Mechanisms of Vascular Inflammation and Potential Therapeutic Targets: A Position Paper From the ESH Working Group on Small Arteries.

Inflammatory responses in small vessels play an important role in the development of cardiovascular diseases, including hypertension, stroke, and small vessel disease. This involves various complex molecular processes including oxidative stress, inflammasome activation, immune-mediated responses, and protein misfolding, which together contribute to microvascular damage. In addition, epigenetic factors, including DNA methylation, histone modifications, and microRNAs influence vascular inflammation and injury. These phenomena may be acquired during the aging process or due to environmental factors. Activation of proinflammatory signaling pathways and molecular events induce low-grade and chronic inflammation with consequent cardiovascular damage. Identifying mechanism-specific targets might provide opportunities in the development of novel therapeutic approaches. Monoclonal antibodies targeting inflammatory cytokines and epigenetic drugs, show promise in reducing microvascular inflammation and associated cardiovascular diseases. In this article, we provide a comprehensive discussion of the complex mechanisms underlying microvascular inflammation and offer insights into innovative therapeutic strategies that may ameliorate vascular injury in cardiovascular disease.

The Impact of Metabolic Syndrome Components on Erectile Function in Patients with Type 2 Diabetes.

Erectile dysfunction is commonly encountered in diabetic patients and in patients with metabolic syndrome; however, only a few studies have assessed patients with metabolic syndrome and type 2 diabetes mellitus (T2DM) regarding their sexual function. The purpose of this study is to examine the effect of metabolic syndrome and its components on the erectile function of T2DM patients. A cross-sectional study including T2DM patients was conducted from November 2018 until November 2020. Participants were evaluated for the presence of metabolic syndrome and their sexual function was assessed using the International Index of Erectile Function (IIEF) questionnaire. A total of 45 consecutive male patients participated in this study. Metabolic syndrome was diagnosed in 84.4% and erectile dysfunction (ED) in 86.7% of them. Metabolic syndrome was not associated with ED or ED severity. Among metabolic syndrome components, only high-density lipoprotein cholesterol (HDL) was associated with ED [x2 (1, n = 45) = 3.894, p = 0.048; OR = 5.5 (95% CI: 0.890-33.99)] and with the IIEF erectile function scores (median 23 vs. 18, U = 75, p = 0.012). Multiple regression analyses showed that HDL was non-significantly associated with the IIEF erectile function scores. In conclusion, among T2DM patients HDL is associated with ED.

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.

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.

Impact of Primary Aldosteronism in Resistant Hypertension.

PURPOSE OF REVIEW: In this narrative review, we aim to summarize the latest data on the association between primary aldosteronism and resistant hypertension, as well as to emphasize the necessity for screening for primary aldosteronism all patients with resistant hypertension. RECENT FINDINGS: Epidemiological data suggests that up to one out of five patients with resistant hypertension suffer from primary aldosteronism. Patients with primary aldosteronism have increased incidence of renal disease, diabetes mellitus, atrial fibrillation, and obstructive sleep apnea, as well as they are characterized by an extended target organ damage and increased cardiovascular morbidity and mortality. Specific treatments for primary hyperaldosteronism (adrenalectomy and mineralocorticoid receptor antagonists) have significant impact on blood pressure, can reverse target organ damage, and mitigate cardiovascular risk. All patients with resistant hypertension should be evaluated for primary aldosteronism. Patients diagnosed with the disease may further undergo lateralization with adrenal vein sampling in order to receive the optimal therapeutic option which results in significant improvements in quality of life and cardiovascular profile.

Assessment of skin microcirculation in primary aldosteronism: impaired microvascular responses compared to essential hypertensives and normotensives.

Primary aldosteronism (PA) is associated with considerably higher cardiovascular risk and increased prevalence of organ damage compared to essential hypertension (EH). Laser speckle contrast imaging (LSCI) has emerged as a novel non-invasive tool to assess of skin microcirculation. Our aim was to evaluate skin microvascular function (SMF) using LSCI coupled with post-occlusive reactive hyperemia (PORH) in a group of PA patients (PAs) compared to patients with EH (EHs) and normotensive controls (NTs). We enrolled PAs, age- and gender-matched with EHs and NTs. All participants underwent SMF assessment by LSCI with PORH. We enrolled 109 participants including 29 PAs, 47 EHs, and 33 NTs. SMF was significantly impaired in PAs, including peak time (p < 0.001) and base to peak flux (p < 0.001) compared to NTs and EHs. Among PAs, plasma aldosterone showed a positive correlation with occlusion flux (p = 0.005). Our study shows for the first time that PAs present impaired SMF as assessed with LSCI coupled with PORH, not only compared to NTs but also compared to EHs with similar blood pressure profile. Further studies are needed to investigate the clinical impact of such alterations in terms of pathophysiology and cardiovascular risk prediction.

Hypertension in Pregnancy: Unanswered Questions.

