The Associations between Kidney Function and Sexual Dysfunction among Males and Females with Type 2 Diabetes Mellitus.

Background and Objectives: Diabetic kidney disease (DKD), expressed either as albuminuria, low estimated glomerular filtration rate (eGFR) or both, and sexual dysfunction (SD), are common complications among type 2 diabetes mellitus (T2DM) patients. This study aims to assess whether an association exists between DKD and SD, erectile dysfunction (ED) or female sexual dysfunction (FSD) in a T2DM population. Materials and Methods: A cross-sectional study was designed and conducted among T2DM patients. The presence of SD was assessed using the International Index of Erectile Function and the Female Sexual Function Index questionnaires for males and females, respectively, and patients were evaluated for DKD. Results: Overall, 80 patients, 50 males and 30 females, agreed to participate. Sexual dysfunction was present in 80% of the study population. Among the participants, 45% had DKD, 38.5% had albuminuria and/or proteinuria and 24.1% had an eGFR below 60 mL/min/1.73 m2. The eGFR was associated with SD, ED and FSD. Moreover, SD and ED were proven as significant determinants for lower eGFR values in multiple linear regression analyses. DKD was associated with lower lubrication scores and eGFR was associated with lower desire, arousal, lubrication and total scores; however, the multivariate linear regression analyses showed no significant associations between them. Older age resulted in significantly lower arousal, lubrication, orgasm and total FSFI scores. Conclusions: SD is commonly encountered in older T2DM patients and DKD affects almost half of them. The eGFR has been significantly associated with SD, ED and FSD, while SD and ED were proven to be significant determinants for the eGFR levels.

Effect of sodium-glucose co-transporter-2 inhibitors on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). METHODS: We searched PubMed, Cochrane Library, and grey literature from inception to 7th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. RESULTS: We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. CONCLUSION: SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.

Effect of Empagliflozin and Dapagliflozin on Ambulatory Arterial Stiffness in Patients with Type 2 Diabetes Mellitus and Cardiovascular Co-Morbidities: A Prospective, Observational Study.

Background and Objectives: Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease. Arterial stiffness is an independent prognostic marker for cardiovascular disease development. We aimed at determining the effect of two different sodium-glucose co-transporter-2 (SGLT-2) inhibitors on ambulatory arterial stiffness in individuals with T2DM. Materials and Methods: In this single-center, single-arm, prospective study performed from January 2020 to August 2021, we planned to enroll adult subjects with T2DM and stable antidiabetic and antihypertensive treatment, assigned either to empagliflozin or dapagliflozin for 6 months. All eligible subjects underwent ambulatory blood pressure monitoring. We set as the primary efficacy outcome the change in ambulatory pulse wave velocity (PWV) from baseline to week 24. Results: We finally enrolled 46 diabetic subjects, with a mean age of 62.89 (8.53) years and mean T2DM duration of 9.72 (6.37) years. Thirty patients received dapagliflozin, while sixteen patients received empagliflozin. Due to COVID-19 pandemic restrictive measures during the study, the mean follow-up period extended from 6 months to 9.98 (3.27) months. Regarding the prespecified primary efficacy outcome, we found that the SGLT-2 inhibitor treatment did not have a significant effect on PWV (p = 0.65). Prior history of cardiovascular disease did not significantly affect the observed effects. Other indices of arterial stiffness, such as augmentation index and central pulse pressure, were not significantly affected, neither by empagliflozin nor by dapagliflozin. Conclusions: SGLT-2 inhibitor treatment with empagliflozin or dapagliflozin in subjects with T2DM failed to improve ambulatory PWV over a mean follow-up of 10 months. Registration number: ISRCTN88851713.

The presence of diabetes mellitus further impairs structural and functional capillary density in patients with chronic kidney disease.

