients, evidence of subclinical carotid functional changes anticipates major cardiovascular events. The aim of this study was to investigate the association of hemostatic markers with carotid artery stiffness in hypertension. MATERIALS AND METHODS: In 116 untreated essential hypertensive patients recruited at a referral center in the University of Udine, we assessed common carotid artery stiffness by B-mode ultrasonography and measured plasma fibrinogen, D-dimer, plasminogen activator inhibitor-1 (PAI-1), and homocysteine by the currently available methods. For statistical reasons, the patients were divided according to the median value of each index of carotid stiffness, and continuous variables were further analyzed by univariate correlation and stepwise multivariate regression analysis. RESULTS: PAI-1 levels were significantly higher in patients with low coefficient of distensibility (P = 0.018) and high Young's elastic modulus (P = 0.012), whereas no association of fibrinogen, D-dimer, and homocysteine levels was observed with carotid coefficient of distensibility, Young's elastic modulus, and ß-stiffness. On univariate analysis, Young's elastic modulus was significantly and positively correlated with PAI-1 levels (r = 0.286, P = 0.002), a correlation that on multivariate regression resulted to be independent of other confounders (ß = 0.289, P = 0.028). CONCLUSION: An independent association of plasma PAI-1 levels with carotid artery stiffness suggests a possible contribution of decreased fibrinolytic activity to the early functional abnormalities of arterial vessels in hypertensive patients. This contribution might be relevant for subsequent development of hypertension-related cardiovascular complications.

Intrarenal Vascular Resistance is Associated With a Prothrombotic State in Hypertensive Patients.

BACKGROUND/AIMS: Hypertensive nephroangiosclerosis is associated with progressive increase of intrarenal vascular resistance. In addition to blood pressure, other factors can contribute to hypertensive renal damage including a prothrombotic state. We investigated the relationship between hemostatic markers and intrarenal vascular resistance in hypertension. METHODS: In 115 untreated, nondiabetic, hypertensive subjects free of cardiovascular complications and advanced renal function impairment, we measured 24-hour creatinine clearance (GFR) and urinary albumin excretion (UAE), fasting plasma glucose, HOMA-index, and plasma levels of fibrinogen, D-dimer, prothrombin fragment 1+2, plasminogen activator inhibitor-1, homocysteine, and lipoprotein(a). In all patients, measurement of intrarenal resistance was obtained by renal Doppler ultrasound with calculation of the renal resistance index (RI). RESULTS: Patients in the highest tertile of RI were older and had greater body mass index, pulse pressure, fibrinogen, and D-dimer levels and lower GFR than patients in the lowest RI tertile. RI was directly correlated with age, pulse pressure, HOMA-index, UAE, D-dimer, and inversely with GFR. On multivariate analysis, RRI was independently associated with age, GFR, and plasma D-dimer. CONCLUSIONS: A prothrombotic state is associated with increased intrarenal vascular resistance in nondiabetic hypertensive patients and might contribute to the early stages of hypertensive renal disease.

Plasma lipoprotein(a) levels and atherosclerotic renal artery stenosis in hypertensive patients.

BACKGROUND/AIMS: The contribution of emergent cardiovascular risk factors to atherosclerotic renal artery stenosis (ARAS) is debated. We investigated the relationship of lipoprotein(a) and prothrombotic factors with ARAS in hypertension. METHODS: In 50 hypertensive patients with angiographic evidence of ARAS and 58 hypertensive patients who had comparable cardiovascular risk factor burden but no evidence of renovascular disease, we measured renal function, lipoprotein(a), homocysteine, and hemostatic-fibrinolytic markers. RESULTS: Patients with ARAS were more frequently smokers and had longer duration of hypertension, heavier antihypertensive treatment, and worse renal function than controls. Lipoprotein(a) was higher in patients with ARAS than controls, whereas no differences were found in homocysteine and all hemostatic variables. Multivariate analysis showed that lipoprotein(a) was associated with ARAS independent of other confounders including renal function and history of coronary heart, cerebrovascular, and peripheral artery disease. CONCLUSION: Lipoprotein(a) might contribute to the development of ARAS and detection of elevated levels of this lipoprotein could raise the suspicion of renovascular disease in patients with high blood pressure.

Uricaemia and left ventricular mass in hypertensive patients.

BACKGROUND: Both hyperuricaemia and left ventricular (LV) hypertrophy are associated with the metabolic syndrome and increased cardiovascular risk. The relationship between uric acid levels and left ventricular mass in hypertension, however, is unclear. In this study, we have investigated this relationship in hypertensive patients without the metabolic syndrome. MATERIALS AND METHODS: In a cross-sectional study, 367 nondiabetic, essential hypertensive patients (age 52 ± 14; 194 males and 173 females) free of clinically relevant cardiovascular complications and without the metabolic syndrome were consecutively recruited at a university hypertension clinic. In these patients, we measured plasma levels of uric acid, lipids, glucose and insulin at fast and after an oral glucose load (OGTT), renal function and performed both conventional and tissue Doppler echocardiography. RESULTS: Hypertensive patients with LV hypertrophy had higher uric acid levels and greater prevalence of hyperuricemia than patients with normal left ventricular mass. Uric acid levels were directly related with fasting and post-OGTT plasma insulin and with the HOMA index and inversely with 24-h creatinine clearance. Uric acid was also significantly and directly related with the left ventricular mass and multivariate regression analysis showed that this relationship was independent from components of the metabolic syndrome and renal function in women, but not in men. CONCLUSIONS: Elevated uric acid levels are independently related to the left ventricular mass in hypertensive women without the metabolic syndrome. In these patients with a low cardiovascular risk profile, uric acid might contribute to the development of subclinical cardiac damage.

