Editors’ presentation: focus on cardiovascular risk assessment

Risk assessment is a critical step in the approach to prevention of atherosclerotic cardiovascular disease (ASCVD). Several studies have been conducted so far to develop tools for cardiovascular risk assessment in Europe but given the large variation in the ASCVD burden between different regions, it should be emphasized that a single tool for risk estimation is not enough accurate, and it would be ideal if each community could develop its own model based on more recent and local data.1 In this issue of the journal are presented two studies, one from Spain and another from Switzerland which compare a local risk score with the European SCORE in risk assessment. Fernández-Labandera et al.2 here present the IberScore model for its development, they recruited 992 523 healthy workers in Spain, over the time period 2004–09 and divided the sample into two independent cohorts: a derivation cohort (626 515 workers from 2004 to 2006) and a temporal validation cohort (366 008 workers from 2007 to 2009). They followed both cohorts over 10 years and registered all fatal and non-fatal ASCD events. The new model showed superior clinical utility compared to the European SCORE in predicting cardiovascular events. Likewise, Beuret et al.3 aimed to compare a Swiss (AGLA) and SCORE risk algorithm in predicting incident ASCVD and estimating statin eligibility in 6733 individuals, aged 35–75 years, with a 10-year follow-up in Switzerland. They showed that both algorithms presented similar accuracy but with a quarter of adults developing ASCVD not previously identified to be eligible for statin therapy. Low levels of high-density lipoprotein cholesterol (HDL-C) and high concentrations of low-density lipoprotein cholesterol (LDL-C) are traditionally related to a greater risk of ASCVD events.4 Recent research, however, found no evidence of a cardiovascular protective effect of elevated HDL-C levels in keeping with genetic studies. These newer concepts have lead to reconsider the functional properties of the HDL particle which may be significantly altered in the context of an inflammatory milieu, transforming the particle from a vaso-protective and anti-atherogenic particle to a noxious pro-atherogenic equivalent. The review by Ratick et al.5 discusses the relationship between HDL-C and ASCVD, explores the recent evidences regarding the changes in the composition and function of HDL in chronic inflammatory conditions and examines the potential for future HDL-modifying therapeutic interventions. The inflammatory processes represent a crucial step in the pathogenesis of atherosclerosis. In this context, increased levels of C-reactive protein (hs-CRP) and other inflammatory biomarkers are independently associated with a higher incidence of ASCVD.6 However, the significant impact of modifiable lifestyle risk factors (modRF) for coronary artery disease (CAD) on hs-CRP levels cannot be neglected. Here, Blaum et al.7 explored the association between modRF and inflammation in a hospital-based cohort study of patients with CAD in Germany. Their results present a promising approach in the management of CAD showing that modRF are strongly and independently associated with hs-CRP levels and an hs-CRP level <2 mg/L can be reached by lifestyle changes alone. There is an ongoing debate in the medical community regarding the effects of testosterone on cardiovascular health. Several trials have found an increased ASCVD risk with testosterone therapy. Contrary to this view, there is mounting evidence suggesting a possible cardioprotective effect of testosterone. In fact, normal physiologic levels of testosterone are beneficial to the male cardiovascular system and testosterone deficiency is associated with an unfavourable metabolic profile, including increased adiposity, insulin resistance, loss of bone and lean body mass, diabetes (DM), and adverse events, such as acute coronary syndrome, atrial fibrillation, and stroke.8 Furthermore, testosterone levels correlate positively with HDL and negatively with LDL and the inflammatory state. To date, despite the large amounts of studies confirming the beneficial effects of testosterone no causal association has been proved, and results are conflicting. This is particularly evident in patients with ASCVD in which the presence of potential confounders, such as smoking, diabetes, and hypertension, could influence the relationship between testosterone and cardiovascular events. Here, the study by Gencer et al.9 investigated the prevalence of low testosterone in a large cohort of CAD patients and the impact of this lab finding on clinical outcomes. In brief, they found in almost 40% of men low total endogenous testosterone, which was not associated with mortality, after adjustment for high-risk confounders, such as pre-existing DM, inflammation, and GRACE score at hospital admission. There is an ongoing debate in the literature as to whether homocysteine (Hcy) is a causal risk factor for ASCVD, just a risk marker, or neither. A recent systematic review of 15 randomized controlled trials found no effects of Hcy‐lowering interventions on myocardial infarction, adverse events, or mortality. On other hand, other studies have demonstrated an association between elevated Hcy levels and coronary and valvular calcification that are associated with higher cardiovascular morbidity and mortality.10 Given this controversy, Miao et al.,11 using a two-sample Mendelian randomization, explored