Erectile dysfunction in cardiovascular patients: A prospective study of the eNOS gene T-786C, G894T, and INTRON variable number of the tandem repeat functional interaction.

BACKGROUND: Cardiovascular disease induces erectile dysfunction modulated by endothelial nitric oxide synthase enzyme and an impaired ejection fraction that restricts penis vascular congestion. However, the mechanisms regulating endothelial dysfunction are not understood. OBJECTIVES: Exploring the functional impact of endothelial nitric oxide synthase genetic polymorphisms on erectile dysfunction and drug therapy optimization in high-risk cardiovascular disease patients. MATERIALS AND METHODS: Patients with erectile dysfunction symptoms and candidates for andrology therapy were included (n = 112). Clinical data and endothelial nitric oxide synthase rs1799983 (G894T) and rs2070744 (T-786C), genotyped by fluorescence polarization assays, were registered. The 27-bp variable number of the tandem repeat polymorphism in intron 4 (intron4b/a) was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Association analyses were run with the R-3.2.0 software. RESULTS: A significant association between endothelial nitric oxide synthase 786-TT (p = 0.005) and the aa/ac of intron 4 variable number of the tandem repeat (p = 0.02) with higher erectile dysfunction susceptibility was observed in cardiovascular disease patients (60 ± 9 years, 66% severe erectile dysfunction, 56% ejection fraction). After 3-months of phosphodiesterase type 5 inhibitors, erectile dysfunction (International Index of Erectile Function, 50 ± 16 scores, the International Index of Erectile Function-Erectile Function 21 ± 10 scores, p < 0.001) and sexual quality of life (modified Sexual Life Quality Questionnaire 55 ± 23 scores, p < 0.001) had significantly improved. The cardiovascular ejection fraction was influenced positively with better sexual quality of life (0.1941), and also in the endothelial nitric oxide synthase G894-T allele (p = 0.076) carriers, which could merit future analyses. Erectile dysfunction was present as the primary clinical manifestation in 62% of cases, with cardiovascular disease occurring concurrently. Only former smokers and obese subjects debuted prior to cardiovascular disease than to erectile dysfunction. CONCLUSIONS: Our study provides comprehensive insights into the functional interaction linking endothelial nitric oxide synthase gene polymorphisms, erectile function, and ejection fraction in high-risk cardiovascular disease patients. Future therapeutic strategies could target endothelial nitric oxide synthase activity by including lifestyle changes and epigenetic modulations.

Circulating miRNA-21 is an innovative biomarker for cardiovascular events in erectile dysfunction patients.

Introduction: It is well-known that circulating microRNAs (miRNAs) play a relevant role in many kinds of diseases by regulating the expression of genes involved in various pathophysiologic processes, including erectile dysfunction (ED) and cardiovascular diseases (CVD). Purpose: This study aimed to identify the miRNA-21 profile in the blood samples of patients with ED, CVD, and the combination of both pathologies to elucidate the potential function of miRNA-21. Methods: A total of 45 patients with CVD and/or who underwent the erectile function test were included and divided into the following categories: CVD with ED (cases, n = 29) and controls (n = 16) with either ED or CVD. Real-time polymerase chain reaction analysis verified the results. miRNA-21 expression was quantified, and informatics analysis was applied to predict the functions of this differentially expressed miRNA-21. Results: A total of 64% of cases (63 ± 9 years, 66% with severe ED, 56% with CV ejection fraction) first presented ED as the sentinel clinical manifestation. Serum miRNA-21 levels in the control ED were significant, up to 10-fold higher than in the CVD controls and cases. A significant inverse (p = 0.0368, ß = -2.046) correlation was found between erectile function and miRNA-21 levels. Conclusions: Our study provides comprehensive insights into the functional interaction between miRNA-21 and ED in CVD patients. Its relevance lies in the potential of miRNA as a biomarker to be applied in the cardiovascular predictive medicine field.

[Predictive validity of the risk SCORE model in a Mediterranean population with arterial hypertension]. / Validez en la predicción de riesgo de la escala SCORE en una población mediterránea con hipertensión arterial.