BACKGROUND: Hypertension of pregnancy [office blood pressure (BP) levels≥140/90 mmHg] is fairly common and can affect up to 10% of pregnant women worldwide. Hypertension of pregnancy is an important risk factor for the mother and carries increased morbidity and mortality for the fetus. Women with hypertension of pregnancy have a high-risk for future cardiovascular and renal events. OBJECTIVES: To summarize the literature related to several clinical aspects of hypertension in pregnancy and draw clinically meaningful conclusions. METHODS: We conducted an in-depth review of the literature to retrieve existing data on the definition, epidemiology, classification, and management of hypertension in pregnancy. RESULTS: All pregnant women with hypertension should have a proper diagnostic workup and be treated appropriately. In women with mild hypertension, BP therapeutic target should be set to 110-140/80-85mmHg. In women with severe hypertension, BP should be reduced by at least 25% as soon as possible, and gradually thereafter to normal target levels of <140/105mmHg. In terms of preeclampsia, physicians need to consider potential complications and formulate prevention strategies. The choice of antihypertensive medication is crucial since certain classes can be detrimental to the fetus and should be avoided. Post-partum, the choice of antihypertensive therapy of the mother should take into consideration breastfeeding of the fetus. Given the life-long cardiovascular risk of women with pregnancy hypertension, a regular cardiovascular evaluation is in order. CONCLUSION: Albeit the antihypertensive treatment exerts significant benefits for both the mother and the baby, several clinical aspects remain un-tackled. More research is needed to further improve the treatment of such disorders.

The effect of glucagon-like peptide-1 receptor agonists on 24-hour ambulatory blood pressure: a confirmatory meta-analysis.

OBJECTIVE: Hypertension augments overall cardiovascular risk in patients with type 2 diabetes mellitus (T2DM); however, control rates remain suboptimal. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have revolutionized the field of T2DM therapeutic management due to their multiple pleiotropic effects. Therefore, we sought to determine the effect of this class on ambulatory blood pressure monitoring (ABPM), pooling data from relevant randomized controlled trials (RCTs). METHODS: We searched major electronic databases, namely PubMed and Cochrane Library, along with gray literature sources, for RCTs assessing the effect of various GLP-1RAs on ambulatory BP in patients with T2DM. RESULTS: We pooled data from seven RCTs in total. GLP-1RA treatment compared to placebo or active control resulted in a nonsignificant decrease in 24-h SBP (mean difference = -1.57 mm Hg; 95% CI,-4.12 to 0.98; I2 = 63%) and in 24-h DBP (mean difference = 1.28 mmHg; 95% CI,-0.31 to 2.87; I2 = 49%). No subgroup differences between the various GLP-1RAs were detected. CONCLUSION: GLP-1RAs treatment does not influence either systolic or diastolic ambulatory BP in patients with T2DM.

Inflammatory Markers in Cardiovascular Disease; Lessons Learned and Future Perspectives.

BACKGROUND: Cardiovascular disease (CVD) still remains the leading cause of morbidity and mortality worldwide. It is now established that inflammation plays a crucial role in atherosclerosis and atherothrombosis, and thus, it is closely linked to cardiovascular disease. OBJECTIVE: The aim of the present review is to summarize and critically appraise the most relevant evidence regarding the potential use of inflammatory markers in the field of CVD. METHODS: We conducted a comprehensive research of the relevant literature, searching MEDLINE from its inception until November 2018, primarily for meta-analyses, randomized controlled trials and observational studies. RESULTS: Established markers of inflammation, mainly C-reactive protein, have yielded significant results both for primary and secondary prevention of CVD. Newer markers, such as lipoprotein-associated phospholipase A2, lectin-like oxidized low-density lipoprotein receptor-1, cytokines, myeloperoxidase, cell adhesion molecules, matrix metalloproteinases, and the CD40/CD40 ligand system, have been largely evaluated in human studies, enrolling both individuals from the general population and patients with established CVD. Some markers have yielded conflicting results; however, others are now recognized not only as promising biomarkers of CVD, but also as potential therapeutic targets, establishing the role of anti-inflammatory and pleiotropic drugs in CVD. CONCLUSION: There is significant evidence regarding the role of consolidated and novel inflammatory markers in the field of diagnosis and prognosis of CVD. However, multimarker model assessment, validation of cut-off values and cost-effectiveness analyses are required in order for those markers to be integrated into daily clinical practice.

The Impact of Various Blood Pressure Measurements on Cardiovascular Outcomes.

Hypertension is a potent risk factor for cardiovascular morbidity and mortality. High blood pressure (BP) correlates closely with all-cause and cardiovascular mortality. Although the gold standard remains office BP (auscultatory or automated), other methods (central or out-of-office) are gaining popularity as better predictors of CV events. In this review, we investigated the prognostic value of each method of BP measurement and explored their advantages and pitfalls. Unattended automated office BP is a novel technique of BP measurement with promising data. Ambulatory BP monitoring, and to a lesser extent, home BP measurements, seem to predict cardiovascular events and mortality outcomes better, while at the same time, they can help distinguish hypertensive phenotypes. Data on the association of central BP levels with cardiovascular and mortality outcomes, are conflicting. Future extensive cross-sectional and longitudinal studies are needed to evaluate head-to-head the corresponding levels and results of each method of BP measurement, as well as to highlight disparities in their prognostic utility.