Danno d organo bersaglio e rischio CV. Persiste un ruolo prognostico oltre la patologia d organo?

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1 Danno d organo bersaglio e rischio CV. Persiste un ruolo prognostico oltre la patologia d organo? Prof. Massimo Salvetti Clinica Medica University of Brescia

2 Percieved risk

3 Actual risk

4 Sehestedt et al, European Heart Journal 2010 Risk prediction is improved by adding markers of sublinical organ damage to SCORE

5 Stratification of total CV risk Further emphasis has been given to identification of organ damage, since hypertension-related asymptomatic alterations in several organs indicate progression in the CVD continuum, which markedly increases the risk beyond that caused by the simple presence of risk factors 2013 ESH/ESC Guidelines for the management of arterial hypertension

6 Evaluation of the elderly patient with known or suspected hypertension must accurately determine BP, and if elevated: 1) identify reversible and/or treatable causes; 2) evaluate for organ damage; 3) assess for other CVD risk factors/comorbid conditions affecting prognosis; and 4) identify barriers to treatment adherence. JACC 2014

7 Journal of Hypertension 2010 * p< Low * Moderate * * High * Routine + echocardiography + renal TOD + PWV + carotid ultrasound

8 Factors - other than office BP - influencing prognosis used for stratification of total CV risk (2) 2013 ESH/ESC Guidelines for the management of arterial hypertension

9 Search for asymptomatic organ damage - Kidney 2013 ESH/ESC Guidelines for the management of arterial hypertension

10 (incidence rate ratio) Hunt II Study, Arch Intern Med participants of the second Nord-Trøndelag Health Study (HUNT II), a Norwegian community-based health study, followed for 8.3 years with a 71% participation rate Cardiovascular mortality risk

11 The combined variable improved cardiovascular risk stratification at all age levels, but particularly in elderly persons where the predictive power of traditional risk factors is attenuated... Arch Intern Med. 2007

12 European Heart Journal 2007 Prospective study of 70-year-old men free from HF at baseline (Uppsala Longitudinal Study of Adult Men coho Cutoff: UAER median value, 4.7 mg/min In Cox proportional hazards models adjusted for established and novel risk factors for HF, a 1 SD increase in log UAER increased the risk of HF in individuals without anti hypertensive treatment (hazard ratio 1.49; 95% CI ; p < 0.005)

13 Search for asymptomatic organ damage - Arteries 2013 ESH/ESC Guidelines for the management of arterial hypertension

14 A man is as old as his arteries Thomas Sydenham,

15 Mannheim Carotid Intima-Media Thickness Consensus Update ( ) Cerebrovascular Disease 2007; ;23:75 80 plaque and IMT measurement according to Mannheim consensus. 1: thickness > 1.5 mm 2: lumen encroaching > 0.5 mm; 3, 4: > 50% of the surrounding IMT value

16 Unadjusted Cumulative Event-free Rates for the Combined End Point of Myocardial Infarction or Stroke, According to Quintile of Combined Intima-Media Thickness 5858 subjects 65 years of age or older, follow-up period of 6.2 years NEJM 1999, D.H. O Leary et al.

17 1289 men aged 60 to 74 years without a previous stroke or CHD Incidence of stroke Men with a plaque in the ICA had a 3-fold higher risk of stroke than those without The combination a plaque, of CCA and internal the carotid plaque artery (ICA) surface wall thickness irregularity was a further better predictor of the risk of stroke than was CCA wall thickness alone. increased the stroke risk. A significant excess risk of stroke was confined to men with an uncalcified plaque. Stroke 2004

18 DBP (mm Hg) DBP (mm Hg) SBP (mm Hg) SBP (mm Hg) DBP (mm Hg) DBP (mm Hg) SBP (mm Hg) SBP (mm Hg) Mean Systolic and Diastolic BP by Age and Race/Ethnicity for Men and Women (US Population ³Age 18 Years, NHANES III) Non-Hispanic Black Non-Hispanic White Mexican American Pulse pressure 110 Pulse pressure Men, Age (y) Women, Age (y) Burt VI, et al. Hypertension. 1995;25:

19 Compliance function of large arteries Arterial compliance Arterial compliance Left Ventricl e Peripheral resistances Left Ventricl e Peripheral resistances SYSTOLE DIASTOLE

