Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/IdiPAZ – CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Correspondence to José R. Banegas, MD, Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo 2, 28029 Madrid, Spain. Tel: +34 91 497 5425; fax: +34 91 497 5353; e-mail: firstname.lastname@example.org
Assessment of cardiovascular disease (CVD) risk based on a single risk factor can be misleading, and hypertension is not an exception. Because hypertension usually clusters with other major risk factors, the physician should routinely screen for the presence of these other factors. A global approach in evaluating the risk factors provides the best opportunity to identify individuals at risk for CVD over a time interval that usually ranges from a few years to a decade [1,2]. Age, sex, SBP, smoking, total cholesterol, HDL-cholesterol, and diabetes mellitus are the factors commonly used to estimate the risk for a first coronary heart disease (CHD) event . There seems to be some consensus in the scientific community that hypertensive patients are more appropriately targeted for therapy by using CVD risk stratification, and that the main goal of the therapy is to reduce the absolute CVD risk [1,4,5].
A number of risk equations are available for various CVD outcomes associated with hypertension, to enable physicians to pool all the relevant risk factor information so as to arrive at a risk estimate [3,6–10]. One barrier in the use of CVD-risk equations is the multiplicity of outcomes considered by the different guidelines. On the basis of the experience of the Framingham Study, prediction algorithms used total CHD  or hard CHD (myocardial infarction or CHD death) , and more recently an inclusive definition of CVD encompassing the first occurrence of CHD, stroke, peripheral artery disease, and heart failure [3,6]. In addition, the Systematic Coronary Risk Estimation (SCORE) project developed 10-year cardiovascular mortality risk equations for European countries , which have been adopted by the 2012 European guidelines on CVD prevention . Other developments, such as the Prospective Cardiovascular Münster study in Germany used hard CHD , and the British National Institute for Health and Clinical Excellence guidelines support the cardiovascular disease risk score (QRISK), which includes CHD and stroke outcomes . Lastly, the 2013 European ESH/ESC guidelines on hypertension management have retained the SCORE risk prediction and classification system , and the American College of Cardiology/American Heart Association in the United States has recently proposed a composite of first occurrence of nonfatal myocardial infarction or CHD death, or fatal or nonfatal stroke over a 10-year period, for the assessment of CVD risk .
The work by Zambon et al. published in this issue of the Journal, is a flexible, parsimonious exercise of regression modeling in hypertension epidemiology, using a comprehensive set of trials of hypertension treatment to examine the relationship of CVD death with major or more inclusive CVD or all cause death. The main contribution of this article is that it provides a set of rates ratios of various outcomes to CVD death that may be used as multipliers to the CVD death risk calculated with SCORE system  to estimate the risk of other CVD outcomes with relevance for patients and physicians; and, unlike previous attempts , the risk of all-cause death can also be obtained. The latter estimate is also important, as all people eventually die regardless of the specific cause. This information can also be used the other way round, to translate Framingham-based-specific CVD risks into CVD death risk estimates. Interestingly, Zambon et al. found that for any category of CVD death risk, their results were quite the same regardless of age (<65 or ≥65 years) and preexisting CVD (results were robust to the exclusion of trials of secondary-prevention).
The work by Zambon et al. could be seen as adding noise to the already complex, inflated world of CVD-risk equations. Nevertheless, it could also be seen as a worthy attempt to provide the clinicians with an a la carte table for risk prediction/classification, helpful for users interested in individual CVD outcomes or even in total mortality. We should monitor whether this contribution will effectively serve to overcome some barriers to the use of CVD scoring systems in clinical practice .
The information on outcomes for risk assessment can come from either observational studies or trials. No doubt that trials-based outcomes are more accurate, but they are also limited by a shorter duration of follow-up. Even though 1000 patients-years in a trial can be expressed as 100 persons in 10 years under stable conditions, the fact remains that the duration of a trial is usually shorter than 5 years, potentially affecting the relation between outcomes. Also, the SCORE and the Framingham cohorts usually included individuals without blood pressure therapy, a condition less likely to be met in the recent trials of antihypertensive treatment. Nevertheless, when placebo-controlled trials were considered as reference, the ratio of CVD outcomes or all-cause death over CVD death remained quite similar to trials with active treatment as reference. A potential limitation of this study was that it did not consider that the proportional distribution of CVD outcomes varies with sex, and that separate multipliers may need to be obtained for men and women. Nevertheless, this would make more complex the use of the multipliers proposed by the authors. Once again, simplicity should predominate over precision in this science of risk assessment. Finally, the SCORE system had little representation of minority groups, which may limit the utility of the study by Zambon et al. outside of Europe.
