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Preeclampsia (PE) is associated with persistent cardiac abnormalities and a high cardiovascular risk during the woman life. Early onset PE presenting before the 34 th gestational week is a more severe form of disease, but its relevance on cardiac abnormalities is unknown. The aim of this study was to assess cardiac structure and function in women with PE without preexistent hypertension. One month after delivery, the clinical and echocardiographic variables of 65 preeclamptic women (age 36±6 y), 37% of which with early PE, was compared with a group of 30 normotensive (age 37±6 y), 16 hypertensive (age 40±5 y) nonpregnant women, and 6 women with normal pregnancy (age 36±5 y) who were matched for age and height. Despite comparable antihypertensive treatment, women with early PE had lower 24-hour average systolic and diastolic blood pressure than those with late PE (125±11 Vs 136±15). Left ventricle (LV) relative wall thickness was significantly greater in women with early PE (0.36±0.06) than in those with late PE (0.31±0.07; p

Objectives: Recent studies suggest an association between vitamin D deficiency and prevalence of cardiovascular disease in the general population. However, the evidence of a relationship between vitamin D status and vascular functional changes in hypertension is currently controversial. We aimed to investigate if the presence of low serum vitamin D levels is associated with an increased arterial stiffness in essential hypertension. Design and Method: In 151 essential hypertensive patients (53±13 y, 71 males) we measured serum 25(OH)-vitamin D levels and performed a carotid ultrasound examination to determine variables of carotid stiffness, such as distensibility, compliance, Young elastic modulus and beta-stiffness. Furthermore, in a subgroup of 86 subjects we evaluated the augmentation index and the pulse wave velocity. The patients were subdivided into two groups according to the 25(OH)-vitamin D levels, lower or higher than 30 nmol/L. Results: A plasma vitamin D level lower than 30 nmol/L was found in 83 (55%) of 151 patients. Patients with low vitamin D levels were significantly older than those with a normal value of serum vitamin D. No significant differences in carotid artery distensibility, compliance, Young elastic modulus, and beta-stiffness were observed between patients with plasma vitamin D below or above 30 nmol/L. Also, the augmentation index and the pulse wave velocity were comparable in hypertensive patients with lower or higher plasma vitamin D levels. Conclusions: This study does not support the hypothesis of an association between vitamin D deficiency and functional vascular changes in hypertensive patients.

Objective: In patients with primary hypertension, plasma aldosterone levels are significantly decreased by an intravenous saline load (IVSL), but this response is variable among patients and related to the ability of salt to modulate aldosterone production. Previous studies have reported that activity of the renin-angiotensin-aldosterone system is related with age. The aim of this study was to investigate whether age might affect the aldosterone response to an IVSL. Design and Method: In 124 hypertensive patients (48±13 y, 71 males) who were washed-out of antihypertensive drugs for 2 weeks, we measured renin and PA levels before and after an IVSL (2 lt. saline in 4 h). In all patients secondary causes of hypertension were excluded. For statistical purposes patients were subdivided into two groups based on age (< or > 60 y). Results: Twenty-three of 124 patients (18%) were had 60 y of age or more (range 61-77) and the remaining were younger than 60 y (19-60 y). No differences were found between the two groups for gender, body mass index, serum potassium and creatinine clearance. Urinary sodium excretion was comparable in patients older (159±83) or younger (159±66) than 60 y. Baseline PA (76 [49-121] pg/ml) and renin (5.0 [1.9-9.8] mcIU/ml) levels were significantly lower in patients older than 60 y than in those younger than 60 y (115 [77-162] pg/ml, P=0.019; 10.7 [5.1-20.8] mcIU/ml, P=0.026). As expected IVSL decreased significantly (P Conclusions: PA levels are lower in hypertensive patients older than 60 y. This difference becomes more relevant after IVSL suggesting greater response of the renin-angiotensin system to volume expansion. This should be taken into account in the diagnostic work-out of hypertensive patients.