OBJECTIVE: Endothelial dysfunction has been associated with increased cardiovascular events and overall mortality. Microvascular damage is prevalent both in diabetes mellitus (DM) and chronic kidney disease (CKD). Our aim was to compare microcirculatory function parameters in diabetic and non-diabetic CKD patients via nailfold video-capillaroscopy. METHODS: We included 48 diabetic and 48 non-diabetic adult CKD patients. All participants underwent nailfold video-capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4-minute arterial occlusion (postocclusive reactive hyperemia), and at the end of a 2-minute venous occlusion (congestion phase). RESULTS: Diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3 ± 3.8 vs 38.3 ± 4.3 capillaries/mm2 , P = .022) and at venous congestion (37.8 ± 4.0 vs 39.8 ± 4.2 capillaries/mm2 , P = .015). When stratified according to CKD stages, only in stage 3b capillary density was significantly lower in diabetic compared to non-diabetic subjects at baseline, during postocclusive hyperemia (36.8 ± 2.7 vs 40.0 ± 4.3 capillaries/mm2 , P = .037) and venous congestion (38.3 ± 2.8 vs 41.5 ± 3.5 capillaries/mm2 , P = .022). CONCLUSIONS: Capillary density during postocclusive hyperemia and after venous congestion is lower in diabetic compared to non-diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory structural and functional impairment in CKD. These differences are more prominent in CKD stage 3b.

Subclinical atherosclerosis in systemic sclerosis and rheumatoid arthritis: a comparative matched-cohort study.

Systemic autoimmune inflammatory disorders confer a higher risk of cardiovascular (CV) disease leading to increased morbidity and mortality and reduced life expectancy compared to the general population. CV risk in systemic sclerosis (SSc) has not been studied extensively but surrogate markers of atherosclerosis namely carotid intima media thickness (cIMT) and pulse wave velocity (PWV) are impaired in some but not all studies in SSc patients. The aim of this study was to investigate the prevalence of subclinical atherosclerosis assessed by cIMT and PWV between two well-characterized SSc and Rheumatoid Arthritis (RA) cohorts. Consecutive SSc patients attending the Scleroderma Clinic were compared with RA patients recruited in the Dudley Rheumatoid Arthritis Co-morbidity Cohort (DRACCO), a prospective study examining CV burden in RA. Augmentation Index (Aix75) and cIMT were measured in all participants. Propensity score matching was utilised to select patients from the two cohorts with similar demographic characteristics, CV risk factors and inflammatory load. Unpaired analysis was performed using unpaired t test for continuous variables and χ2 test for dichotomous variables. Statistical analysis was repeated using paired t test for continuous normal variables and McNemar's test for dichotomous variables. Fifty five age- and sex-matched SSc and RA patients were included in the analysis. No difference was demonstrated between SSc and RA subjects regarding cIMT (0.66 mm vs 0.63 mm, respectively) and Aix75% measurements (33.4 vs 31.7, respectively) neither in paired (p = 0.623 for cIMT and p = 0.204 for Aix%) nor in unpaired t test analysis (p = 0.137 for cIMT and p = 0.397 for AIx%). The results of this comparative study show that subclinical atherosclerosis is comparable between SSc and RA, a systemic disease with well-defined high atherosclerotic burden. Such findings underscore the importance of CV risk management in SSc in parallel with other disease-related manifestations.

Right Ventricular Function and Sexual Function: Exploring Shadows in Male and Female Patients With Heart Failure.