Admittedly, CVD-risk assessment is worth using in clinical practice. However, this should be put into the context of the effectiveness of risk assessment, and the poor blood pressure control generally achieved in most populations and settings [14,15]. Although there is some evidence that preventive strategies based on CVD risk are more cost-effective than those based on individual-risk factors , there is insufficient evidence that they improve clinical practice (e.g. reducing hard events). In addition, those countries that have pursued more aggressively control of hypertension are those that have achieved better figures for hypertension control and stroke mortality [14,17]. Also, there are recent large-scale multifaceted initiatives that have achieved impressive improvement in blood pressure control rate in large population even without considering risk assessment .
The impact of guidelines on CVD treatment seems to be bigger than that from risk tools, at least for hypertension. In fact, guidelines usually tell the clinicians that practically every hypertensive patient has to be treated with blood pressure medication sooner or later, regardless of their CVD risk [4,5]. We think that at least in hypertension management, the utility of a risk tool should be mostly to illustrate and motivate the patient that prevention and control of CVD risk factors is worth doing. Future research should probably include the utility of short-term and long-term (lifetime) risk for motivating behavioral change and adherence to therapy [11,19].
Funding: This work has been partially funded by FIS grant PI13/02321, and Cátedra de la Universidad Autónoma de Madrid de Epidemiología y Control del Riesgo Cardiovascular, Madrid, Spain.
Conflicts of interest
There are no conflicts of interest.
1. Kannel WB. Hypertension: reflections on risks and prognostication. Med Clin North Am. 2009; 93:541–558.
2. Wilson PWF. Black HR, Elliott WJ. Prediction of global cardiovascular risk in hypertension. Hypertension. A companyon to Braunwald's Heart Disease. 2nd. edn. Philadelphia:Saunders; 2013;. 144–150.
3. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998; 97:1837–1847.
4. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012; 33:1635–1701.
5. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et al. 2013 ESH/ESCguidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013; 34:2159–2219.
6. D’Agostino RB Sr, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, Kannel WB. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008; 117:743–753.
7. Conroy RM, Pyorala K, Fitzgerald AP, Sans S, Menotti A, De Backer G. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003; 24:987–1003.
8. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection: Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel, III). JAMA. 2001; 285:2486–2497.
9. Assmann G, Cullen P, Schulte H. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Munster (PROCAM) study. Circulation. 2002; 105:310–315.
10. Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Minhas R, Sheikh A, et al. Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ. 2008; 336:1475–1482.
11. Goff DC Jr, Lloyd-Jones DM, Bennett G, O’Donnell CJ, Coady S, Robinson J, et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 10.1016/j.jacc.2013.11.005.
12. Zambon A, Arfè A, Corrao G, Zanchetti A. Relationships of different types of event to cardiovascular death in trials of antihypertensive treatment: an aid to definition of total cardiovascular disease risk in hypertension. J Hypertens. 2014; 32:495–508.
13. Dallongeville J, Banegas JR, Tubach F, Guallar E, Borghi C, De Backer G, et al. EURIKA Investigators Survey of physicians’ practices in the control of cardiovascular risk factors: the EURIKA study. Eur J Prev Cardiol. 2012; 19:541–550.
14. Wolf-Maier K, Cooper RS, Kramer H, Banegas JR, Giampaoli S, Joffres MR, et al. Hypertension treatment and control in five European countries, Canada, and the United States. Hypertension. 2004; 43:10–17.
15. Rodríguez-Artalejo F, Banegas JR. Cardiovascular risk in clinical decision making. Curr Hypertens Rep. 2007; 9:339–341.
16. Murray CJ, Lauer JA, Hutubessy RC, Niessen L, Tomijima N, Rodgers A, et al. Effectiveness and costs of interventions to lower systolic blood pressure and cholesterol: a global and regional analysis on reduction of cardiovascular-disease risk. Lancet. 2003; 361:717–725.
17. Wolf-Maier K, Cooper RS, Banegas JR, Giampaoli S, Hense HW, Joffres M, et al. Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States. JAMA. 2003; 289:2363–2369.
18. Jaffe MG, Lee GA, Young JD, Sidney S, Go AS. Improved blood pressure control associated with a large-scale hypertension program. JAMA. 2013; 310:699–705.
19. Lloyd-Jones DM, Leip EP, Larson MG, D’Agostino RB, Beiser A, Wilson PW, et al. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation. 2006; 113:791–798.