The coronavirus disease 2019 (COVID-19) pandemic remains an unbeaten enemy. Unfortunately, no targeted treatment option is available. Patients with type 2 diabetes mellitus (T2DM) have increased odds ...for severe or fatal disease, as demonstrated in recent observational studies. There is an ongoing discussion regarding the impact of different antidiabetic drug classes on outcomes of interest among affected subjects. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been placed at the epicenter, since the DPP-4 enzyme seems to be implicated in the disease pathogenesis. Herein we present an updated meta-analysis of observational studies addressing the risk of COVID-19 death among patients with T2DM on prior DPP-4 inhibitor treatment. We pooled data from 10 observational studies, showing that DPP-4 inhibitors produce a non-significant decrease in the risk for COVID-19-related death. However, when administered in the inpatient setting, DPP-4 inhibitors decrease the risk for COVID-19-related death by 50%. Ongoing randomized controlled trials will shed further light.
Summary Background Results of several studies published since 1999 suggest that primary hyperaldosteronism (also known as Conn's syndrome) affects more than 10% of people with hypertension; however, ...such a high prevalence has also been disputed. Experts generally agree that resistant hypertension has the highest prevalence of primary hyperaldosteronism, on the basis of small studies. We aimed to assess the prevalence of primary hyperaldosteronism in a large group of patients with resistant hypertension. Methods Patients with resistant hypertension (blood pressure >140/90 mm Hg despite a three drug regimen, including a diuretic) who attended our outpatient clinic were assessed for primary hyperaldosteronism. Serum aldosterone and plasma renin activity were determined and their ratio was calculated. Patients with a positive test (ratio >65·16 and aldosterone concentrations >416 pmol/L) underwent salt suppression tests with intravenous saline and fludrocortisone. Diagnosis of primary hyperaldosteronism was further confirmed by the response to treatment with spironolactone. Findings Over 20 years, we studied 1616 patients with resistant hypertension. 338 patients (20·9%) had a ratio of more than 65·16 and aldosterone concentrations of more than 416 pmol/L. On the basis of salt suppression tests, 182 (11·3%) patients had primary hyperaldosteronism, and response to spironolactone treatment further confirmed this diagnosis. Hypokalaemia was seen only in 83 patients with primary hyperaldosteronism (45·6%). Interpretation Although the prevalence of primary hyperaldosteronism in patients with resistant hypertension was high, it was substantially lower than previously reported. On the basis of this finding, we could assume that the prevalence of primary hyperaldosteronism in the general unselected hypertensive population is much lower than currently reported. Thus, the notion of an epidemic of primary hyperaldosteronism is not supported. Funding None.
Non-alcoholic fatty liver disease (NAFLD) is considered to be an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a benign clinical course without excess mortality. ...In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis (NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease (CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness (AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis (mainly by simple non-invasive tests), CKD, and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.
Sexual dysfunction is currently considered a serious quality-of-life-related health problem, exerting a major impact on patients' and their sexual partners' life. Available data indicate that ...essential hypertension is a risk factor for sexual dysfunction, as male and female sexual dysfunction is more prevalent in hypertensive patients than normotensive individuals. Several mechanisms have been implicated in the pathogenesis of sexual dysfunction in hypertensive patients, and major determinants include severity and duration of hypertension, age, and antihypertensive therapy. Female sexual dysfunction, although more frequent than its male counterpart, remains largely under-recognized. Older antihypertensive drugs (diuretics, beta-blockers, centrally acting) exert negative results, whereas newer drugs have either neutral (calcium antagonists, angiotensin-converting enzyme inhibitors) or beneficial effects (angiotensin receptor blockers). Erectile dysfunction is related to ischemic heart disease and might be an 'early therapeutic window' of asymptomatic coronary artery disease. It seems of utmost importance for every physician treating hypertensive patients to become familiar with sexual dysfunction (through better education and specific seminars) for the proper management of these patients.