the relationship between plasma Hcy levels and CAD or acute myocardial infarction in a large European population. Using a genetic approach, they found that plasma Hcy levels were not causally associated with ASCVD or myocardial infarction. Mortality patterns among older adults with type 2 DM (DM2) are well-established whereas the evidence about the all-cause and cause-specific mortality among children and young adults with DM is scarce. In a large Swedish registry, those with DM2 onset at age <40 years had a two- to four-fold higher incidence of coronary events, strokes, and total mortality and a nearly five-fold greater risk for HF after 5.6 years of follow-up, compared with controls.12 Similarly, in a study from Australia, those with DM2 diagnosed before 40 years of age had a 2.5- to 3.5-fold higher standardized mortality ratio, after adjustments for DM duration. DM is now being diagnosed at younger ages, which points to the challenges presented by its long-term complications and premature mortality globally.13 Svane et al.14 examined all-cause and cause-specific mortality in children and young adults with and without DM. This is a nationwide study and included all persons in Denmark aged 1–35 years in 2000–09 and 36–49 years in 2007–09, which equals 27.1 million person-years. In brief, the authors showed that young adults with DM had four-fold increased all-cause mortality and eight-fold increased ASCVD mortality compared with persons without DM pointing out the need for a more stringent cardiovascular risk control among younger persons. Although a causal relationship between short sleep duration and cardiovascular risk is not confirmed a number of studies demonstrated that sleep problems such as excessive (short or long) sleep durations or poor sleep quality may increase the overall risk of ASCVD and all-cause mortality. However, is still debated whether the relationship between short sleep duration and cardiometabolic disorders is monodirectional or bidirectional. In other words, the prevalence of cardiometabolic disorders is higher in short sleepers than in normal sleepers, but whether short sleep time can be caused by the presence of a cardiometabolic disorder remains unresolved.15 Here, the clinical review by Spiesshoefer et al.16 provides an overview on the effects of sleep disturbances on cardiovascular health and discusses the main pathophysiological mechanisms that link short sleep duration to different vascular diseases and to increased cardiovascular risk. Furthermore, in the present issue of the journal, Li et al.17 showed that both work stress and impaired sleep are associated with CAD and ASCVD mortality in a large cohort of hypertensive workers in Germany. These two works confirmed that sleep should be considered modifiable risk factors and it should be placed next to diet and exercise as targets for a healthy lifestyle. Cardiorespiratory fitness (CRF) is defined as the ability to sustain dynamic exercise by large muscle groups over time at moderate to high-intensity levels. Numerous studies indicated an inverse relationship between CRF and mortality and incidence of many chronic diseases. Although the gold standard for measuring CRF is the cardiopulmonary exercise test (CPET), a vast majority of patients never had the opportunity to perform this test, making CRF the only major risk factor not optimally assessed in clinical practice. To overcome this limit, several non-exercise CRF prediction equations, mainly derived from age, sex, and anthropometric variables, have developed. However, these equations have several important limitations: they do not account for the well-known genetic influence on CRF and they rely also on self-report variables.18 In this issue of the journal Peterman and co-authors compared the accuracy of non-exercise prediction equations to directly measured CRF and evaluated their ability to classify an individual’s CRF.19 The authors showed that estimated values of CRF calculated from the 28 distinct non-exercise prediction equations were statistically different from directly measured CRF thus reducing their potential clinical utility and confirming the central role of CPET in assessing CRF. Sarcopenia has been defined as an age-dependent progressive skeletal muscle disorder that involves the loss of muscle mass and function. Sarcopenia affects a large proportion of elderly patients and is associated with multiple adverse outcomes including falls, metabolic disorders, frailty, disability, and mortality.19 Moreover, several cross-sectional studies have demonstrated a close association between sarcopenia and other cardiovascular diseases such as myocardial infarction and atrial fibrillation. The Timed Up and Go test (TUG) is a reliable and valid test for quantifying functional mobility in older adults and it could be used in predicting sarcopenia. Chun et al.20 evaluated the prognostic power of TUG test performance in a retrospective cohort study which including more than 1 million participants aged 66 years and they showed that slower TUG speed was associated with an increased risk of developing myocardial infarction, heart failure, and all-cause mortality in older adults. These data confirmed once again that one of the main goals of preventive programmes in ageing patients should be the preservation of mobility and to avoid sarcopenia.21 Conflict of interest: none declared. The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Preventive Cardiology or of the European Society of Cardiology.