Prevention: some important steps forward, but many unmet needs in a world with cardiovascular disease as the leading cause of death

Prevention is better than cure: the proverb remains as important as is has been for decades and centuries. Without a doubt, we have made substantial progress: we can lower blood pressure, if it is too high,1 we can treat hyperlipidaemia as again outlined in the 2016 ESC Guidelines,2 and indeed for the first time we can prevent cardiovascular mortality in diabetics3—nevertheless, we do not do enough, It is of note that many patients with high blood pressure do not reach recommended targets, many patients with hyperlipidaemia are inadequately treated or stop drugs when negative media reports appear,4 and diabetics are often far from being well controlled. Thus, the ‘Epidemiological update 2016 for cardiovascular disease in Europe,5 by Nick Townsend and colleagues from the British Heart Foundation Centre on Population Approaches for Non-Communicable Disease Prevention in Oxford, UK comes at the right time to remind us of the unmet needs in cardiovascular medicine. Of note, the current report is the fourth in a series of papers describing the burden of cardiovascular disease within Europe. Not surprisingly, as the implementation of preventive measures is still less than perfect, cardiovascular disease remains the most common cause of death worldwide, with the 2013 Global Burden of Disease study estimating that cardiovascular disease caused 17.3 million deaths globally. It accounted for 31.5% of all deaths and 45% of all non-communicable disease deaths, more than twice that caused by cancer, as well as more than all communicable, maternal, neonatal, and nutritional disorders combined. The 2013 Global Burden of Disease study also reported that cardiovascular disease caused a greater number of deaths and was responsible for a greater percentage of all deaths than in 1990 when 12.3 million deaths were attributed to cardiovascular disease, corresponding to 25.9% of total deaths. Previous publications in this series have reported that despite the decreases in cardiovascular disease mortality in Europe, >4 million people die from cardiovascular disease across the continent every year, with >1.4 million dying prematurely, before the age of 75 years. In their report, the authors present an updated overview of the burden of cardiovascular disease in Europe, including new statistics for mortality, morbidity, and treatment. Where possible, statistics are provided for all cardiovascular disease, and for coronary heart disease and stroke in particular. All data included here are updated from previous publications; the authors present prevalence statistics for the first time. This series of publications describing the current burden and distribution of cardiovascular disease and coronary heart disease in Europe has been based on the European Cardiovascular Disease Statistics 2012 report, the fourth in a series of Europe-wide compendia, which was published jointly by the European Heart Network and the European Society of Cardiology. (A) Nomogram including independent prognostic factors. (B) To obtain nomogram-predicted probability of unfavourable outcome, locate the patient values at each axis. Subsequently, draw a vertical line to the ‘Point’ axis to determine how many points are attributed for each variable value. Then sum the points for all variables. Locate the sum on the ‘Total Points’ line to assess the individual probability of unfavourable outcome. For instance, we obtain 22 points for a 30-year-old patient, 25 points if the cardiac arrest occurred at home, 27 points if it was a nonshockable rhythm, 14 points for 5 min of ‘no flow’, 8 points for 10 min of ‘low flow’, 43 point for 3 mg of epinephrine, and 38 points if the pH was 7.10 at admission. The total score for this sample patient is therefore 22 + 25 + 27 + 14 + 8 + 43 + 38 = 177 points. By drawing a vertical line crossing the ‘risk of poor outcome’ line, it indicates 88% for probability of a bad outcome. BLS, basic life support; ROSC, return of spontaneous circulation. (from Maupain C, Bougouin W, Lamhaut L, Deye N, Diehl J-L,Geri G, Perier M-C, Beganton F, Marijon E, Jouven X, Cariou A, Dumas F. The CAHP (Cardiac Arrest Hospital Prognosis) score: a tool for risk stratification after out-of-hospital cardiac arrest. See pages 3222–3228.) The contribution by Marx et al. is accompanied by a insightful Editorial entitled ‘Sodium–glucose co-transporter-2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus: the road ahead’, authored by Bernard Zinman from the Mount Sinai Health System in Toronto, Canada.10 Another important issue in prevention is stroke prevention, not only in patients with hypertension, but also particularly in those with atrial fibrillation. To that end, vitamin K antagonists and the novel oral anticoagulants are used.11,12 To balance stroke protection and bleeding risk, better stroke risk prediction is needed. The ATRIA stroke risk score was developed and validated in two large California community atrial fibrillation cohorts. In a first clinical research paper entitled ‘Comparison of the ATRIA, CHADS2, and CHA2DS2-VASc stroke risk scores in