Sexual function scores are associated with arterial stiffness in postmenopausal women.

BACKGROUND: Female sexual dysfunction (FSD) has been suggested to be correlated with the burden of cardiovascular risk factors. AIM: We aimed to evaluate the possible association between functional indices of vascular function and FSD scores in apparently healthy postmenopausal women. METHODS: This cross-sectional study included 116 postmenopausal women who underwent assessment of endothelial function with measurement of flow-mediated dilation (FMD) of the branchial artery and arterial stiffness estimation with measurement of the carotid-femoral pulse wave velocity (PWV). We used the Greene Climacteric Scale to evaluate vasomotor symptomatology, the Female Sexual Function Index (FSFI) to evaluate FSD and the Beck Depression Inventory to evaluate mood disorder. Low sexual function was defined as an FSFI score <26.55. OUTCOMES: These included FSFI and low sexual function scores as well as measures of PWV and FMD. RESULTS: Sexual function scores were associated with measures of blood pressure (normal vs low sexual function; systolic blood pressure: 120.2 ± 15.0 mm Hg vs 113.4 ± 14.6 mm Hg; analysis of covariance P = .026; diastolic blood pressure: 75.9 ± 10.5 mm Hg vs 70.3 ± 9.9 mm Hg; analysis of covariance P = .012; both adjusted for age, body mass index, current smoking, and PWV). Systolic blood pressure, but not diastolic blood pressure, was associated with FSFI (B = 0.249, P = .041) and PWV (B = 0.392, P < .001). PWV measures were associated with FSFI (B = -0.291, P = .047) and pulse pressure (B = 0.355, P = .017). FMD measures were also associated with FSFI (B = 0.427, P = .033). All models were adjusted for age, body mass index, current smoking, insulin resistance, vasomotor symptomatology, and Beck Depression Inventory. CLINICAL IMPLICATIONS: Our findings demonstrate that lower scores of sexual function are associated with deteriorated vascular function mainly manifested as arterial stiffening, further contributing to systolic blood pressure changes. STRENGTHS AND LIMITATIONS: The strength of this study is the carefully selected healthy sample of postmenopausal women, with simultaneous assessment of climacteric symptomatology and mood disorders. The limitations include the small sample size, the cross-sectional design, and the recruitment of consecutive outpatients of a university menopause clinic. CONCLUSION: Longitudinal studies and interventions to improve FSD should further assess the clinical relevance of these findings.

Transthyretin Amyloidosis Cardiomyopathy in Greece: Clinical Insights from the National Referral Center.

BACKGROUND: Clinical characteristics and outcomes of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) vary by region, necessitating the acquisition of country-specific evidence for proper management. METHODS: This is an observational study including sequential patients presenting in the Amyloidosis Reference Center of Greece, from 01/2014 to 12/2022. ATTR-CM was diagnosed by positive scintigraphy and exclusion of light-chain amyloidosis or positive biopsy typing. Genetic testing was performed in all cases. RESULTS: One-hundred and nine ATTR-CM patients were included (median age, 81 years) of which 15 carried TTR mutations (27% Val30Met). Most patients (82%) presented with heart failure and 59% with atrial fibrillation, while 10% had aortic stenosis. Importantly, 78 (71.6%) had clinically significant extracardiac manifestations (45% musculoskeletal disorder, 40% peripheral neuropathy and 33% gastrointestinal symptoms). Sixty-five (60%) received disease-specific treatment with tafamidis. Estimated median survival was 48 months; advanced NYHA class, National Amyloidosis Center stage, eGFR<45 ml/kg/1.73m2, NT-pro-BNP>5000 pg/mL were associated with worse survival, while tafamidis treatment was associated with improved survival in patients with IVS≥ 12 mm. DISCUSSION: These are the first data describing the characteristics, management, and outcomes of patients with ATTR-CM in Greece, which could influence local guidelines. SHORT TITLE: Transthyretin cardiomyopathy in Greece.