INTRODUCTION: Sexual health plays an important role in heart failure (HF) patients, and the relationship between HF and sexual dysfunction is well established; however, the role of right ventricular function in sexual dysfunction has not been investigated sufficiently. AIM: To investigate the potential association between right ventricular dysfunction and sexual dysfunction in both male and female patients with HF. METHODS: Patients with a clinical diagnosis of HF were evaluated in a cross-sectional study. Patients from the whole spectrum of HF were included in the study, regardless of cause, duration, and classification of HF. Sexual function in men was evaluated with the International Index of Erectile Function and in women with the Female Sexual Functioning Index. MAIN OUTCOME MEASURES: We demonstrate that right ventricular dysfunction is associated with worse sexual function in both men and women. RESULTS: 306 consecutive patients with HF participated in the study. Right ventricular systolic dysfunction ranged from 24.2-39.1% and right ventricular diastolic dysfunction from 16.1-83.1%, depending on the echocardiographic parameter that was assessed. Right ventricular systolic dysfunction assessed by tricuspid annular plane systolic excursion (TAPSE), TAPSE/pulmonary artery systolic pressure ratio, and right ventricular basal diameter was associated with a lower International Index of Erectile Function score (P = .031, P = .009, and P < .001, respectively). Multiple linear regression analysis revealed that erectile function was independently associated only with TAPSE/pulmonary artery systolic pressure ratio and tricuspid late tricuspid diastolic flow velocity wave (ß = 32.84, P = .006; and ß = -0.47, P = .026, respectively), whereas female sexual function was independently associated only with the early tricuspid diastolic flow velocity/late tricuspid diastolic flow velocity ratio (ß= -0.47, P = .026). CLINICAL IMPLICATIONS: Our study demonstrates that right ventricular dysfunction in patients with HF reflects an impaired sexual function status. Physicians should be aware of this association and closely evaluate those patients for sexual dysfunction. STRENGTHS & LIMITATIONS: We innovatively assessed the correlation between right ventricular dysfunction and sexual function using validated questionnaires. The main limitation is the relatively small sample size. CONCLUSIONS: Our study provides some new insights into the relationship between sexual dysfunction and right ventricular systolic and diastolic dysfunction in HF patients, also suggesting potential interventions to improve sexual and right ventricular function and prognosis in this population. Koutsampasopoulos K, Vogiatzis I, Ziakas A, et al. Right Ventricular Function and Sexual Function: Exploring Shadows in Male and Female Patients With Heart Failure. J Sex Med 2019;16:1199-1211.

Increased Sclerostin, but Not Dickkopf-1 Protein, Is Associated with Elevated Pulse Wave Velocity in Hemodialysis Subjects.

BACKGROUND: Sclerostin and Dickkopf-1 (Dkk-1) proteins are inhibitors of the canonical Wnt/ß-catenin bone pathway. Pilot data suggest that sclerostin may be involved in vascular changes in chronic kidney disease (CKD), but data on the effects of Dkk-1 are scarce. This is the first study investigating simultaneously the associations of sclerostin and Dkk-1 with arterial stiffness in hemodialysis patients. METHODS: A total of 80 patients on chronic hemodialysis had carotid-femoral pulse wave velocity (PWV), central blood pressure (BP), and wave reflections evaluated with applanation tonometry (Sphygmocor) on a midweek non-dialysis day. Serum levels of sclerostin and Dkk-1 were measured with ELISA. A large set of demographic, comorbid, laboratory, and drug parameters were used in the analyses. RESULTS: Subjects with PWV >9.5 m/s (high arterial stiffness group, n = 40) were older, had higher BMI, higher prevalence of hypertension, diabetes, and coronary heart disease, and higher peripheral systolic BP, central systolic BP, C-reactive protein, and serum sclerostin (p = 0.02), but similar Dkk-1, compared to subjects with low PWV. When dichotomizing the population by sclerostin levels, those with high sclerostin had higher PWV than patients with low sclerostin levels (10.63 ± 2.71 vs. 9.77 ± 3.13, p = 0.048). Increased sclerostin (>200 pg/mL) was significantly associated with increased PWV (>9.5 m/s; HR 2.778, 95% CI 1.123-6.868 per pg/mL increase); this association remained significant after stepwise adjustment for Dkk-1, intact parathyroid hormone, and calcium × phosphate product. In contrast, no association was noted between Dkk-1 and PWV (HR 1.000, 95% CI 0.416-2.403). CONCLUSION: Serum sclerostin is associated with PWV independently of routine markers of CKD-MBD in hemodialysis patients. In contrast, Dkk-1 has no association with arterial stiffness and is not pathophysiologically involved in relevant vascular changes.

Free Cortisol Is a More Accurate Marker for Adrenal Function and Does Not Correlate with Renal Function in Cirrhosis.

