Editorial comments: Focus on clinical cardiology and risk factors

This special issue is dedicated to several topics related to cardiovascular clinical conditions and related risk factors. Data from the large registries such as the EURObservational Research Programme (EORP) of the European Society of Cardiology are also presented. Chronic coronary syndromes (CCSs) cover a wide range of clinical situations resulting from atherosclerotic plaque accumulation in the coronary arteries and continue to be a leading cause of death globally. Here, Kerneis et al.1 investigated the impact of CCS on cardiovascular hospitalization and mortality, based on a major European registry of CCS patients [European Society of Cacrdiology (ESC) EURObservational Research Programme Chronic Ischaemic Cardiovascular Disease Long-Term registry]. Between 2015 and 2018, the registry includes 9174 patients across 154 centres in 20 countries; 1-year follow-up data were available for 6655 (72.5%) participants. Patients had a median age of 67 years, 73% were male, and 30.2% had diabetes. Overall, 2.5% died within the first year of follow-up, and the cardiovascular disease (1.5%) was the leading cause of death. Women had a considerably greater cardiovascular death rate than men (2.0% vs. 1.3%, P = 0.04). In one year, 27.1% were hospitalized at least once, primarily for cardiovascular diseases (20.6%). The leading cause of hospitalization was coronary artery disease (11.2%), followed by heart failure (HF) (4.7%) and vascular reasons (2.0%). In a Cox regression analysis, comorbidities such as 40% left ventricular ejection fraction, stroke, and liver disease were independent predictors of cardiovascular death and hospitalization. Obesity and other anthropometric variables are well-established risk factors for the development of atrial fibrillation (AF).2 This relationship is recognized in the most current ESC guidelines for AF. However, there is a knowledge gap on how body shape and composition influence outcomes following the development of AF. In this issue of the journal, Boriani et al.3 in a large observational registry examined how differences in baseline anthropometry may be connected with AF patient outcomes. In particular, they examined height, weight, body mass index (BMI), body surface area (BSA), and lean body mass (LBM) in an unselected cohort of adults with recent onset of AF. In 10 220 individuals, regardless of sex, the lowest tertile of each measure was consistently related with poorer overall survival: patients in the lowest tertile for weight, BMI, BSA, and LBM were less likely to be prescribed antithrombotic therapy and tended to be older, with many comorbidities. Multivariable cox regression indicated that women in the highest tertile of weight and BSA and men in the top tertiles of BSA and LBM had better outcomes. Sleep disorders are associated with an increased risk of cardiometabolic problems.4 Aim of the study by Jia et al.5 was to specifically explore the occurrence of a causal link between sleep problems and cardiometabolic diseases. This was done by making use of two-sample Mendelian randomization analyses of sleep disorders focusing on their ability to determine cardiometabolic diseases including ischaemic stroke, coronary artery disease, HF, and type 2 diabetes mellitus. Genetic variants were selected as instrumental variables for self-reported daytime napping, daytime sleepiness, ‘morning person’, insomnia, short sleep duration, and long sleep duration from four European-descent genome-wide association studies including 2 500 086 participants. The inverse-variance weighted method was used to explore the role of sleep phenotypes in determining cardiometabolic diseases in the main analysis, followed by several sensitivity analyses for robustness validation. This study provides evidence that genetically predicted self-reported daytime napping, insomnia, and short sleep duration were causally associated with an elevated risk of cardiometabolic diseases. Moreover, also genetically determined self-reported daytime sleepiness and ‘morning person’ were shown to potentially have a negative influence on cardiometabolic risks. These results indicate sleep problems as promising targets for cardiometabolic diseases prevention. No definite evidence is available on the interaction between pain related to different chronic pathological conditions and cardiovascular disease. Aim of the study by Rönnegård et al.6 was to explore the association between different levels of chronic or non-chronic pain and risk of cardiovascular disease by considering data from 189 289 participants in the UK Biobank reporting pain at baseline. These individuals were divided into three groups according to pain severity (based on duration and widespreadness). Participants reporting no pain were controls. Multivariable Cox regression was used to investigate the association between pain and incidence of myocardial infarction, HF, stroke, cardiovascular mortality, and composite cardiovascular diseases. By considering a median of 7.0 years’ follow-up, chronic pain was found associated with an increased risk for myocardial infarction, stroke, HF, and cardiovascular death independent of established cardiovascular risk factors, socioeconomic factors, co-morbidities, and medication. These data, on the possible role of chronic pain as an underestimated cardiovascular risk factor, may have important public health implications. The effect of alcohol consumption on coronary heart disease (CHD) is still unclear.7 Observational studies have demonstrated that compared with no consumption, light to moderate alcohol consumption is associated with a reduced risk of clinical CHD, whereas there is less evidence of a protective effect on subclinical CHD as measured by coronary artery calcification. Given the inability to run a randomized trial to confirm or refute the effect of alcohol consumption on CHD, an alternative approach is to use a genetic variant as a proxy for alcohol consumption. The single-nucleotide polymorphism (SNP) rs671 in the aldehyde dehydrogenase 2 gene (ALDH2), which encodes the ALDH2 enzyme, provides the primary pathway of alcohol metabolism. The ALDH2-rs671 variant, common only in East Asian populations, greatly slows acetaldehyde breakdown, causing severe discomfort that strongly reduces alcohol consumption. This can lead to selection of the SNP rs671 as a genetic instrument in Mendelian randomization analysis. The