Cathepsin S Levels and Survival Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are at high residual risk for long-term cardiovascular (CV) mortality. Cathepsin S (CTSS) is a lysosomal cysteine protease with elastolytic and collagenolytic activity that has been involved in atherosclerotic plaque rupture. OBJECTIVES: The purpose of this study was to determine the following: 1) the prognostic value of circulating CTSS measured at patient admission for long-term mortality in NSTE-ACS; and 2) its additive value over the GRACE (Global Registry of Acute Coronary Events) risk score. METHODS: This was a single-center cohort study, consecutively recruiting patients with adjudicated NSTE-ACS (n = 1,112) from the emergency department of an academic hospital. CTSS was measured in serum using enzyme-linked immunosorbent assay. All-cause mortality at 8 years was the primary endpoint. CV death was the secondary endpoint. RESULTS: In total, 367 (33.0%) deaths were recorded. CTSS was associated with increased risk of all-cause mortality (HR for highest vs lowest quarter of CTSS: 1.89; 95% CI: 1.34-2.66; P < 0.001) and CV death (HR: 2.58; 95% CI: 1.15-5.77; P = 0.021) after adjusting for traditional CV risk factors, high-sensitivity C-reactive protein, left ventricular ejection fraction, high-sensitivity troponin-T, revascularization and index diagnosis (unstable angina/ non-ST-segment elevation myocardial infarction). When CTSS was added to the GRACE score, it conferred significant discrimination and reclassification value for all-cause mortality (Delta Harrell's C: 0.03; 95% CI: 0.012-0.047; P = 0.001; and net reclassification improvement = 0.202; P = 0.003) and CV death (AUC: 0.056; 95% CI: 0.017-0.095; P = 0.005; and net reclassification improvement = 0.390; P = 0.001) even after additionally considering high-sensitivity troponin-T and left ventricular ejection fraction. CONCLUSIONS: Circulating CTSS is a predictor of long-term mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score.

Determining patterns of vascular function and structure in wild-type transthyretin cardiac amyloidosis. A comparative study.

BACKGROUND: The impact of wild-type transthyretin-related cardiac amyloidosis (ATTRwt) on functional and structural peripheral vascular measures is unknown. In the present study, we explored patterns of vascular dysfunction in patients with ATTRwt in comparison to diseases with similar cardiac phenotype. METHODS: Treatment-naïve patients with ATTRwt (n = 32) were compared to: 1. Age-and sex-matched reference population without amyloidosis (n = 32), 2. Age-and sex-matched patients with systemic AL amyloidosis (n = 32), and 3. patients with cardiac AL amyloidosis (AL-HF, n = 23) or elderly patients with heart failure with preserved ejection fraction (HFpEF) (n = 16). All subjects underwent peripheral vascular assessment using carotid artery ultrasonography, brachial artery flow-mediated dilation (FMD), measurement of arterial stiffness and aortic hemodynamics including heart rate-adjusted time of return of reflected waves (Tr/HR). RESULTS: After adjustment for traditional cardiovascular risk factors and coronary artery disease (core model), peripheral and aortic blood pressures (BP) were lower in patients with ATTRwt (p < 0.05) whereas other vascular markers were preserved compared to the reference non-amyloidosis group. ATTRwt was independently associated with lower BP and longer Tr/HR compared to AL. Compared to AL-HF, FMD was lower in ATTRwt (p = 0.033). ATTRwt patients had lower BP and higher Tr/HR than HFpEF (p < 0.05). By ROC analysis, Tr/HR discriminated ATTRwt vs. AL-HF (sensitivity 93%, specificity 75%) and HFpEF (sensitivity 100%, specificity 94%) and lower FMD increased the likelihood for ATTRwt at low Tr/HR values. CONCLUSION: ATTRwt patients present a distinct peripheral vascular fingerprint which is different from AL-HF or HFpEF, consisting of lower peripheral and aortic BP, prolonged Tr/HR and FMD at reference-population range.

COVID-19 and myocarditis: a systematic review and overview of current challenges.

