Hypertension is a complex disease, in which elevated blood pressure reflects the impairment of several regulatory and contraregulatory mechanisms and systems. This, in turn, may lead to development and progression of asymptomatic subclinical organ damage, hence promoting cardiovascular and renal diseases.
During the long natural history of hypertensive disease, the presence of hypertension-related organ damage at cardiac, vascular and renal level has been demonstrated to largely and substantially impact prognosis in terms of increased incidence of cardiovascular and renal outcomes in large clinical trials. In turn, evidence derived from relatively smaller clinical studies or predefined analyses from randomized clinical trials have demonstrated that prevention, delayed progression or even regression of organ damage during chronic antihypertensive therapy may translate into significant cardiovascular benefits.
A paradigmatic example, is provided by the Losartan Intervention For Endpoint reduction in hypertension trial in which the presence of left ventricular hypertrophy (LVH) or microalbuminuria (MAU) or both at baseline was associated with a significant increased risk of developing the primary composite endpoint (myocardial infarction, stroke and cardiovascular mortality) and mostly stroke during the follow-up [1,2]. This increased risk was also largely independent of how organ damage was assessed (electrocardiographic-LVH criteria with or without ST-segment strain or echocardiographic criteria for LVH) and it was not strictly related to the concomitant treatments or blood pressure changes during the study. In the same study, regression of LVH [3,4] or MAU  was paralleled by a progressive, persistent and significant reduction of the risk of cardiovascular outcomes. Other studies have linked regression of LVH to cardiovascular benefits in hypertension [6–9].
Given the importance of the presence and, mostly, of the development of hypertension-related organ damage in the clinical management of hypertension, it is quite disappointing that no major attempt has yet been made to consider markers of hypertension-related organ damage in modern tools and charts for cardiovascular risk assessment and evaluation developed and adopted in the US (Framingham Score) or European  countries. The only risk algorithm that has systematically taken into consideration the presence/absence of organ damage in the definition of estimated added cardiovascular risk is represented by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines [11,12].
Inclusion of markers of organ damage to risk charts or calculators is feasible and can be done at low cost, especially when the least expensive parameters (electrocardiographic-LVH, MAU, estimated glomerular filtration rate) are used. This may translate in improved cardiovascular risk stratification and more precise prognosis especially in intermediate-to-high risk patients. So, it is probably time to take advantage from this and focus more on these intermediate disease markers in risk charts applied to hypertensives.
In this latter regard, Sehestedt et al.  in a previous study were able to demonstrate that in an apparently healthy population, subclinical organ damages, as well as the number of abnormal parameters indicating subclinical organ damage, were associated with increased cardiovascular risk, independently of Systematic COronary Risk Evaluation (SCORE). Combining the risk models of SCORE and subclinical organ damage yielded greater performance on risk stratification and derived recommendations for primary prevention. This approach allows reclassification of the cardiovascular risk as defined by SCORE by simply adding LVH and MAU. For example, in patients with a SCORE of 5% or more, the cardiovascular risk would be doubled when taking into account the presence of any of these two markers of organ damage. At the same time, in patients with a SCORE less than 5%, the presence of LVH almost doubles the cardiovascular risk, whereas the presence of MAU increases cardiovascular risk by more than three-fold compared with those without MAU. This was consistent with former Italian studies showing that identification of subclinical organ damage reclassify the risk profile of hypertensive patients .
A new analysis performed by the same group , which is published in this issue of the Journal, assessed the predictive value of other markers of organ damage, such as urine albumin creatinine ratio (UACR), pulse wave velocity (PWV) and left ventricular mass index (LVMi), beyond traditional risk factors. The main findings of this new analysis may have particular relevance for the daily clinical practice of patients at cardiovascular risk because it further emphasizes the importance of integrating information from assessment of organ damage into risk charts calculators or algorithms.
Otherwise healthy individuals were, in fact, categorized according to SCORE , ESH/ESC  and Framingham risk score, and the analysis considered three major endpoints: cardiovascular death (SCORE-endpoint), a composite of cardiovascular death and nonfatal myocardial infarction and stroke (ESH/ESC-endpoint) and a composite endpoint of hospital admissions for ischemic heart disease, heart failure, peripheral arterial disease and transient cerebral ischemic attack (Framingham-endpoint).