predicting ischaemic stroke in a large Swedish cohort of patients with atrial fibrillation’, Sara Aspberg and colleagues from the Karolinska Institutet in Stockholm, Sweden compared the performance of the ATRIA, CHADS2, and CHA2DS2-VASc scores, the latter of which is recommended by current ESC Guidelines,13 in a national Swedish atrial fibrillation cohort.14 The authors examined all 152 153 Swedish patients hospitalized, or visiting a hospital-based outpatient clinic, with a diagnosis of atrial fibrillation over a 5-year period not receiving warfarin. Overall, 11 053 acute ischaemic strokes were observed, with a mean rate 3.2% per year, higher than the 2% per year observed in the California cohorts. Using entire point scores, ATRIA had a good C-index of 0.708, significantly better than CHADS2 which received 0.69, or CHA2DS2-VASc with 0.694. Using published cut-off points for low, moderate, or high risk, the C-indiex deteriorated, but the ATRIA score remained superior. The net reclassification improvement or NRI favoured ATRIA, with a value of 0.16 vs. CHADS2, and of 0.21 vs. CHA2DS2-VASc. The NRI decreased when cut-off points were altered to better fit the cohort’s stroke rates. The authors conclude that the ATRIA score predicted ischaemic stroke risk better than CHADS2 or CHA2DS2-VASc. However, relative performance of the categorical scores varied by population stroke rates. Score cut-off points may need to be optimized to better fit local population stroke rates. These provocative findings are further discussed in a comprehensive Editorial authored by John A. Cairns from McMaster University Medical Centre in Ontario, Canada.15 Abdominal aortic aneurysms are often accidental findings, particularly in elderly smokers. Depending on size, surgery or stenting might be indicated. Thus, in patients with smaller aneurysms, inhibition of their growth might represent an important preventive measure. In a randomized placebo-controlled trial ‘An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomized placebo-controlled trial (AARDVARK)’, Colin David Bicknell and co-investigators of the Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK trial investigated whether ACE inhibition reduces the growth rate of small abdominal aortic aneurysms, independent of blood pressure lowering.16 This three-arm, multicentre, single-blind, randomized controlled trial was conducted in 14 hospitals in England in 224 subjects 55 years or older, with abdominal aortic aneurysms of diameter 3.0–5.4 cm. They were randomized 1:1:1 to receive perindopril arginine 10 mg, amlodipine 5 mg, or placebo over 2 years. Mean changes in systolic blood pressure in the three groups averaged 0.5 mmHg, –9.5 mmHg, and –6.7mmHg, respectively. No significant differences in the modelled annual growth rates were apparent. The estimated difference in annual growth between the perindopril and placebo groups was 0.08 mm. Similar numbers of aneurysms in each group reached 5.5 cm diameter and/or underwent elective surgery. Thus, the authors conclude that the growth rates of small abdominal aortic aneurysms are lower than anticipated, but neither perindopril nor amlodipine was effective in lowering their growth rate. Survival after out-of-hospital cardiac arrest remains disappointingly low. Among patients admitted alive, early prognostication remains challenging. In a third clinical research paper entitled ‘The CAHP (Cardiac Arrest Hospital Prognosis) score: a tool for risk stratification after out-of-hospital cardiac arrest’, Florence Dumas et al. from the Paris Descartes University in France developed from the Sudden Death Expertise Center registry in Paris a stratification score for patients admitted to an intensive care unit after out-of-hospital cardiac arrest, according to their neurological outcome.17 The primary outcome was poor neurological outcome defined as Cerebral Performance Category 3, 4, or 5 at hospital discharge. The score was validated in both a prospective and an external data set, in the Parisian Cardiac Arrest Registry. The developmental data set included 819 patients. Seven variables were independently associated with poor neurological outcome, i.e. age, non-shockable rhythm, time from collapse to basic life support, time from basic life support to return of spontaneous circulation, location of cardiac arrest, epinephrine dose, and arterial pH. Three risks groups were identified: low risk (score ≤150, 39% unfavourable outcome), medium risk (score 150–200, 81% unfavourable outcome), and high-risk group (score ≥200, 100% unfavorable outcome). The area under the curve (AUC) of the score was 0.93 and the discrimination value in the validation data sets was consistent. The authors conclude that the Cardiac Arrest Hospital Prognosis score represents a simple tool for early stratification of patients admitted to an intensive care unit after out-of-hospital cardiac arrest. A high-risk category of patients with very poor prognosis can be easily identified. The findings are further discussed in an interesting Editorial by Kjetil Sunde from the Oslo University Hospital in Norway.18 The editors hope that this issue of the European Heart Journal will be of interest to its readers.