Myocardial inflammation in COVID-19 has been documented. Its pathogenesis is not fully elucidated, but the two main theories foresee a direct role of ACE2 receptor and a hyperimmune response, which may also lead to isolated presentation of COVID-19-mediated myocarditis. The frequency and prognostic impact of COVID-19-mediated myocarditis is unknown. This review aims to summarise current evidence on this topic. We performed a systematic review of MEDLINE and Cochrane Library (1/12/19-30/09/20). We also searched clinicaltrials.gov for unpublished studies testing therapies with potential implication for COVID-19-mediated cardiovascular complication. Eligible studies had laboratory confirmed COVID-19 and a clinical and/or histological diagnosis of myocarditis by ESC or WHO/ISFC criteria. Reports of 38 cases were included (26 male patients, 24 aged < 50 years). The first histologically proven case was a virus-negative lymphocytic myocarditis; however, biopsy evidence of myocarditis secondary to SARS-CoV-2 cardiotropism has been recently demonstrated. Histological data was found in 12 cases (8 EMB and 4 autopsies) and CMR was the main imaging modality to confirm a diagnosis of myocarditis (25 patients). There was a substantial variability in biventricular systolic function during the acute episode and in therapeutic regimen used. Five patients died in hospital. Cause-effect relationship between SARS-CoV-2 infection and myocarditis is difficult to demonstrate. However, current evidence demonstrates myocardial inflammation with or without direct cardiomyocyte damage, suggesting different pathophysiology mechanisms responsible of COVID-mediated myocarditis. Established clinical approaches should be pursued until future evidence support different actions. Large multicentre registries are advisable to elucidate further.

Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease.

Long non-coding RNAs (lncRNAs) have emerged as critical regulators in human disease including atherosclerosis. However, the mechanisms involved in the post-transcriptional regulation of the expression of disease-associated lncRNAs are not fully understood. Gene expression studies revealed that Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) lncRNA expression was increased by >2-fold in peripheral blood mononuclear cells (PBMCs) derived from patients with coronary artery disease (CAD) or in carotid artery atherosclerotic plaques. We observed a linear association between NEAT1 lncRNA expression and prevalence of CAD which was independent of age, sex, cardiovascular traditional risk factors and renal function. NEAT1 expression was induced by TNF-α, while silencing of NEAT1 profoundly attenuated the TNF-α-induced vascular endothelial cell pro-inflammatory response as defined by the expression of CXCL8, CCL2, VCAM1 and ICAM1. Overexpression of the RNA editing enzyme adenosine deaminase acting on RNA-1 (ADAR1), but not of its editing-deficient mutant, upregulated NEAT1 levels. Conversely, silencing of ADAR1 suppressed the basal levels and the TNF-α-induced increase of NEAT1. NEAT1 lncRNA expression was strongly associated with ADAR1 in CAD and peripheral arterial vascular disease. RNA editing mapping studies revealed the presence of several inosines in close proximity to AU-rich elements within the AluSx3+/AluJo- double-stranded RNA complex. Silencing of the stabilizing RNA-binding protein AUF1 reduced NEAT1 levels while silencing of ADAR1 profoundly affected the binding capacity of AUF1 to NEAT1. Together, our findings propose a mechanism by which ADAR1-catalyzed A-to-I RNA editing controls NEAT1 lncRNA stability in ASCVD.

A Bayesian meta-analysis on early tobacco exposure and vascular health: From childhood to early adulthood.

BACKGROUND: Smoking has been consistently associated with increased cardiovascular risk in adults. Although exposure to tobacco products often starts in early life, evidence for the possible adverse effects on the cardiovascular system of the young is scarce. We sought to derive pooled estimates of smoking effects on indices of early vascular damage in children and adolescents. DESIGN AND METHODS: We performed a systematic review and meta-analysis of clinical studies involving young individuals up to 21 years old that provided data on smoking exposure (active or passive) and flow-mediated dilatation, carotid to femoral pulse wave velocity and maximum carotid intima-media thickness. We employed three distinct methodologies of random-effects data synthesis, including the Sidik-Jonkman estimator, the Hartung and Knapp correction and a Bayesian method with a well-informed prior on the level of between-study variance. RESULTS: In 12 studies and 5279 individuals in total, smoking exposure was related to deterioration in all three outcomes (mean adjusted flow-mediated dilatation decrease: -0.77%, 95% confidence interval -1.38--0.15, mean adjusted pulse wave velocity increase: 0.1 m/s, 95% confidence interval 0.02-0.17 and mean adjusted carotid intima-media thickness increase: 0.35 mm, 95% confidence interval 0.16-0.55, for the Sidik-Jonkman estimator). No difference was established between active and passive smoking on associations with arterial damage. CONCLUSIONS: Exposure to tobacco products is associated with subclinical vascular damage early in life, even from childhood. Public health initiatives should target these very young age groups to prevent early smoking exposure and associated arterial damage and its sequelae.