INTRODUCTION AND OBJECTIVES: Hypertension is the most prevalent risk factor globally. Calculation of cardiovascular risk in hypertensive patients before initiation of treatment is recommended. This study aimed to assess the predictive value and clinical utility of the SCORE scale in preventing cardiovascular events and all-cause mortality in patients with hypertension. METHODS: Patients with hypertension from the ESCARVAL-RISK cohort were included. Cardiovascular risk was calculated using the SCORE scale. All deaths and cardiovascular events were recorded during a 5-year follow-up period. Sensitivity, specificity and predictive values were calculated for different cut-off points and the effect of different risk factors on the diagnostic accuracy of SCORE charts were assessed. RESULTS: In a final cohort of 9834 patients, there were 555 cardiovascular events and 69 deaths. The recommended risk value for initiating drug treatment (5%) had a specificity of 92% for death and 91% for cardiovascular events, and a sensitivity of 20% for death and 22% for cardiovascular events. In addition, the scale classified 80.4% of patients who experienced a cardiovascular event and 78.3% of those who died as low risk. Age, body mass index, retinopathy and anticoagulant therapy were associated with reduced predictive ability of the SCORE scale, while being female was associated with better risk prediction. CONCLUSIONS: The predictive ability of the SCORE scale for cardiovascular disease and total mortality in patients with hypertension is limited.

Impact of the Spanish consensus for improving lipid control on patients admitted for an acute coronary syndrome.

INTRODUCTION: In 2020, the Spanish Society of Cardiology published a consensus to improve lipid control in secondary prevention patients. This study was aimed to assess the impact of the implementation of this consensus in clinical practice. METHODS: Non-interventional, national and multicenter study, with a prospective and retrospective design in two cohorts. Implementation of the consensus was performed on the prospective cohort. Prospective cohort included patients with acute coronary syndrome (ACS) from December 2020 to March 2022 and were followed-up for 3 months. Retrospective cohort included patients with ACS in the same hospital, matched for main baseline clinical characteristics, between August 2019 to February 2020, with a follow-up of 3 months. Additionally, patients were included if they had previously received lipid-lowering therapy and LDL cholesterol (LDL-C) was >55 mg/dL. RESULTS: A total of 516 patients were included (245 in the prospective cohort and 271 in the retrospective cohort). Overall, mean age was 67.9 ± 11.4 years, 73.8 % were men, and 35.8 % had diabetes. At discharge, 98.4 % and 98.9 %, respectively (P = 0.71) were taking statins (90.6% vs 88.9 %; P = 0.564 high intensity statins), 58.4% vs 33.2 %; P<0.001 ezetimibe, 1.2% vs 0.4 %; P = 0.35 PCSK9 inhibitors. During the follow-up, the dose of statins was increased in 11.4% vs 3.3 % (P<0.001), and ezetimibe was added in 25.7% vs 25.8 % (P = 0.976). At study end, significantly more patients achieved LDL-C <55 mg/dL in the prospective cohort (45.6% vs 33.5 %; P = 0.013). CONCLUSIONS: The implementation of the Spanish lipid consensus was associated with a significant improvement of LDL-C control after only 3 months.

[Environment and cardiovascular health: causes, consequences and opportunities in prevention and treatment]. / Medio ambiente y salud cardiovascular: causas, consecuencias y oportunidades en prevención y tratamiento.

The environment is a strong determinant of cardiovascular health. Environmental cardiology studies the contribution of environmental exposures with the aim of minimizing the harmful influences of pollution and promoting cardiovascular health through specific preventive or therapeutic strategies. The present review focuses on particulate matter and metals, which are the pollutants with the strongest level of scientific evidence, and includes possible interventions. Legislation, mitigation and control of pollutants in air, water and food, as well as environmental policies for heart-healthy spaces, are key measures for cardiovascular health. Individual strategies include the chelation of divalent metals such as lead and cadmium, metals that can only be removed from the body via chelation. The TACT (Trial to Assess Chelation Therapy, NCT00044213) clinical trial demonstrated cardiovascular benefit in patients with a previous myocardial infarction, especially in those with diabetes. Currently, the TACT2 trial (NCT02733185) is replicating the TACT results in people with diabetes. Data from the United States and Argentina have also shown the potential usefulness of chelation in severe peripheral arterial disease. More research and action in environmental cardiology could substantially help to improve the prevention and treatment of cardiovascular disease.

Early carbohydrate antigen 125 as a mortality predictor in hospitalized patients with coronavirus disease 2019.

