Focus on cardiovascular risk factor control

The present issue is focusing on risk stratification in different clinical and pathological conditions, including cardiovascular disease, diabetes, and cardiomyopathy. Practical information is provided to be implemented in clinical practice. Many patients still have a high risk of atherosclerotic cardiovascular disease (ASCVD), even though they are taking preventive treatments like statins as recommended by guidelines.1 This residual risk may be caused by high levels of triglyceride-rich lipoproteins, which have been linked to the development of ASCVD. The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) recently found that lowering triglycerides with 2 g of icosapent ethyl twice a day reduced the risk of ASCVD events in statin-treated patients with high plasma triglycerides despite low-to-moderate low-density lipoprotein cholesterol (LDL-C) levels. However, how to select individuals with increased triglycerides who are most likely to benefit from further risk-reducing therapy with icosapent ethyl remains uncertain. In this context, it has been demonstrated that calculating the coronary artery calcium (CAC) improves risk prediction beyond what is possible with standard risk factors. In this issue of the journal, Mortensen and coworkers aimed to determine whether plaque burden as assessed by CAC could stratify ASCVD risk among patients eligible for icosapent ethyl.2 They studied 2146 individuals and during a median follow-up period of 4.3 years, 146 ASCVD events occurred: an incremental increase in ASCVD event rates was associated with CAC scores increase. The evaluation of CAC might help identify individuals with lower and greater ASCVD risk, independent of obstructive vs. non-obstructive coronary status. The predicted 5-year NNT to prevent one events with icosapent ethyl varied significantly across rising CAC score groups, ranging from 87 in patients with CAC = 0–17 in patients with CAC 300. Carotid ultrasonography is a noninvasive, nonradioactive, and reproducible imaging technique used to detect carotid atherosclerosis and screen people at high risk for ASCVD. Carotid intima-media thickness (CIMT) and carotid plaque presence predict ASCVD events but the clinical use of carotid ultrasonography for additional risk stratification in moderate-to-high-risk ASCVD patients is not supported by strong evidences and recommendations.3 In addition, the prognostic value of carotid ultrasound in high-risk patients with established ASCVD has not been examined. Here, Georgiopoulos et al. aimed to identify and externally validate optimal prognostic thresholds of cumulative markers of advanced carotid subclinical atherosclerosis in high ASCVD risk patients.4 They analysed high or very high ASCVD risk patients from a cardiovascular prevention registry (n = 751, derivation cohort) and from the Atherosclerosis Risk in Communities study (n = 2897, validation cohort). CIMT excluding plaque, average maximal (avg.maxWT), maximal wall thickness (maxWT), and number of sites with carotid plaque were assessed. They found that in both the derivation cohort and the validation cohort, a maxWT >2.00 mm and avg.maxWT >1.39 mm offered incremental prognostic value, improved discrimination, and correctly reclassified risk over the clinical ESC risk SCORE. Elevated LDL-C is one of the key cardiovascular risk factors, according to epidemiologic and genetic studies. Additionally, there is strong evidence that lowering LDL-C can lower cardiovascular risk. Therefore, guidelines issued by major societies recommend moderate-to-high intensity statin therapy for individuals who are at high risk of ASCVD, including patients with chronic kidney disease (CKD). However, the findings of studies examining the effects of statin use in patients on haemodialysis are conflicting. In fact, SHARP (Study of Heart and Renal Protection) showed that moderate intensity statin therapy in combination with ezetimibe reduced the risk of major atherosclerotic events in patients with CKDs, including those on dialysis while other randomized clinical trials (AURORA and 4D) failed to show significant benefits of statin therapy in their primary outcomes. Variability in cholesterol absorption may be a contributing factor. Post hoc analysis of the 4D study indicated that high cholesterol absorption was related with an elevated cardiovascular risk and that atorvastatin would lower cardiovascular risk in haemodialysis patients with low cholesterol absorption, but not in those with high cholesterol absorption. In this study, the authors sought to evaluate baseline non-cholesterol sterols in the AURORA trial to further investigate the role of cholesterol metabolism in haemodialysis patients. In brief they confirmed that haemodialyzed patients with high cholesterol absorption and low cholesterol synthesis have an elevated risk of cardiovascular disease, with no differences between genders.5 Elevated body mass index (BMI) and hypertension are recognized risk factors for atrial fibrillation (AF).6,7 Long-term changes and variations in weight and blood pressure, measured using the mean of repeated measurements, are related to the onset of AF. However, it is still unknown how different longitudinal patterns of obesity or hypertension affect AF risks at the population level. Here, the sex-specific longitudinal trajectories of obesity-related variables and blood pressure at the population level and their correlations with the incidence of new-onset AF were evaluated using data from the large prospective population-based Rotterdam study. It was showed that different longitudinal trajectories of obesity and blood pressure were linked to new-onset AF in both men and women: the largest risks for incident AF were conferred by increasing weight and BMI trajectories in both men and women while individuals who are overweight and lose weight may experience fewer AF incidents.8 Diabetes mellitus (DM) raises the incidence of AF and having both AF and DM increases the risk of all-cause death and the burden of complications. Here, the prognosis regarding cardiovascular events, mortality, and dementia among patients with AF and different types of DM was evaluated and compared with those of individuals without DM. Among 309 611 patients with AF, the presence of DM, regardless of type, was related with an increased risk of premature death, cardiovascular events, and dementia. This increase was greater in Type 1 DM than in Type 2 DM. Instead a history of severe hypoglycaemia was linked to a poorer prognosis in Type 2 DM only.9 In order to give the most effective follow up and therapy in patients with cardiomyopathy, it is essential to identify the underlying aetiology.10 In fact, in these patients, disease progression may be more rapid and could necessitate more frequent follow up in patients with genetic mutation. In addition, the threshold for implanting a cardioverter defibrillator is lower in malignant LMNA-based cardiomyopathies and specialized enzyme replacement treatment could be an option in Fabry disease. Genetic testing in cardiomyopathies is currently recommended by the European Society of Cardiology and American College of Cardiology/American Heart Association. In this issue of the journal, Stava et al. described results from genetic testing for cardiomyopathies in a national laboratory for genetic testing in Norway since 2003. A potentially pathogenic or pathogenic variant was identified in 574 probands, corresponding to a genetic testing hit rate of 13.1% overall, 11.9% in hypertrophic, 14.2% in dilated, and 14.2% in arrhythmogenic right ventricular cardiomyopathy. About 43.2% were positive for the variant identified in their family.11