For different levels of risk, the impact of organ damage is heterogeneous. In fact, practically no low risk individuals had a value of UACR, PWV or LVMi above the normal threshold and required risk reclassification, independently of the risk algorithm applied (SCORE, ESH/ESC or Framingham risk scores). On the contrary, although the majority (73–84%) of high-risk individuals according to the SCORE risk chart had values of UACR, PWV and LVMi below normal threshold indicating a risk allocation into a lower risk category, the observed 10-year risk of cardiovascular death (SCORE)  in these individuals was not below the required 5% for risk reclassification. Thus, these individuals remained at high risk. At the same time, marginal proportions of high-risk individuals according to the ESH/ESC and Framingham risk charts were reclassified into lower risk according to the observed risk (8 and 12%, respectively); as a consequence, the majority of these individuals remained at high risk. With a different evidence-based approach, we have most recently provided support to the concept that electrocardiographic-LVH and MAU permit reclassification of patients with hypertension stratified with the SCORE approach . We believe that it is now time to shoot beyond the risk classification, traditionally, based on conventional cardiovascular risk factors. Clinical practice provides today an amount of additional information that doctors can easily apply to patients’ risk stratification.
Combined risk models and subclinical organ damage have major impact on risk stratification and, mostly, on risk reclassification. They may indeed significantly impact on a pragmatic risk evaluation, particularly in those patients at intermediate risk in which proper assessment of cardiovascular risk and organ damage may improve clinical management and, thus, eventually impact on long-term outcomes.
Conflicts of interest
There are no conflicts of interest and no financial disclosures to make.
1. Ibsen H, Wachtell K, Olsen MH, Borch-Johnsen K, Lindholm LH, Mogensen CE, et al. Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy. J Hypertens
2. Kjeldsen SE, Devereux RB, Hille DA, Lyle PA, Dahlof B, Julius S, et al. Predictors of cardiovascular events in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention for Endpoint reduction in hypertension study. Blood Press
3. Okin PM, Devereux RB, Jern S, Kjeldsen SE, Julius S, Nieminen MS, et al. Regression of electrocardiographic left ventricular hypertrophy by losartan versus atenolol: the Losartan Intervention for Endpoint reduction in Hypertension (LIFE) Study. Circulation
4. Devereux RB, Dahlof B, Gerdts E, Boman K, Nieminen MS, Papademetriou V, et al. Regression of hypertensive left ventricular hypertrophy by losartan compared with atenolol: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial. Circulation
5. Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, Mogensen CE, et al. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study. Hypertension
6. Verdecchia P, Sleight P, Mancia G, Fagard R, Trimarco B, Schmieder RE, et al. Effects of telmisartan, ramipril, and their combination on left ventricular hypertrophy in individuals at high vascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease. Circulation
7. Verdecchia P, Angeli F, Gattobigio R, Sardone M, Pede S, Reboldi GP. Regression of left ventricular hypertrophy and prevention of stroke in hypertensive subjects. Am J Hypertens
8. Rosei EA, Muiesan ML. Early target organ damage and its reversibility: the heart. Clin Exp Hypertens
2004; 26 (7–8):673–687.
9. Muiesan ML, Salvetti M, Monteduro C, Bonzi B, Paini A, Viola S, et al. Left ventricular concentric geometry during treatment adversely affects cardiovascular prognosis in hypertensive patients. Hypertension
10. Conroy RM, Pyorala K, Fitzgerald AP, Sans S, Menotti A, De Backer G, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J
11. Volpe M. Similarities and differences in hypertension guidelines: the need for one roadmap to lower cardiovascular risk. High Blood Press Cardiovasc Prev
12. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. The task force for the management of arterial hypertension of the European Society of H, The task force for the management of arterial hypertension of the European Society of C. 2007 Guidelines 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
13. Sehestedt T, Jeppesen J, Hansen TW, Wachtell K, Ibsen H, Torp-Pedersen C, et al. Risk prediction is improved by adding markers of subclinical organ damage to SCORE. Eur Heart J
14. Cuspidi C, Ambrosioni E, Mancia G, Pessina AC, Trimarco B, Zanchetti A. Role of echocardiography and carotid ultrasonography in stratifying risk in patients with essential hypertension: the Assessment of Prognostic Risk Observational Survey. J Hypertens
15. Sehestedt T, Jeppesen J, Hansen TW, Rasmussen S, Wachtell K, Ibsen H, et al
. Thresholds for pulse wave velocity, urine albumin creatinine ratio and left ventricular mass index using SCORE, Framingham and ESH/ESC risk charts. J Hypertens
16. Volpe M, Battistoni A, Tocci G, Rosei EA, Catapano AL, Coppo R, et al. Cardiovascular risk assessment beyond Systemic Coronary Risk Estimation: a role for organ damage markers. J Hypertens