Objectives:Cushing syndrome and subclinical hypercortisolism are associated with changes in left ventricular (LV) structure. No data are available on the relationship between cortisol production and LV mass and geometry in essential hypertension (EH).Methods:In 103 EH patients, we evaluated clinical

In experimental animal models, exogenous aldosterone excess has been linked to the progression of renal disease. However, the evidence of an increased risk of renal damage in patients affected by primary aldosteronism remains controversial. We aimed at evaluating the association between primary aldosteronism and renal damage through a meta-analysis.We performed a quantitative review of studies evaluating parameters of renal function in patients affected by primary aldosteronism compared with hypertensive patients without primary aldosteronism and in patients affected by primary aldosteronism before and after treatment. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1960 up to April 2019.Forty-six studies including 6056 patients with primary aldosteronism and 9733 patients affected by arterial hypertension without primary aldosteronism were included. After 8.5 years from hypertension diagnosis, patients with primary aldosteronism had an increased estimated glomerular filtration rate (eGFR) compared with hypertensive patients without primary aldosteronism [by 3.37 ml/min IQR (0.82-5.93)] and a more severe albuminuria [standard mean difference 0.55 (0.19-0.91)], resulting into an association with microalbuminuria [odds ratio (OR) 2.09 (1.40; 3.12)] and proteinuria [OR 2.68 (1.89;3.79)]. Following primary aldosteronism treatment, after a median follow-up of 12 months, a reduction in eGFR was observed [by -10.69 ml/min (-13.23; -8.16)], consistent in both medically and surgically treated patients. Similarly, a reduction in albumin excretion and an increase in serum creatinine were observed after treatment.Patients affected by primary aldosteronism, compared with patients affected by arterial hypertension without primary aldosteronism, display a more pronounced target organ damage, which can be mitigated by the specific treatment.

Mineralocorticoid receptor antagonists (MRAs) are commonly used to reduce blood pressure, left-ventricular hypertrophy, and urinary albumin excretion in patients with essential hypertension or primary aldosteronism. Effects of MRAs on hypertensive organ damage seem to occur beyond what is expected from the mere reduction of blood pressure. This suggests that activation of the mineralocorticoid receptor plays a central role in the development of cardiac and renal abnormalities in hypertensive patients. However, broad use of classic MRAs such as spironolactone has been limited by significant incidence of gynecomastia and other sex-related adverse effects. To overcome these problems, new aldosterone blockers have been developed with different strategies that include use of nonsteroidal MRAs and inhibition of aldosterone synthesis. Both strategies have been designed to avoid the steroid receptor cross-reactivity of classic MRAs that accounts for most adverse effects. Moreover, inhibition of aldosterone synthesis could have an additional benefit due to blockade of the mineralocorticoid receptor-independent pathways that might account for some of the untoward effects of aldosterone. The new aldosterone blockers are currently having extensive preclinical evaluation, and one of these compounds has passed phase 2 trials showing promising results in patients with primary hypertension and primary aldosteronism. This narrative review summarizes the knowledge on the use of classic MRAs in hypertension and covers the evidence currently available on new aldosterone blockers.

Sardinia is an island community of 1.6 million people. There are also about 3.5 million sheep and one hundred thousand cattle in which Johne's disease and Mycobacterium avium subspecies paratuberculosis infection are endemic. The present study was designed to determine what proportion of people in Sardinia attending for ileocolonoscopy with or without Crohn's disease were infected with this pathogen.Mycobacterium avium subspecies paratuberculosis was detected by IS900 PCR on DNA extracts of fresh intestinal mucosal biopsies as well as by isolation in culture using supplemented MGIT media followed by PCR with amplicon sequencing.Twenty five patients (83.3%) with Crohn's disease and 3 control patients (10.3%) were IS900 PCR positive (p = 0.000001; Odds ratio 43.3). Mycobacterium avium subspecies paratuberculosis grew in cultures from 19 Crohn's patients (63.3%) and from 3 control patients (10.3%) (p = 0.00001; Odds ratio 14.9). All patients positive by culture had previously been positive by PCR. Mycobacterium avium subspecies paratuberculosis first appeared in the liquid cultures in a Ziehl Neelsen (ZN) staining negative form and partially reverted through a rhodamine-auramine positive staining form to the classical ZN positive form. This resulted in a stable mixed culture of all 3 forms illustrating the phenotypic versatility of these complex chronic enteric pathogens.Mycobacterium avium subspecies paratuberculosis was detected in the majority of Sardinian Crohn's disease patients. The finding of the organism colonizing a proportion of people without Crohn's disease is consistent with what occurs in other conditions caused by a primary bacterial pathogen in susceptible hosts.