BACKGROUND: The accuracy of diagnosis and clinical implications of the hepatoadrenal syndrome, as currently diagnosed using total cortisol, remain to be validated. AIM: The aim of this study was to assess adrenal function using free cortisol in stable cirrhosis and study the potential implications of any abnormalities for renal and/or cardiac function. METHODS: Sixty-one stable consecutively enrolled patients with cirrhosis underwent assessment of adrenal function using the low-dose short Synacthen test, renal function by 51Cr-EDTA glomerular filtration rate (GFR), and cardiac function by two-dimensional echocardiography. RESULTS: Eleven patients (18%) had total peak cortisol (PC) < 500 nmol/L, but no patient had free PC < 33 nmol/L indicating that diagnosis of AI using total cortisol is not confirmed using free cortisol. Free cortisol did not correlate with GFR or parameters of cardiac function. Patients with higher Child-Pugh class had progressively lower free cortisol. Patients with low GFR < 60 mL/min (N = 22) had more frequently grade II-III diastolic dysfunction (66.7% vs. 17.6%; p = 0.005) and had higher Child-Pugh and MELD score compared to those with normal GFR. CONCLUSIONS: Diagnosis of AI using total cortisol is not confirmed using free cortisol and is thus considered unreliable in cirrhosis. Free cortisol is not associated with renal or cardiac dysfunction. Lower free cortisol in more advanced stages of liver disease might be secondary to decreased synthesis due to lower cholesterol levels. Irrespective of free cortisol, parameters of cardiac dysfunction are associated with renal impairment supporting the cardio-renal hypothesis.

Stroke paradox with SGLT-2 inhibitors: a play of chance or a viscosity-mediated reality?

Diabetes mellitus is a major risk factor for cardiovascular morbidity and mortality. Current therapeutic strategies have not provided constant beneficial cardiovascular-related results. Sodium-glucose co-transporters 2 (SGLT-2) inhibitors have emerged as a novel antidiabetic class of drugs that exert favourable results in a variety of other cardiovascular risk factors too, such as increased blood pressure and body weight. The Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) study was the first trial that evaluated cardiovascular outcomes in patients with diabetes with the use of empagliflozin, a member of this new class of drugs. Empagliflozin was associated with remarkable reduction of cardiovascular morbidity and mortality and all-cause death. On the contrary, stroke incidence was slightly increased, although the result did not reach statistical significance. It could be assumed that a drug providing such beneficial effects on cardiovascular outcomes, would have also the same impact in stroke risk. This finding could theoretically be attributed to 'play of chance'. However, an increase of haematocrit was observed in EMPA-REG and other SGLT-2 inhibitors studies. Accumulating evidence suggests a direct association between increased haematocrit and stroke risk. Could this 'stroke paradox' be a result of the increased haematocrit levels noted with SGLT-2 inhibitors? The aim of this review is to critically assess both possibilities, given that increased stroke rates (if indeed true) should not be neglected and unattended.

Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection.

AIM: No randomized study has been conducted to investigate the use of intravenous paracetamol (acetaminophen, APAP) for the management of fever due to infection. The present study evaluated a new ready-made infusion of paracetamol. METHODS: Eighty patients with a body temperature onset ≥38.5°C in the previous 24 h due to infection were randomized to a single administration of placebo (n = 39) or 1 g paracetamol (n = 41), and their temperature was recorded at standard intervals. Rescue medication with 1 g paracetamol was allowed. Serum samples were collected for the measurement of APAP and its metabolites. The primary endpoint was defervescence, defined as a core temperature ≤37.1°C. RESULTS: During the first 6 h, defervescence was achieved in 15 (38.5%) patients treated with placebo compared with 33 (80.5%) patients treated with paracetamol 1 g (P < 0.0001). The median time to defervescence with paracetamol 1 g was 3 h. Rescue medication was given to 15 (38.5%) and five (12.2%) patients allocated to placebo and paracetamol, respectively (P = 0.007); nine (60.0%) and two (40.0%) of these patients, respectively, experienced defervescence. No further antipyretic medication was needed for patients becoming afebrile with rescue medication. Serum glucuronide-APAP concentrations were significantly greater in the serum of patients who did not experience defervescence with paracetamol. The efficacy of paracetamol was not affected by serum creatinine. No drug-related adverse events were reported. CONCLUSIONS: The 1 g paracetamol formulation has a rapid and sustainable antipyretic effect on fever due to infection. Its efficacy is dependent on hepatic metabolism.

Should we expand the concept of coronary heart disease equivalents?

