Increased Microalbuminuria Risk in Male Cigarette Smokers: Results from the “Olivetti Heart Study” after 8 Years Follow-Up

Background/Aims: Association between cigarette smoke and albuminuria (UA) was already demonstrated in cross-sectional studies and in selected population samples (i.e diabetic patients). This study aims to evaluate, prospectively, the relationship between cigarette smoke and UA in a male adult population sample, with basal normal kidney function, participating in the Olivetti Heart Study (OHS). Methods: Among 994 participants, examined in both 1994-95 and 2002-04, were selected those resulted in both visits smokers (n=221) and non-smokers (n=416) and with basal normal kidney function (GFR> 60 mL/min) and basal albumin/creatinine ratio (ACR< 30 mg/g). Results: At baseline, the prevalence of hypertension was 41%, diabetes affected 6.3% and obesity 17% of the whole sample. Smokers showed statistically significant lower levels of systolic (SBP) and diastolic blood pressure (DBP) and BMI (p< 0.001) compared to non-smokers. There were not basal differences in UA, GFR and metabolic profile. However, at follow-up examination, smokers showed a statistically significant increase in SBP and DBP (p< 0.05), but not in GFR and BMI. Moreover, smokers showed a higher risk compared to non-smokers to be in the higher median levels group of UA (OR: 2.17, C.I.95%: 1.51-3.13; p < 0.001), even after correction for major confounding factors. Further adjustment for basal antihypertensive and hypoglycemic treatment did not change these patterns of association. Conclusion: In a selected male adult population sample, cigarette smoke was independently associated with the development of higher levels of albuminuria over time

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Eosinophilic perimyocarditis associated with eosinophilic granulomatosis with polyangiitis: a case report

Background Eosinophilic myocarditis (EM) is a rare and potentially life-threatening form of myocarditis, frequently (but not always) associated with eosinophilia, and presents with acute chest pain, or signs and symptoms of acute or chronic heart failure. Eosinophilic myocarditis has various aetiologies, including eosinophilic granulomatosis with polyangiitis (EGPA). Case summary A 52-year-old female with a long-standing history of asthma, acral paraesthesia, subcutaneous nodules, and recurrent chest pain treated with anti-inflammatory drugs was admitted to our hospital with chest pain, repolarization disturbances, eosinophilia, and increased troponin levels. After an initial evaluation by coronary angiography, echocardiography and cardiac magnetic resonance, a definitive diagnosis of EM was made with the help of an endomyocardial biopsy. The aetiological diagnosis of EM as a manifestation of tissue involvement in EGPA was concluded after ruling out other possible causes of eosinophilia and with the help of other diagnostic criteria for EGPA (asthma, eosinophilia, and neuropathy). Therefore, we started with a high dosage of glucocorticoids, and attained relief of symptoms and normalization of eosinophilic count after a few days. Discussion In cases of myocarditis (particularly if associated with eosinophilia), EM is a manifestation of EGPA and should be considered for a prompt differential diagnosis. Endomyocardial biopsy represents the gold standard for the diagnosis of EM. The mainstay of therapy for EM is immunosuppressive drugs to help prevent its evolution to a fulminant form and chronic progression towards restrictive cardiomyopathy

Circulating leptin levels predict the decline in renal function with age in a sample of adult men (The Olivetti Heart Study)

Leptin (LPT) is associated with a number of cardiovascular risk factors, such as high blood pressure (BP), insulin resistance and excess in body weight. Some studies find an unfavorable cross-sectional association between LPT and renal disease, in particular in patients with already known kidney dysfunction. There are few data on the relationship between LPT and changes in renal function over time in subjects without evidence of kidney dysfunction. Hence, the aim of this study is to estimate the predictive role of LPT on the decline in renal function occurring in an 8-year follow-up observation of a sample of adult apparently healthy men (The Olivetti Heart Study). The study includes 319 untreated normotensive and nondiabetic men without clinical evidence of renal dysfunction (creatinine clearance-CrCl > 60 mL/min/1.73 m2) at baseline. At baseline, LPT is significantly and positively associated with BMI, abdominal circumference, BP and Homa index, no relationship is found with CrCl. At the end of the 8-year follow-up, a significant association is detected between baseline LPT and changes occurring in BP. Moreover, an inverse correlation with changes in CrCl is found (r = - 0.12). This unfavorable relationship between baseline LPT and decline in renal function is also confirmed in the multivariate analyses, after adjustment for all potential confounders (R2 = 0.42, p < 0.01). The results of this prospective investigation suggest a predictive role of circulating LPT levels on decline in renal function over time, independently of main potential confounders, in normotensive and nondiabetic men with normal renal function at baseline

Renal potassium handling in carriers of the Gly40Ser mutation of the glucagon receptor suggests a role for glucagon in potassium homeostasis

International audiencePlasma potassium concentration (PK ) is tightly regulated. Insulin is known to favor potassium entry into cells. But how potassium leaves the cells later on is not often considered. Previous studies in rats showed that glucagon infusion increased urinary potassium excretion dose-dependently and reversibly. This prompted us to investigate the possible influence of glucagon on potassium handling in humans. We took advantage of the Gly40Ser mutation of the glucagon receptor (GR) that results in a partial loss of function of the GR. In the Olivetti cohort (male workers), 25 subjects who carried this mutation were matched 1:4 to 100 noncarriers for age and weight. Estimated osmolarity of serum and 24-h urine (Sosm and Uosm, respectively) was calculated from the concentrations of the main solutes: [(Na+K)*2 + urea (+glucose for serum)]. Transtubular potassium gradient (TTKG), reflecting the intensity of K secretion in the distal nephron, was calculated as [(urine K/serum K)(Uosm /Sosm )]. There was no significant difference in serum K, or 24-h urine urea, Na and K excretion rates. But urine K concentration was significantly lower in carriers than in noncarriers. Means (interquartile range): 38 (34-43) versus 47 (43-51) mmol/L, P = 0.030. TTKG was also significantly lower in carriers: 4.2 (3.9-4.6) versus 5.0 (4.7-5.2), P = 0.015. This difference remained statistically significant after adjustments for serum insulin and 24-h Na and urea excretions. These results in humans suggest that glucagon stimulates K secretion in the distal nephron. Thus, in conjunction with insulin, glucagon may also participate in K homeostasis by promoting renal K excretion