Objectives To evaluate the relationships between alcohol intake and serum lipoprotein(a) [Lp(a)], a powerful predictor of organ damage, in patients with essential hypertension with a wide range of alcohol intake, and to investigate whether the association between alcohol intake and serum Lp(a) concentrations occurs over the entire spectrum of apo(a) phenotypes. Design Cross-sectional study of a case series. Setting University medical centre. Patients Four hundred and two patients with untreated essential hypertension recruited at a hypertension clinic. Main outcome measures Serum Lp(a) concentrations, apo(a) isoforms, alcohol consumption, smoking habits and cardiovascular status. Results No difference in Lp(a) concentrations was observed between teetotalers and occasional drinkers. Light drinkers (1–20 g/day ethanol), moderate drinkers (21–50 g/day), and heavy drinkers (>50 g/day) had, respectively, 21, 26 and 57% lower median Lp(a) concentrations than teetotalers and occasional drinkers. Similar findings were obtained when male and female patients were analysed separately. Log Lp(a) concentrations were inversely and independently correlated with alcohol consumption in both men and women with hypertension. The frequency distributions of apo(a) isoforms and liver function parameters were comparable across the different alcohol intake groups. Patients with evidence of cardiovascular damage had greater concentrations of serum Lp(a) and higher frequency of low-molecular weight apo(a) isoforms as compared with patients without such evidence. Conclusions Serum Lp(a) is inversely and dose-dependently related with alcohol intake in patients with hypertension, and this relationship is independent of the size distribution of apo(a) isoforms. Reduction of Lp(a) concentrations by regular consumption of alcohol might favourably affect the atherosclerotic risk profile of patients with hypertension and thereby decrease cardiovascular morbidity.

Experimental nephrotic syndrome is characterized by abnormal sodium metabolism, reflected in a blunted natriuretic response both to volume expansion and to infused atrial natriuretic peptide (ANP). The studies presented here examined the relationships among plasma ANP concentration and urinary sodium (VNaV) and cyclic GMP excretion (UcGMPV) in vivo, and the responsiveness of isolated glomeruil and inner medullary collecting duct (IMCD) cells to ANP and urodilatin (renal natriuretic peptide; RNP) in vitro in rats with Heymann nephritis, an immunologically mediated model of nephrotic syndrome. Nine to 14 days after Ip injection of anti-Fx1A antiserum, rats were proteinuric and had a blunted natriuretic response to intravenous infusion of isotonic saline (2% body weight, given over 5 min). Thirty min after the onset of the infusion, plasma ANP concentration was increased to the same extent in both normal and nephritic rats, compared with their respective hydropenic controls. Despite this increase, UcGMPV was significantly less in nephritic rats after the saline infusion. Accumulation of cGMP by isolated glomeruil and IMCD cells from nephritic rats after incubation with ANP and RNP was also significantly reduced, compared with normal rats. This difference was not related to differences in either density or affinity of renal ANP receptors, but was abolished when accumulation of cGMP was measured in the presence of 10(-3) M isobutylmethylxanthine or Zaprinast, two different inhibitors of cyclic nucleotide phosphodiesterases (PDE). Infusion of Zaprinast into one renal artery in nephritic rats normalized both the natriuretic response to volume expansion and the increase in UcGMPV from the infused, but not the contralateral, kidney. Furthermore, cGMP-PDE activity was increased in IMCD cell homogenates from nephritic compared with normal rats (388 +/- 32 versus 198 +/- 93 pmol/min per mg protein, P0.03). These results indicate that blunted volume expansion natriuresis accompanied by cellular resistance to ANP in vitro occurs in an immunologic model of renal injury. The resistance is not related to an alteration in ANP release or binding to its renal receptors, but is suppressed by PDE inhibitors and is associated with increased renal cGMP. PDE activity, thus suggesting that enhanced cGMP-PDE activity may account for resistance to the natriuretic actions of ANP observed in vivo. This defect may represent the intrinsic sodium transport abnormality linked to sodium retention in nephrotic syndrome.

To the Editor: In their prospective study, Gaddam et al1 have examined the effects of spironolactone on cardiac structure in 34 patients with resistant hypertension who were separated according to their plasma aldosterone levels. At baseline, cardiac volume overload was detected in patients with higher aldosterone levels that was significantly and rapidly reduced by spironolactone, whereas left ventricular (LV) mass was comparable at baseline and decreased significantly after treatment in both patients with higher and lower plasma aldosterone. Detection of comparable baseline LV mass even in the presence of significant volume overload is difficult to explain. As …

This study was designed to investigate the adherence of corneal isolates of S. epidermidis, Serratia marcescens , and Pseudomonas aeruginosa to the widely used AcrySof IOL (model MA60BM, Alcon Surgical).