PURPOSE OF REVIEW: This narrative review discusses the associations between metabolic and inflammatory diseases, as well as radiotherapy and chemotherapy with coronary heart disease (CHD) and related risk factors, to support (or not) their potential role as CHD equivalents. RECENT FINDINGS: Although not regarded as CHD equivalents, several metabolic and inflammatory disorders are associated with an increased risk of CHD morbidity and/or mortality. These conditions include metabolic syndrome, impaired glucose metabolism, nonalcoholic fatty liver disease, obstructive sleep apnoea syndrome, erectile dysfunction, periodontitis, inflammatory bowel diseases, systemic vasculitis and HIV infection, as well as chemotherapy and radiotherapy. SUMMARY: More research should be carried out to identify which conditions can be added to the list of CHD equivalents.

The effect of continuous positive airway pressure therapy on blood pressure and arterial stiffness in hypertensive patients with obstructive sleep apnea.

AIM: We aimed to evaluate the effect of continuous positive airway pressure (CPAP) therapy on blood pressure (BP) and arterial stiffness in hypertensive patients with obstructive sleep apnea (OSA). PATIENTS AND METHODS: We studied 38 hypertensive patients who suffered from severe OSA. Ambulatory BP measurement was performed at baseline and after at least 3 months of uninterrupted CPAP therapy. In 19 of these patients, we also measured pulse wave velocity (PWV) at baseline, after the first night of CPAP therapy and at 3 months. Fifteen normotensive subjects without OSA comprised the control group. RESULTS: CPAP therapy reduced systolic BP from 141.5 ± 12.1 to 133.5 ± 9.7 mmHg (p = 0.007) and diastolic BP from 87.8 ± 6.8 to 83 ± 5.4 mmHg (p = 0.004). CPAP also reduced the PWV from 8.81 ± 1.4 to 8.18 ± 1 m/s after the first night of CPAP therapy (p = 0.003) and to 7.37 ± 1 m/s at 3 months (p = 0.007). CONCLUSIONS: To the best of our knowledge, this is the first study demonstrating that CPAP therapy in hypertensive patients with OSA improves arterial stiffness from the first night and that this favorable effect is maintained for at least 3 months of CPAP use. A reduction in BP was also observed, even though BP control was not always achieved.

Efficacy of various "classic" echocardiographic and laboratory indices in distinguishing the "gray zone" between athlete's heart and hypertrophic cardiomyopathy: a pilot study.

Left ventricular hypertrophy (LVH) with intraventricular septum thickness (IVST) between 1.2 and 1.5 cm in athletes represents a "gray zone" between physiologic adaptation and mild hypertrophic cardiomyopathy (HCM). Various echo and laboratory parameters have been reported till now in the literature to discriminate the "gray zone" entities. Aim of this study was to assess the efficacy of these "classic" parameters in differentiating physiologic LVH in athletes from mild HCM in a highly selected population. Nine highly trained athletes with IVST (1.28 ± 0.07 cm), 9 patients with mild HCM (1.38 ± 0.11 cm), and 26 athletes without LVH (1.06 ± 0.09 cm; P < 0.0005) underwent echocardiographic study, cardiopulmonary treadmill exercise stress test, and brain natriuretic peptide (BNP) measurement before and after exercise. Among all parameters tested, 7 were found to significantly differ between "gray zone" groups. After bootstrapping analysis, it was found that athletes with left ventricular end-diastolic diameter <4.74 cm, mitral deceleration time >200 ms, isovolumic relaxation time >94 ms, tricuspid E/A < 1.63, septum Em < 9.5 cm/sec, relative wall thickness >0.445, and a BNP value at rest >9.84 pg/mL had a greater possibility for having underlying cardiomyopathy. A 10-point score based on these parameters showed accuracy (area under the curve = 0.958 [95%CI: 0.738-1.0; P = 0.00005, standard error = 0.0342]) for revealing HCM in a gray zone athletic population. Differentiation of adaptive LVH versus HCM in a gray zone population could be facilitated by recognition of certain features referring to LV dimensions, diastolic function, and BNP.

The role of asymmetric dimethylarginine in endothelial dysfunction and abnormal nitric oxide metabolism in systemic sclerosis: results from a pilot study.