genetic findings of the ALDH2-rs671 variant on cardiovascular risk factors or outcomes in men have been shown to be driven by alcohol exposure. Aim of the paper by Hisamatsu et al.8 was thus to investigate the causal role of alcohol intake in relation to subclinical and clinical CHD in two Mendelian randomization studies using the ALDH2-rs671 variant. The first study was a cross-sectional study of coronary artery calcification on computed tomography of 1029 healthy men, while the second study was a case–control study of 421 men with CHD (acute coronary syndrome or stable angina pectoris) who underwent coronary revascularization and 842 age-matched male controls. Results of these analyses indicate a positive association of alcohol consumption with coronary artery calcification burden but an inverse association of alcohol consumption with clinical CHD, especially acute coronary syndrome. These findings provide new hypothetical insight into how alcohol may reduce the risk of clinical CHD, by introducing alterations in the plaque composition of the coronary artery from lipid to fibrous tissue with calcification and thus decreasing the plaque vulnerability to rupture, thereby decreasing the risk of clinical CHD. Over the years, several risk scores have been proposed to predict mortality in patients with HF. Aim of the study by Siddiqi et al.9 was to assess the performance of risk scores validated for mortality prediction in patients with acute HF (AHF) and chronic HF (CHF). This was done through a MEDLINE and Scopus search for studies addressing this issue from January 2015 to January 2021. Nineteen studies were found, including 11 risk scores. Data from 494 156 patients were considered, focussing respectively on AHF (n = 24 762), CHF mid-term mortality (n = 62 000), and CHF long-term mortality (n = 452 097) and analysed to estimate discrimination and calibration of the scores used. Discrimination is defined as the ability of a risk model to determine whether an individual will experience the outcome of interest in the pre-specified follow-up duration and is evaluated by the C-statistic (C-index or AUC). Calibration refers to the ability of a risk model to accurately predict the absolute risk level of the outcome of interest and is evaluated though different approaches. Overall, discrimination of the evaluated risk scores was good across the three subgroups: AHF mortality (C-index 0.76), CHF mid-term mortality (1 year; C-index 0.74), and CHF long-term mortality (≥2 years; C-index: 0.71). The Spanish score in patients with acute heart failure (MEESSI-AHF, C-index 0.81) and the Machine Learning Assessment of RisK and EaRly mortality in Heart Failure score (MARKER-HF, C-index 0.85) had an excellent discrimination for AHF and CHF mid-term mortality, respectively, while the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI score had good discrimination, C-index 0.78) for CHF long-term mortality as compared to other scores. Overall, risk scores predicting short-term mortality in AHF did not have evidence of poor calibration, while those predicting mid-term and long-term mortality in CHF varied in calibration performance. The results of this study, showing good discrimination for mortality of most HF risk scores, but modest reporting of calibration, and current lack of head-to-head comparisons of these scores in same populations, emphasize the need of additional studies to improve our prediction of outcome in HF patients. Abdominal aortic aneurysm (AAA) disease accounts for 1% of all deaths among those aged 65 years and older. In these patients, preventive medical therapy can reduce the incidence of atherosclerotic vascular events and premature death. Consequently, modifying risk factors and altering one's lifestyle is a significant objective of AAA management. In this context, cardioprotective drugs, such as statins, aspirin, and antihypertensive therapies, have been associated with a 20–35% decreased risk of all-cause mortality among patients with AAA, regardless of the repair status of the AAA. In the current issue of the journal, Nicolajsen et al.’s10 work has given light on the present prevalence of AAA and the extent to which preventive medications are integrated into ordinary clinical practice. During the 1999–2003, 2004–2008, 2009–2013, and 2014–2018 monitoring periods, prevalence and incidence of AAA increased, while rupture rate dropped. Similarly, the incidence of atherosclerotic cardiovascular illnesses decreased across the four observation periods, in parallel with an increase in the use of statins, antiplatelets agents and combined therapy with both antiplatelets and statins. However, the utilization of these cardioprotective therapies did not increase further after 2013, and half of the AAA patients still did not receive concomitant medical therapy with statin and antiplatelet therapy during the 2014–2018 period. In conclusion, these findings greatly contribute to our understanding of the clinical characteristics and prognosis of AAA patients, and they demonstrate that substantial opportunities exist to optimise cardioprotective treatment. Transgender healthcare is a rapidly growing field of medicine, whose aim is to assist transgender individuals with adjustments of primary and secondary sexual characteristics to align with their gender identity. Gender dysphoria (GD) diagnosis refers to the distress caused in many transgender individuals by the marked incongruence between their gender identity and their birth-assigned sex. Over the last decades, there is increasing interest regarding potential adverse health outcomes among transgender individuals, with special focus on cardiovascular outcomes, also related to the gender-affirming therapies, which includes gender-affirming hormone treatment (GAHT), surgical therapy, or both, depending on individual needs. Here, an analysis of the Swedish Healthcare registry led to the identification of 1779 transgender individuals [48% birth-assigned males (AMAB), 52% birth-assigned females], but only 18 developed cardiovascular disease, most of which were conduction disorders, in a 10-year follow-up. Thus, the risk of cardiovascular disease among GD individuals was low, although increased compared with matched individuals without GD: 2.4 times higher in AMAB individuals compared with cisgender women and 1.7 higher compared with cisgender men. Furthermore, no support for a causal relationship between GAHT treatment and CVD outcomes.11