Focus on risk factors and prediction

The present issue focuses on risk factors and their prediction, specifically in the field of cardiomyopathy, arrythmias, coronary artery and vascular diseases, and lipid and environmental issues. Low QRS voltages (LQRSVs) have been extensively reported as an electrocardiographic feature of a variety of cardiac and non-cardiac pathological conditions. For instance, it was discovered to be a marker for the biventricular variant of arrhythmogenic cardiomyopathy and to predict the presence of left ventricular involvement with significant fibrofatty myocardial replacement and scar. Because of this, LQRSV has important clinical implications, particularly in the context of pre-participation screening of athletes, which is primarily based on 12-lead electrocardiography (ECG). To date, however, little attention has been paid to the presence and significance of LQRSV in hypertrophic cardiomyopathy (HCM), which is a common cause of sudden cardiac death (SCD) and a primary focus of pre-participation cardiac screening for athletes. In this study, Pelliccia and co-workers1 compared the prevalence and clinical correlates of LQRSV between 197 consecutive HCM patients and 775 Olympic athletes. The prevalence of LQRSV in HCM may be comparatively high and has clinical significance over a medium-term follow-up period: it was associated with a worsening clinical course, including a decline in NYHA functional class, an increased incidence of stroke, and a new indication for ICD implantation. In contrast, LQRSVs are uncommon in athletes (2.3%), but when associated with exercise-induced arrhythmias, they may serve as a marker for the identification of underlying, asymptomatic cardiac disease. Regular alcohol consumption is a well-established risk factor for incident atrial fibrillation (AF). This relationship is dose dependent, and even moderate alcohol consumption is associated with an increased risk of AF. More recent evidence revealed that alcohol abstinence reduces AF recurrences and is associated with a decreased risk of stroke in patients with a history of habitual alcohol consumption. In this study, Frederiksen and colleagues2 examined the relationship between 5-year changes in self-reported alcohol consumption and the long-term risk of AF in a large Danish cohort. The consumption of more than 21 alcoholic beverages per week was associated with an increased risk of AF. Those who increased their alcohol consumption had a greater risk of AF than those who maintained a low or moderate intake. These findings support the significance of adopting a healthier lifestyle to reduce the prevalence of AF, as suggested by European guidelines. Coronary artery disease, especially myocardial infarction (MI), is one of the leading cardiovascular diseases with a high mortality rate. Modern reperfusion therapies, such as percutaneous coronary intervention (PCI) and thrombolytic therapy, are exclusively time dependent in the treatment of acute MI. There is a correlation between delayed treatment and a higher rate of morbidity and mortality. Therefore, minimizing the delay before initiating reperfusion therapy is a crucial strategy for increasing the treatment’s success rate. In this context, multiple characteristics, including older age, female gender, and diabetes, have been associated with prolonged pre-hospital delays at both patient and system levels. The purpose of a here-presented study was to identify predictors of pre-hospital delay in ST-elevation MI (STEMI) patients and to examine the evolution of this delay over nearly two decades in women and men in Switzerland:3 15 350 STEMI patients were analysed using multivariable quantile regression analysis. Between 2002 and 2019, the median delay was 150 min for men and 180 min for women. The median prehospital delay decreased substantially over time for both sexes, but the trend was more pronounced for women. In particular, the unadjusted sex differences in delay fell from 60 min in 2002 to 40.5 min in 2019. Even after adjustment, the multivariable model revealed a significant interaction between gender and admission year, indicating that the reduction in delay was greater for women than for males. Each year, between 1% and 3% of adults present with chest pain for the first time in primary care. Many patients do not receive a specific diagnosis and are considered to have an unattributed cause for their chest pain. However, these patients have a higher prevalence of risk factors for future cardiovascular events than the general population, and a higher incidence of cardiovascular disease in the future than those without chest pain. In this context, the identification of those who have the greatest risk of future cardiovascular events would allow targeting of key modifiable cardiovascular risk factors with preventative management. The study of Jordan and colleagues4 aims to (i) evaluate the performance of a general population risk prediction model (QRISK3) in this population, (ii) identify key risk factors for cardiovascular disease in patients with unexplained chest pain in primary care in the United Kingdom, and (iii) derive and validate improved prediction models for cardiovascular disease in these patients. The strongest cardiovascular disease risk factors were diabetes, AF, and hypertension. Males, patients of Asian descent, those living in more impoverished areas, obese patients, and smokers were at a greater risk. The final developed model had excellent predictive performance (external validation c-statistic of 0.81, calibration slope of 1.02) while QRISK3 underestimated cardiovascular risk in this population. Women and men have different cardiovascular disease epidemiology, management, in-hospital, and long-term outcomes. Current recommendations do not address sex-related concerns since women are underrepresented in clinical trials. Reports regarding sex heterogeneity in acute aortic dissection (AAD) are incomplete and in part contradictory; therefore, gender differences in clinical features, management, and outcomes were investigated among patients with type A AAD in a systematic review and meta-analysis.5 Here, the authors confirmed that also in AAD, there is a sex phenotype. In fact, type A AAD females were older than males but had a lower body mass index, body surface area, and plasma creatinine concentration. The prevalence of active smoking, bicuspid aortic valve, and previous cardiac surgery was lower among women, whereas the prevalence of diabetes was higher. In