INTRODUCTION/OBJECTIVES: Systemic sclerosis (SSc) is characterized by generalized vasculopathy affecting mainly small vessels while macrovascular involvement is less investigated. The aim of this study was to examine associations between asymmetric dimethylarginine (ADMA) - a biomarker of atherosclerosis - and assessments of macrovascular endothelial function in patients with SSc. METHODS: This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA measurement in serum samples was based on an enzyme immunoassay technique. Participants underwent blood pressure measurement according to 2018 ESC/ESH Guidelines, applanation tonometry for the evaluation of arterial stiffness, and carotid ultrasound for the measurement of the intima-media thickness (cIMT). RESULTS: Eighty-one Caucasians (82.3% female) SSc individuals with mean age 55.44 ± 13.4 years were included in this analysis. The correlation analysis of ADMA levels (unadjusted and adjusted values) with functional and morphological parameters of atherosclerosis revealed no statistically significant associations. Subgroup analysis based on disease duration (≤ 4 years), immunologic profile (SCL-70 and ACA antibodies), disease type (limited, diffuse), and inflammatory status (erythrocyte sedimentation rate [ESR] > 25 mm/h and C-reactive protein [CRP] > 5 mg/L) showed no associations, except from a significant positive correlation between ADMA levels and cΙΜΤmean (r = 0.370, p = 0.044) in individuals with early SSc. CONCLUSIONS: The results of the study suggest that ADMA may be related with accelerated atherosclerosis in early stages of the disease. However, the lack of association between other morphological and functional parameters of endothelial dysfunction may suggest that other regulators of nitric oxide metabolism may contribute to macrovascular injury in SSc in various phases of the disease. Key Points • ADMA is a biomarker of atherosclerosis and has been linked with microvascular complications of SSc. •ADMA was not correlated with morphological and functional parameters of atherosclerosis in the population of the study. •The demonstrated association between ADMA and cIMT in patients with early SSc may suggest a role of NO/ADMA pathway in the initiation of macrovascular injury in SSc.

Cardiovascular Outcomes with Finerenone According to Glycemic Status at Baseline and Prior Treatment with Newer Antidiabetics among Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) and cardiovascular disease are closely interconnected. We sought to determine the cardioprotective action of finerenone according to prior treatment with newer antidiabetics and glycemic status. We searched PubMed and Cochrane Library from inception to October 1, 2021 for randomized controlled trials (RCTs) assessing the effect of finerenone on major adverse cardiovascular outcomes in patients with T2DM. We set the primary endpoint as major adverse cardiovascular events (MACE), defined as the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. We finally included two RCTs in our quantitative synthesis. Compared to placebo, finerenone induced a 23% risk reduction for the composite cardiovascular endpoint, regardless of prior glycemia. We also showed that finerenone provided significant cardiovascular benefit for obese patients with T2DM compared to placebo, although this benefit was diminished for subjects with a body mass index lower than 30 kg/m2. Finally, the combination of finerenone with sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists did not produce a significant risk reduction for MACE. We conclude that finerenone provides significant cardiovascular benefits for patients with T2DM, especially for those who are obese, while glycemic status or treatment with newer antidiabetics at baseline does not affect the observed cardioprotective action.

Arterial Stiffness as a Cardiovascular Risk Factor for the Development of Preeclampsia and Pharmacopreventive Options.

Arterial Stiffness (AS) describes the rigidity of the arterial walls. Epidemiological studies have shown that increased AS is an independent predictive marker of Cardiovascular (CV) morbidity and mortality in both pregnant and non-pregnant women. Preeclampsia (PE), a form of pregnancy-induced hypertension, affects approximately 5% of pregnancies worldwide. Preeclamptic women have a higher risk of CV Disease (CVD), mainly because PE damages the heart's ability to relax between contractions. Different pharmacological approaches for the prevention of PE have been tested in clinical trials (e.g., aspirin, enoxaparin, metformin, pravastatin, and sildenafil citrate). In current clinical practice, only low-dose aspirin is used for PE pharmacoprevention. However, low-dose aspirin does not prevent term PE, which is the most common form of PE. Compromised vascular integrity precedes the onset of PE and therefore, AS assessment may constitute a promising predictive marker of PE. Several non-invasive techniques have been developed to assess AS. Compared with normotensive pregnancies, both Carotid-Femoral Pulse Wave Velocity (cfPWV) and Augmentation Index (AIx) are increased in PE. In view of simplicity, reliability, and reproducibility, there is an interest in oscillometric AS measurements in pregnancies complicated by PE.

