2017 has been a prolific year for high-impact publications in this discipline. In the field of nutrition, the clinical practice guidelines recommend replacing the intake of fats, especially saturated fats, with unsaturated fats and carbohydrates to avoid increasing low-density lipoprotein cholesterol (LDL-C) and consequently the occurrence of cardiovascular (CV) events. Recent randomized clinical trials and metanalyses of observational studies contradict these recommendations. One such study is the PURE1 cohort study, with 135 335 individuals from 18 countries, in which it was observed that a high intake of carbohydrates (> 60%) increased the risk of total mortality, whereas intake of fats (including saturated fats) reduced this risk, with no association found between total fat intake and CV disease or CV mortality, and there was even an inversely proportional relationship between saturated fats and stroke. It is without doubt a study that raises new questions and will require, at least, revision of the current recommendations on the appropriate dietary proportion of the different macronutrients.
Regarding lipids, the Fourier2 trial has been the real protagonist and has provided data on the CV benefits of treatment with evolocumab. In this trial, 27 567 patients with atherosclerotic disease (acute myocardial infarction, nonhemorrhagic stroke, or symptomatic peripheral arterial disease) and with LDL-C > 70 mg/dL (or non—high-density lipoprotein cholesterol > 100mg/dL) were randomized to receive evolocumab 140mg or placebo every 2 weeks. LDL-C decreased by 59% in the evolocumab group and reached a mean of 30mg/dL. The reduction in relative risk for the primary outcome (CV death, acute myocardial infarct or stroke) in the evolocumab group was 15% at 36 months, with the greatest benefit occurring after the first 12 months. There were no significant differences regarding serious side effects. This study demonstrated that inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) with evolocumab reduces LDL-C and translates to CV benefits.
For diabetes, the most noteworthy study was the CANVAS3 trial, in which 10 142 diabetic patients with high CV risk were randomized to receive canagliflozin or placebo. The canagliflozin group achieved a 14% reduction in the primary outcome (composite outcome of CV mortality, nonfatal myocardial infarction and nonfatal stroke), 26.9 vs 31.5 events/1000 patients/year (hazard ratio [HR] = 0.86; 95% confidence interval [95%CI], 0.75-0.97; P = .02 for superiority). There was an increase of almost double the number of amputations in the treated group (6.3 vs 3.4/1000 patients/year; HR = 1.97). This study provides evidence that the CV benefits of SGLT2 inhibitor oral antidiabetics are a class effect. It also supports the focus of treatment of diabetes being based not only on lowering glucose levels, but also on more general effects in an aim to reduce CV events and improve prognosis, similar to what was seen last year with the GLP1 agonists liraglutide and semaglutide.
Another publication was the first study to demonstrate that a CV screening program can be associated with a reduction in mortality. The Viborg Vascular4 (VIVA) trial is a prospective randomized trial conducted in 50 156 Danish men aged between 65 and 74 years, assigned to triple screening for abdominal aortic aneurysm (AAA), peripheral vascular disease (PAD), and hypertension versus standard care. Those diagnosed with PAD or AAA received smoking cessation therapy, aspirin (75mg/day), simvastatin (40mg/day) and an antihypertensive, and those with AAA > 50 mm were referred to vascular surgery. More than 20% of participants received a diagnosis: 3% with AAA, 11% with PAD, and 11% with untreated hypertension. There was a 7% reduction in 5-year mortality, and 1 life was saved for every 169 participants assessed, making it more cost-effective than the European cancer screening programs. A substudy of the VIVA trial5 also showed an inverse association between AAA growth and glycated hemoglobin concentration in individuals with and without known diabetes.
The inflammatory hypothesis of atherothrombotic disease is based on inflammation playing a role in the formation, progression and rupture of the atheromatous plaque and in the generation of acute coronary events. Canakinumab is a monoclonal antibody against interleukin 1β that produces an anti-inflammatory effect. The CANTOS trial6 compared subcutaneous 3-monthly administration of canakinumab vs placebo in patients with a history of acute myocardial infarction and high levels of C-reactive protein, with a combined primary outcome of CV death, nonfatal acute myocardial infarction, and nonfatal stroke at 48 months.
The main results were a significant reduction in the primary outcome in the treatment group due to a reduction in nonfatal acute myocardial infarction. There was also a reduction in C-reactive protein levels, no differences in LDL-C levels, and a lower risk of cancer in the canakinumab group vs placebo group, although this was at the expense of an increase in fatal infections. The most relevant result of this study was that it demonstrated the inflammation theory, paving the way in the search for promising new lines of treatment.
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