Summary Background Statins are commonly prescribed for management of dyslipidaemia and cardiovascular disease. Increased fitness is also associated with low mortality and is recommended as an ...essential part of promoting health. However, little information exists about the combined effects of fitness and statin treatment on all-cause mortality. We assessed the combined effects of statin treatment and fitness on all-cause mortality risk. Methods In this prospective cohort study, we included dyslipidaemic veterans from Veterans Affairs Medical Centers in Palo Alto, CA, and Washington DC, USA, who had had an exercise tolerance test between 1986, and 2011. We assigned participants to one of four fitness categories based on peak metabolic equivalents (MET) achieved during exercise test and eight categories based on fitness status and statin treatment. The primary endpoint was all-cause mortality adjusted for age, body-mass index, ethnic origin, sex, history of cardiovascular disease, cardiovascular drugs, and cardiovascular risk factors. We assessed mortality from Veteran's Affairs’ records on Dec 31, 2011. We compared groups with Cox proportional hazard model. Findings We assessed 10 043 participants (mean age 58·8 years, SD 10·9 years). During a median follow-up of 10·0 years (IQR 6·0–14·2), 2318 patients died, with an average yearly mortality rate of 22 deaths per 1000 person-years. Mortality risk was 18·5% (935/5046) in people taking statins versus 27·7% (1386/4997) in those not taking statins (p<0·0001). In patients who took statins, mortality risk decreased as fitness increased; for highly fit individuals (>9 MET; n=694), the hazard ratio (HR) was 0·30 (95% CI 0·21–0·41; p<0·0001) compared with least fit (≤5 METs) patients (HR 1; n=1060). For those not treated with statins, the HR for least fit participants (n=1024) was 1·35 (95% CI 1·17–1·54; p<0·0001) and progressively decreased to 0·53 (95% CI 0·44–0·65; p<0·0001) for those in the highest fitness category (n=1498). Interpretation Statin treatment and increased fitness are independently associated with low mortality among dyslipidaemic individuals. The combination of statin treatment and increased fitness resulted in substantially lower mortality risk than either alone, reinforcing the importance of physical activity for individuals with dyslipidaemia. Funding None.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease (30% of the general population) and up to 40% of cases advance to the more severe form of the disease: nonalcoholic ...steatohepatitis (NASH), which is causally related to cirrhosis and cardiovascular disease (CVD). There is no generally accepted effective treatment for NAFLD/NASH. The joint guidelines of the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD) and the European Association for the Study of Obesity (EASO) suggest the "off label" use of pioglitazone in patients without type 2 diabetes mellitus (T2DM) and pioglitazone in subjects with T2DM or vitamin E or their combination for the treatment of NASH; however pioglitazone has considerable limitations: weight gain, bone fractures in women, and heart failure. The aim of this narrative review is to assess the existing evidence supporting statin use for the treatment of NASH and the reduction of the high CVD risk of these patients. Animal data suggest that there is some benefit from statin use in liver histology in models of NASH. In humans, 3 post hoc analyses of randomised controlled trials (n=1,600, n=1,123, n=8,864) suggest that the use of atorvastatin (even in 80 mg/day) has a beneficial effect on NAFLD/NASH, in terms of liver enzyme reduction and ultrasonographic amelioration. Moreover, and most importantly, statin treatment halved CVD morbidity and mortality in statin-treated NAFLD/NASH patients compared with statin-treated participants with normal liver structure and function and reduced by 2/3rds CVD events in comparison with NAFLD/NASH patients that were not on a statin (90% of this population is not on statins because of the unjustified fear for liver damage). Three biopsy studies (n=20, n=107 and n=356) showed that statin treatment had a protective effect on steatosis, steatohepatitis and fibrosis. Data suggest that statin treatment in humans substantially improve or cure NAFLD/NASH, but above all substantially reduce CVD morbidity and mortality. Administration of potent statins appears safe and effective in saving lives in NAFLD/NASH patients.
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