Serum adipokine levels in patients with type 1 diabetes are associated with degree of obesity but only resistin is independently associated with atherosclerosis markers.

PURPOSE: The role of adipokines in causing inflammation and insulin resistance in normal weight and obese patients is generally well studied. However, there are often conflicting results regarding their levels in type 1 diabetes mellitus (T1DM) patients and their relationship to micro- and macrovascular disease. We therefore investigated which serum adipokine levels are independently associated with markers of early atherosclerosis and microvascular complications in patients with T1DM. METHODS: A cross-sectional study was performed in the Diabetes Outpatient Clinic of Hippokrateion General Hospital, Thessaloniki, Greece. Sixty T1DM patients (30 females, mean age 38.8 ± 10.6 years, mean diabetes duration 17.4 ± 9.9 years) were included. Plasma adiponectin, leptin, and resistin, carotid artery intima media thickness (cIMT), and arterial stiffness (pulse wave velocity, PWV/SpygmoCor CP System and Mobil-O-Graph 24 h PWA) were assessed. RESULTS: Leptin and resistin levels were significantly higher in overweight and obese patients (p = 0.002 and p = 0.039, respectively). Adiponectin was the only adipokine negatively correlated with BMI (rs = - 0.41, p = 0.001). We report a bivariate association between serum adiponectin levels and retinopathy (p = 0.007). Resistin was the only adipokine that showed significant correlation with systolic (rs = 0.42, p = 0.001) and diastolic (rs = 0.29, p = 0.024) hypertension and PWV (p = 0.035). CONCLUSIONS: Serum adipokine levels demonstrate similar bivariate associations with anthropometric variables in patients with T1DM to those in normal weight subjects. Although microvascular complications are associated with serum adipokine levels by bivariate analysis, only resistin, an inflammatory marker, is independently associated with arterial stiffness in patients with T1DM.

Right ventricular performance in patients with heart failure with mildly reduced ejection fraction: the forgotten ventricle.

Right ventricular (RV) function is a major determinant of prognosis and adverse outcomes in patients with heart failure (HF). It is largely unknown if HF with mildly reduced ejection fraction (HFmrEF) patients have some special characteristics in RV function (RVF) that may distinguish them from HF with reduced or preserved ejection fraction (HFrEF or HFpEF) patients. Standard echocardiography was performed to estimate RVF [tricuspid annular systolic velocity (TDSV), plane systolic excursion (TAPSE), TAPSE to pulmonary artery systolic pressure (TAPSE/PASP) and RV myocardial performance index (MPI-TEI index)] in a cross-sectional study. In 306 participants, the RV systolic function evaluated with TAPSE and TDSV was impaired in 39.1 and 24.2%, respectively. TAPSE, TAPSE/PASP and TDSV were lower in HFmrEF compared with HFpEF and higher compared with HFrEF (p < 0.001 for among-groups comparison). RV diastolic dysfunction varied between 12.6 and 43.8% depending on the echocardiographic parameter. Diastolic RVF determined by tricuspid inflow E/A wave ratio (Et/At) was impaired in less patients with HFmrEF compared with those with HFpEF or HFrEF (25.9% vs 48.4% vs 56.3%; p = 0.030, respectively). RV diastolic dysfunction by et'/at' (tissue Doppler tricuspid valve annulus e' and a' waves) was impaired in less patients with HFmrEF compared with HFrEF (11.8% vs 33.3%; p = 0.019). A multivariate regression analysis revealed a significant association between RV and LV systolic dysfunction. The present study shows a high prevalence of RV dysfunction in HFmrEF patients. Study findings provides some new insights on RV and LV systolic dysfunction coupling whereas RV diastolic dysfunction was not dependent on LV systolic dysfunction.