addition, women experienced pericardial effusion/cardiac tamponade more frequently than men. Interestingly, surgical mortality in hospitals did not differ by gender whereas 5- and 10-year survival rates were higher among men. Lower extremity arterial disease (LEAD) affects >230 million adults worldwide and is associated with increased risk of various adverse clinical outcomes (other cardiovascular diseases such as coronary heart disease and stroke and leg outcomes such as amputation). A growing amount of research suggests that LEAD is closely linked to mortality, primarily because it is a reliable indicator of future MI and stroke. Critical limb-threatening ischaemia (CLTI) and lower extremity amputation are two catastrophic limb-related consequences linked to LEAD. Guidelines from the European Society of Cardiology (ESC) and the European Society for Vascular Surgery (ESVS) advise lipid-lowering medications for all patients with LEAD, anti-thrombotic medications if symptomatic, and anti-hypertensive medications if hypertensive, where angiotensin receptor blockers and converting enzyme inhibitors should be considered first-line medications, to reduce the cardiovascular risk. However, there is a serious undertreatment of LEAD patients with evidence-based medical therapy (EBM), according to several research. In this issue of the journal, Bager et al.,6 using data from Danish national registries, aimed to describe trends in practice patterns of EBM in CLTI patients and compare EBM use between CLTI and MI patients. They discovered that despite similar treatment recommendations, CLTI patients were undertreated and had a greater risk of cardiovascular complications and death compared with MI patients. Atherosclerosis is a chronic inflammatory disease of the subintimal layer of large- and medium-sized arteries that result in the formation of fibrofatty lesions through the interaction of numerous well-established risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus, and smoking. Atherosclerosis is also a hallmark of the vascular ageing (VA), a process that can capture the early (generally asymptomatic) features of vascular degeneration. VA encompasses the cumulative effect of all cardiovascular risk factors on the arterial wall over the life course and thus may help identify those at elevated cardiovascular risk, early in disease development. Although the concept of VA is gaining interest clinically, it is seldom measured in routine clinical practice due to the lack of consensus on how to characterize VA as physiological vs. pathological and various practical issues. The review from Climie and colleagues addresses several questions about VA such as how to measure it in clinical practice, to raise awareness among the larger medical community, and to move routine VA measurement a little closer to the bedside from the bench.7 Globally, cardiovascular disease is the primary cause of disease burden. The number of patients with cardiovascular disease increased to 523 million in 2019 and accounted for roughly one-third of global annual fatalities. Currently, alongside the classic risk factors, environmental factors such as air pollution or socio-economic status play a crucial role in the development of cardiovascular diseases. Here, Yang and colleagues examined the association between multiple living environmental factors and cardiovascular diseases. During the 7-year follow-up, they discovered that a poor living environment, including a higher level of ambient PM2.5, solid fuel use, non-tap water use, and residing in one-story buildings, was a risk factor for cardiovascular disease.8 Elevated low-density lipoprotein (LDL) cholesterol is a potent cause of heart attack and stroke, and lowering LDL cholesterol reduces the risk of cardiovascular disease. To prevent cardiovascular disease, ESC guidelines recommend reducing LDL cholesterol levels as much as feasible. The systematic review and meta-analysis from Sawant and Wang investigated the effect of lipid-lowering medication on cardiovascular disease according to ethnicities and regions in previously published randomized clinical trials.9 A total of 53 trials with 329 897 participants were included in the analysis. The average age was 62 years and 73% were men. Regarding regions, 39.5% of participants were from Europe, 16.0% were from North America, 9.0% were from Japan, 2.8% were from Australasia (Australia and New Zealand), 1.8% were from South America, 1.1% were from Asia, 0.6% were from South Africa, and 29.2% were unspecified. Lowering LDL cholesterol reduced the risk of MACE in all regions, by 20% globally, 25% in Australasia, 25% in North America, 24% in the United States, 24% in Europe, and 27% in Japan. In studies reporting outcomes by ethnicity, lowering LDL cholesterol was associated with risk reductions of 45% in Blacks and 27% in Japanese. These results underscored the lack of recruitment of minority groups, such as those from South Africa, South America, and Asia, as well as those of African, Latino, and Asian descent, while indicating that the benefits of lowering LDL cholesterol are universal. Dyslipidaemia continues to play a significant role in higher cardiovascular risk. There are still considerable residual risks among those on statins, even in those with low LDL-C levels, even though the clear advantages of LDL-lowering medicines have been addressed for decades. The atherogenic role of triglycerides, triglyceride-rich lipoprotein (TRL), and remnant cholesterol (RC), which have been reported to promote cardiovascular risk, has recently come under research attention given that strategies to increase high-density lipoprotein cholesterol (HDL-C) have failed to reduce cardiovascular events. Here, the researchers inferred that RC measures would be more accurate predictors of incident risk than LDL-C values alone.10 Utilizing population-based data from the entire country of Korea, they looked into the independent relationship between RC levels and cardiovascular disease incidence in various subgroups. The following are the main conclusions. First, 19% of all individuals were in the high-remnant-C–alone group (LDL-C < 3.4 mmol/L, RC > 0.8 mmol/L), which was linked to a higher risk. Second, even after taking into account other factors, such as LDL-C levels, RC levels still correlated with the probability of developing incident cardiovascular disease. Finally, compared with each factor acting independently, LDL-C and RC worked together synergistically to increase the risk. None declared.