Background: Carbohydrate antigen 125 (CA125) is an indicator of inflammation, immune response, and impaired cardiac function. The aim was to investigate whether CA125 behaves as a biomarker of severity and poor clinical outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods: Serum CA125 [Elecsys CA125 II assay-(Roche Diagnostics GmbH)] was measured in stored biobank samples from COVID-19 hospitalized patients between 01 March 2020 and 17 October 2021. Multiple logistic regression models were built to explore the association between CA125 and clinical outcomes [in-hospital all-cause mortality, need for invasive mechanical ventilation (IMV), or non-invasive respiratory support (non-IRS)], estimating odds ratios (ORs; 95% CI). The gradient of risk of CA125 was evaluated by fractional polynomials. Results: A total of 691 patients were included, median age of 63 years (50-76), men (57.2%), with high comorbidity. At admission, 85.8% had pneumonia. Median CA125 was 10.33 U/ml (7.48-15.50). The in-hospital mortality rate was 7.2%. After adjusting for confounding factors, CA125 ≥ 15.5 U/ml (75th percentile) showed an increased risk of death [OR 2.85(1.21-6.71)], as age ≥ 65 years, diabetes, and immunosuppression. Furthermore, CA125 as a continuous variable was positive and significantly associated with the risk of death after multivariate adjustment. The mean hospital stay of the patients with CA125 ≥ 15.5 U/ml was longer than the rest of the study population. Conclusion: CA125 in the first 72 h of hospital admission seems a useful biomarker of mortality in hospitalized patients with moderate-severe COVID-19. If our findings are confirmed, the wide availability of this biomarker would make easy its widespread implementation in clinical practice.

Environment and cardiovascular health: causes, consequences and opportunities in prevention and treatment.

The environment is a strong determinant of cardiovascular health. Environmental cardiology studies the contribution of environmental exposures with the aim of minimizing the harmful influences of pollution and promoting cardiovascular health through specific preventive or therapeutic strategies. The present review focuses on particulate matter and metals, which are the pollutants with the strongest level of scientific evidence, and includes possible interventions. Legislation, mitigation and control of pollutants in air, water and food, as well as environmental policies for heart-healthy spaces, are key measures for cardiovascular health. Individual strategies include the chelation of divalent metals such as lead and cadmium, metals that can only be removed from the body via chelation. The TACT (Trial to Assess Chelation Therapy, NCT00044213) clinical trial demonstrated cardiovascular benefit in patients with a previous myocardial infarction, especially in those with diabetes. Currently, the TACT2 trial (NCT02733185) is replicating the TACT results in people with diabetes. Data from the United States and Argentina have also shown the potential usefulness of chelation in severe peripheral arterial disease. More research and action in environmental cardiology could substantially help to improve the prevention and treatment of cardiovascular disease.

Cardiovascular prevention in elderly patients.

In recent decades, life expectancy has been increasing significantly. In this scenario, health interventions are necessary to improve prognosis and quality of life of elderly with cardiovascular risk factors and cardiovascular disease. However, the number of elderly patients included in clinical trials is low, thus current clinical practice guidelines do not include specific recommendations. This document aims to review prevention recommendations focused in patients ≥ 75 years with high or very high cardiovascular risk, regarding objectives, medical treatment options and also including physical exercise and their inclusion in cardiac rehabilitation programs. Also, we will show why geriatric syndromes such as frailty, dependence, cognitive impairment, and nutritional status, as well as comorbidities, ought to be considered in this population regarding their important prognostic impact.

Psychological State after an Acute Coronary Syndrome: Impact of Physical Limitations.

The aim of this study was to investigate how physical limitations after ACS influence patients' quality of life and health perception. This was a longitudinal clinical study. We recruited 146 patients diagnosed with ACS. The patients performed a stress test (Bruce's protocol) for the evaluation of physical limitations and were classified according to the test result: without physical limitations (more than 10 METS), with some physical limitations (7 to 9 METS), and with high physical limitations (less than 6 METS). Significant differences were found between the three groups immediately after the diagnosis of ACS and after a period of three months, regarding health perception, anxiety, depression, sexual relationships, distress, and adjustment to disease. These differences resulted larger between the group with less limitations and the group with higher limitations. After 3 months, however, there was an overall improvement in all variables. In conclusion, physical limitations after ACS seem to influence perceived quality of life determined by measuring general health, vitality, total adaptation, emotional role, social adaptation, depression, and anxiety. Therefore, the highest the physical limitations, the poorer the psychological conditions and vice versa, even 3 months after ACS diagnosis.