Cortisol secretion and abnormalities of glucose metabolism in nondiabetic patients with hypertension.

OBJECTIVE: Glycometabolic changes are associated with hypercortisolism in Cushing's syndrome. Because impaired glucose tolerance (IGT) and insulin resistance are frequently detected in patients with essential hypertension, we hypothesized that in these patients, early glycometabolic abnormalities might be related to differences in regulation of cortisol secretion. METHODS: In a cross-sectional study, we included 155 nondiabetic, essential hypertensive patients who were free of organ complications. The homeostasis model assessment (HOMA) index and the area under the curve of plasma glucose (AUC-glucose) and insulin (AUC-insulin) concentration following an oral glucose tolerance test were measured, together with daily plasma cortisol (8 a.m., 3 p.m. and 12 a.m.; AUC-cortisol) and 8 a.m. cortisol after 1 mg overnight dexamethasone suppression test (DST). RESULTS: IGT was present in 27% of patients who were older and had higher BMI, plasma triglycerides and uric acid, AUC-cortisol and DST-cortisol, and lower HDL-cholesterol. Frequency of IGT increased progressively across tertiles of DST-cortisol, together with levels of glycated hemoglobin, fasting insulin and C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. AUC-cortisol and DST-cortisol were directly correlated with insulin, C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. Multivariate regression analysis showed that DST-cortisol was directly and independently correlated with HOMA index, AUC-glucose, and AUC-insulin. In a logistic regression model, both AUC-cortisol and DST-cortisol independently predicted IGT. CONCLUSION: Daily cortisol and cortisol response to DST are independent determinants of IGT and insulin resistance in nondiabetic patients with hypertension, suggesting that even subtle differences in regulation of cortisol secretion might increase the risk of these patients to develop diabetes.

Daytime plasma cortisol and cortisol response to dexamethasone suppression are associated with a prothrombotic state in hypertension.

Background and aims: A prothrombotic state was demonstrated in patients with Cushing's syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension. Methods: In 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol). Results: Plasma levels of D-dimer (D-dim), prothrombin fragment 1 + 2 (F1 + 2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1 + 2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1 + 2, and vWF independently of age, body mass index, blood pressure, and renal function. Conclusion: Greater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications.

Aldosterone, organ damage and dietary salt.

Long-term exposure to elevated aldosterone levels or activation of the mineralocorticoid receptors results in cardiac, vascular and renal tissue injury with mechanisms that are independent of blood pressure levels. This evidence has been obtained in experiments carried out in hypertensive animal models, and clinical studies involving patients with heart failure, essential hypertension and primary aldosteronism. Animal studies have shown that aldosterone causes cardiovascular and renal tissue damage only in the context of an inappropriate salt status. It has also been suggested that some of the untoward effects of high-salt intake might depend on activation of mineralocorticoid receptors resulting from increased generation of reactive oxygen species and changes in the intracellular redox potential. Although the interaction between dietary salt intake and circulating aldosterone in causing organ damage has received robust support from the results of animal experiments, the evidence of such interaction in the clinical setting is only preliminary and will require further investigation in appropriately designed studies.

Effects of Monacolin K in Nondiabetic Patients with NAFLD: A Pilot Study.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition with significant risk of progression to steatohepatitis and cirrhosis. Therapeutic strategies in NAFLD include lifestyle changes mainly related to dietary interventions and use of drugs or nutritional components that could improve plasma lipid profiles and insulin sensitivity and decrease the local inflammatory response. In this study, we tested the effects of monacolin K, an inhibitor of HMCoA reductase. In a prospective, uncontrolled, open study, we treated 24 patients with NAFLD and mild hypercholesterolemia with 10 mg/day of monacolin K. At baseline and after 26 weeks, we measured in plasma liver tests, lipids, malondialdehyde, and oxidized glutathione, and assessed biochemical steatosis scores, liver elastography, and body composition with bioimpedance analysis. Monacolin K significantly reduced plasma alanine aminotransferase, cholesterol, triglycerides and the homeostatic model assessment (HOMA) index that indicated improved insulin sensitivity. No significant changes were found in body fat mass and visceral fat, nor in liver elastography, while the fatty liver index (FLI) was significantly decreased. Plasma levels of both malondialdehyde and oxidized glutathione were markedly reduced by monacolin K treatment, suggesting a reduction in oxidative stress and lipid peroxidation. In summary, this pilot study suggests possible benefits of monacolin K use in NAFLD patients that could be linked to a reduction in oxidative stress. This hypothesis should be further investigated in future studies.