The Year in Cardiology 2015: Prevention

M. John Chapman; Stefan Blankenberg; Ulf Landmesser


Eur Heart J. 2016;37(6):510-519. 

In This Article

Abstract and Introduction


The prevention of CVDs represents an enormous challenge to health professionals on a global scale. Indeed, on the basis of the 2015 World Health Organization database for the European region, and calculating age-standardized mortality rates with the new European Standard population, CVD remains the most common cause of death among Europeans, accounting for 40% in males and 49% in females, and equating to >4 million deaths per year.[1] While mortality from CHD and stroke have decreased overall across Europe over the past decade, CHD continues to represent the single most common cause of death.[1] Importantly, morbidity data reveal that population-based rates of hospitalization for both CVD and stroke have increased; considered together with ever increasing rates of cardiovascular interventions, greater use of medications, and expanding needs for rehabilitation for disabilities, these overwhelming socioeconomic costs present a major burden to healthcare systems across Europe.[1]

How can we address this insurmountable challenge? Clearly lifestyle and diet represent our first line of action as currently recommended in recent guidelines,[2,3] and early identification and management of modifiable risk factors is paramount. Indeed, Avanzini et al.[4] have recently demonstrated that application of a comprehensive personalized preventive strategy in >12 000 high-risk subjects in general practice, but with suboptimal baseline risk factor control, led to gradual and significant improvement in global cardiovascular risk profile over a 5-year period. Thus, improvement in risk factor profile in the first year (including physical inactivity, hypertension, hypercholesterolaemia, diabetes, and an unhealthy diet) was independently and significantly associated with lower rates of cardiovascular events in subsequent years. These findings are entirely consistent with new observations from the EPIC-Norfolk prospective population study, in which even small improvement in modifiable risk factors led to substantial reduction in cardiovascular events.[5] These important findings indicate not only that an integrated approach to modifiable risk factor control is feasible, but equally that it is achievable in general practice. Finally, imaging technologies for detection of subclinical atherosclerosis may be invaluable in adding incremental value to strategies for diagnosis, risk stratification, and early initiation of prevention (see below).

The year 2015 is—and continues to be—a vintage one for seminal progress in our knowledge of the pathophysiology underlying acute coronary syndromes (ACSs), and of the epidemiology, diagnosis, and prognosis of CVD, thereby reflecting concerted efforts in our quest to prevent the global scourge of atherosclerotic vascular disease and its thrombotic complications. Such advances have been paralleled by the successful and rapid development of highly efficacious, innovative therapeutics to markedly lower circulating levels of LDL-C. Indeed, in the landmark INTERHEART study of risk factors for the first myocardial infarction across 52 countries worldwide, atherogenic cholesterol transported as LDL predominated, accounting for the majority of population-attributable risk.[6] In this context, it is especially relevant that recent genetic findings, involving Mendelian randomization strategies which integrate lifelong and therefore cumulative risk exposure, have consolidated the evidence base for a causal role of LDL in the pathophysiology of atherosclerosis and CVD[7–9] (Table 1). Moreover, the IMPROVE-IT trial[10] has now demonstrated that a mechanism of LDL lowering distinct from that of statins translates into clinical benefit. Ezetimibe-mediated inhibition of intestinal cholesterol absorption yielded incremental lowering of LDL-C on a background of statin treatment in this trial (involving 18 144 patients hospitalized for an ACS over 7 years) and translated into moderate improvement in cardiovascular outcomes, i.e. a 7.2% lower rate of major vascular events. Baseline levels of LDL-C were low (1.8 mmol/L or 70 mg/dL), with a 24% further reduction when ezetimibe was added to simvastatin; that cardiovascular benefit is proportional to the degree of LDL-C reduction is of critical relevance in this context.[11] Cardiovascular mortality was not modified, a finding which may result from several factors, and particularly the need for post-trial, long-term follow-up data on clinical benefit. Indeed, it is increasingly evident that such follow-up reveals legacy benefits of LDL lowering beyond the active intervention period in randomized, placebo-controlled statin trials, typically featuring decrease in cardiovascular death rates.[12] Clearly then, a new paradigm is appearing in which LDL lowering therapies may alter the pathophysiological course of atherosclerotic vascular disease and its thrombotic complications, potentially by inducing lesion stabilization, or lesion regression, or both.

In this condensed distillate of advances in prevention of CVD over the past year, three key areas stand out. First, the evolution from emphasis on the ruptured, vulnerable coronary plaque to coronary plaque erosion in the context of ACS, with immediate relevance to approaches searching for 'vulnerable' plaques.[13] Second, the appearance of advanced molecular methodologies for identification of biomarkers with potential for high predictive value.[14] Third, the advanced development, based on the molecular genetics of familial traits for cholesterol dysmetabolism associated with premature atherosclerosis, of monoclonal antibodies targeted to PCSK9 for marked reduction in LDL-C levels.[15] Importantly, progress in all three areas holds great promise to positively impact the care pathway for patients at high risk of CVD.