Analysis of the prescription process of PCSK9 inhibitors in the cardiology departments of Spanish hospitals and optimization proposal. The IKIGAI study. / Análisis del proceso de prescripción de inhibidores PCSK9 en los servicios de cardiología de los hospitales españoles y propuesta de optimización. Estudio IKIGAI.

AIMS: To ascertain the formalities and procedures required for the prescription of PCSK9 inhibitors in the cardiology departments of Spanish hospitals, making proposals for improvement to optimize the prescription process. METHODS: A first phase of collecting information about the variables and administrative procedures required for the prescription of PCK9 inhibitors and the elaboration of a specific questionnaire and a second phase of collecting data with an online self-administered questionnaire. RESULTS: A total of 88 hospitals participated in the study (mean number of beds 625; mean number of cardiologists 18 ± 10; 78% university hospitals). There was underuse of PCSK9 inhibitors (real prescription of 30 treatments/year; potential prescription of 80), mainly because of not fulfilling the therapeutic positioning report (52%) and application refusal (31%). Beyond the requirements of the therapeutic positioning report, 1.2 ± 0.4 applications are required with 8.5 ± 4.2 variables. Only 21% of hospitals did not require a previous authorization process and in the remaining hospitals, approval from a committee was necessary. The accumulated time of the prescription process was 6 weeks. Discontinuation rates during follow-up were 9% ± 12%. CONCLUSIONS: Treatment with PCSK9 inhibitors is clearly underused in Spain. This is mainly due to both inappropriate identification of patients, and complex administrative procedures that could inhibit/discourage prescription by cardiologists and consequently, limit their use. In addition, there is a substantial delay from drug approval tadministration.

[Erectile dysfunction in patients with cardiovascular disease and the potential influence of genetic markers]. / Disfunción eréctil en pacientes con enfermedad cardiovascular y potencial influencia de marcadores genéticos.

INTRODUCTION: The association between erectile dysfunction (ED) and cardiovascular disease (CVD) is well known, the latter being an early independent risk factor that can appear up to 5 years before the onset of cardiovascular symptoms. The enzyme endothelial nitric oxide synthase (eNOS) could be implicated in its pathophysiology as an endogenous vasodilator. Our objective was to analyse the influence of variants of the eNOS gene, in the response to treatment of ED, in patients with CVD. METHODOLOGY: Observational, prospective study in patients with ED of the Cardiac Rehabilitation Programme. Demographic variables were collected (International Index of Erectile Function (IIEF), quality of sexual life (mSLQQ), anxiety and depression (HAD), along with cardiovascular risk factors (CVRF). Genetic analysis of polymorphisms T-786C, G894T of the eNOS gene was performed by RT-PCR with TaqMan probe, and the data were analysed using SPSS 25. RESULTS: Patients (n = 35, 60.8 ± 8.44 years) showed a median CVD (IQR 1-3) with severe ED (IIEF-EF of 9.4 ± 6.73 points) and a low perception of their quality of sexual life (-19.4 ± 8.37 points). At the final visit (n = 15), there were 71% responders to treatment with iPDE5, with a significant improvement in their ED (IIEF = 49.4 ± 17.29, IIEF-FE = 18.5 ± 9.60 scores) and of their quality of sexual life (7 ± 12 scores), with a higher percentage of responders among the native homozygous genotypes -786-TT and 864-TT. CONCLUSION: Variants of the NOS3 gene could influence the response to iPDE5. Full analysis of the patient sample will be required to confirm these preliminary results.

First national registry on the effectiveness and safety of evolocumab in clinical practice in patients attended in cardiology in Spain. The RETOSS-CARDIO study. / Primer registro nacional sobre la efectividad y seguridad de evolocumab en la práctica clínica en pacientes atendidos en cardiología en España. Estudio RETOSS-CARDIO.

OBJECTIVE: To present the first registry used to analyse the clinical profile of patients treated with evolocumab in Spain, including the effectiveness on the lipid profile and safety in the «real world¼ setting. METHODS: Multicentre, retrospective, and observational study of patients starting treatment with evolocumab from February 2016 to May 2017 in clinical practice in Spanish cardiology units. RESULTS: A total of 186 patients (mean age 60.3 ± 9.8 years were included, 35.5% with familial hypercholesterolaemia, and 94.1% with a previous cardiovascular event) from 31 cardiology units. Baseline lipid profile: Total cholesterol 219.4 ± 52.2 mg/dL, LDL-cholesterol 144.0 ± 49.0mg/dL, HDL-cholesterol 47.7 ± 13.0mg/dL, and triglycerides 151.0 ± 76.2mg/dL. At the time of initiating evolocumab, 53.8% of patients were taking statins (50% had partial or total intolerance to statins), and 51.1% ezetimibe. In all cases, the dose of evolocumab used was 140 mg, mainly every 2 weeks (97.3%). Evolocumab compliance was high (92.3%). Treatment with evolocumab was interrupted in 6 patients (3.2%), with only 1 (0.5%) due to a probable side effect. Evolocumab significantly reduced total cholesterol (30.9% at week 2, and 39.3% at week 12; P<.001), LDL cholesterol (44.4% and 57.6%, respectively; P<.001), and triglycerides (14.8% and 5.2%, respectively; P<001), with no significant changes in HDL-cholesterol (6.7% and 2.0%; P=.14). CONCLUSIONS: In clinical practice, evolocumab is associated with reductions in LDL cholesterol, with nearly 60% after 12 weeks of treatment, and with low rates of interruptions due to side effects and high medication compliance. These results are consistent with those reported in randomised clinical trials.

Recommendations to improve lipid control. Consensus document of the Spanish Society of Cardiology.

T***he current control of low-density lipoprotein cholesterol among patients with atherosclerotic cardiovascular disease is very low and this is associated with an increase of cardiovascular outcomes. In addition, the latter this happens, the risk will be greater. This is mainly due to an insufficient use of the lipid-lowering therapy currently available. In fact, with current treatments (statins, ezetimibe and PCSK9 inhibitors), the majority of patients in secondary prevention should achieve low-density lipoprotein cholesterol goals. For these reasons, in this manuscript promoted by the Spanish Society of Cardiology we propose three simple and feasible decision-making algorithms that include the majority of clinical scenarios among patients with ischemic heart disease, with the double aim of attaining therapeutic goals in the majority of patients as soon as possible; in secondary prevention the magnitude of the benefit is risk- and time-dependent.

Extended dual antiplatelet therapy after acute coronary syndrome in Spain: Results from the EPICOR study.

INTRODUCTION: Real-world, country-specific studies of dual antiplatelet therapy (DAPT) duration among survivors of acute coronary syndrome (ACS) are important for improving long-term prognosis. AIMS: To investigate DAPT duration after hospital discharge for ACS in Spain. RESULTS: Data from patients enrolled in the Spanish cohort of the EPICOR (long-tErm follow-up of antithrombotic management Patterns In acute CORonary syndrome patients) study (NCT01171404) were analyzed for changes to antithrombotic medication up to 2 years postdischarge according to index event diagnosis and patient characteristics. Deaths, coronary events, and bleeding events were analyzed over the same period. Overall, a high proportion of patients remained on DAPT at 2 years (53.1%). Among patients who experienced any on-treatment bleeding event, almost two-thirds remained on DAPT at the end of follow-up. Patients >65 years, diabetic, or those that were medically managed were more likely to continue with DAPT until 2 years following discharge. At 2 years, the incidence of bleeding events requiring hospitalization was low compared with the incidence of coronary events (1.4% vs 6.6%). There was a numerical reduction in coronary events, but no increase in bleeding events, with DAPT continuation compared with single antiplatelet therapy. CONCLUSIONS: More than half of patients in this unselected cohort study remained on DAPT at 2 years following discharge for ACS. Continuation with DAPT was greater among patients with additional cardiovascular risk factors, which suggests that treating physicians in Spain prioritizes ischemic risk reduction over bleeding risk in patients with ACS, according to patient's risk profile.

[Spontaneous coronary artery dissection. An infrequent cause of acute coronary syndromes]. / Disección espontánea de arterias coronarias como causa infrecuente de síndromes coronarios agudos.

Spontaneous coronary artery dissection is a rare condition that may produce severe myocardial ischemia. The growth of indications for cardiac catheterization have led to an increment in the number of cases identified in patients with acute coronary syndromes. Because the therapeutic approach and prognosis are uncertain, doubts often arise regarding the optimal management of these patients. We describe here the clinical and angiographic characteristics of 7 patients with spontaneous coronary artery dissection, as well as treatment and follow-up.