20 Compliance function of large arteries Arterial compliance Arterial compliance Left Ventricl e Peripheral resistances Left Ventricl e Peripheral resistances SYSTOLE DIASTOLE

21 Carotid-femoral pulse wave velocity DL dp PWV. Dt. V dv Dt L Carotid femoral PWV can be assimilated to aortic stiffness

22 Reference values for pulse wave velocity (PWV): mean values according to age and blood pressure categories ( subjects) Reference Values for Arterial Stiffness' Collaboration. Eur Heart J 2010;31:

23 A cohort of 141 subjects (mean age, 87.1±6.6 years), dementia in 63.8 %, was studied in 3 geriatrics departments in a Paris suburb. During the 30-month follow-up, 56 patients died (27 from CV events). Logistic regressions indicated that age (p=0.005) and a loss of autonomy (p=0.01) were the best predictors of overall mortality. For cardiovascular mortality, aortic PWV was the major risk predictor (P0.016). Arterioscler Thromb Vasc Biol. 2001

24 Reclassification indices showed that the addition of apwv improved risk prediction (13% for 10-year CVD risk for intermediate risk). Ben Shlomo B et al, JACC 2014

25 Ben Shlomo et al, JACC 2014

26 280 eighty older subjects with subjective complaints of memory loss and no previous stroke (age 78.3±6.3 yrs) Interpretation: Systemic hemodynamic parameters (higher PWV and hypotension) together with cerebral microvascular damage (WML) are significantly associated with poorer cognitive function and may identify older subjects with subjective complaints of memory loss at higher risk of cognitive decline. International Journal of Cardiology 2013

27 Hypertension 2013; 61:

28 Hypertension 2014

29 Correlation between PWV and LV structure Studio Vobarno, Clinica Medica, Università di Brescia

30

31 Search for asymptomatic organ damage - Heart 2013 ESH/ESC Guidelines for the management of arterial hypertension

32 Increase in wall thickness with age in healthy men and women Bronx Longitudinal Study Aging Prevalence of concentric LV geometry increases with agenormalized RWT Values age-normalized RWTm = 0.41 RWTp = 0.40 Gerstenblith G et al. Circulation. 1977;56: de Simone G et al Hypertension. 2005;45:64-68

33 Prevalenza Disfunzione Diastolica (Criteri Primari) 60 % 50 p < p = p = p = p < Tutti M F C NC No Sì Controllo PA Sindrome Metabolica > > > 80 < Età PAS Zanchetti et al., J Hypertens 2007; 25:

34 LVH and CV Risk in Different Populations LVH diagnosed by echocardiography is a powerful predictor of myocardial infarction, stroke and CV death in: Apparently uncomplicated hypertensive patients In subjects with or without angiographic coronary heart disease In patients with previous myocardial infarction In subjects from general populations in epidemiological studies It has been estimated that 1g/m2 increase in LVMI is associated with a 1-2 % increase in the risk of CV events

35 Myocytes Cardiomyocite changes Hypertrophy Cell loss (apoptosis) Functional changes Systolic Dysfunction Pressure Overload Extracellular matrix Collagen network changes Reactive fibrosis Replacement fibrosis HF 26/01/ :09:55 Vascular Compartment Coronary disease Microcirculation changes Capillary rarefaction Diastolic Dysfunction

36 LV mass and incident heart failure The Cardiovascular Health Study Quartiles of echocardiographic LVM/BSA (g/m2): < 67.7, 67.8 to 79.2, 79.3 to 93.5, and > Drazner et al. JACC 2004; 43 :

37 In multivariable logistic regression models, including age, sex, BP levels, and use of antihypertensive drugs as covariates, the highest LVMI was found to be independently associated with a two-fold higher likelihood of having dementia. The association persisted significant even after adjustment for arterial stiffness

38 Sensitivity to detect treatment-induced changes, time to change and prognostic value of change by markers of asymptomatic OD 2013 ESH/ESC Guidelines for the management of arterial hypertension

39 VOBARNO Study 478 subjects (age range years) 40% elderly (193 subjects) % Prevalence of hypertension 53 Non elderly Χ 2 < Elderly Clinica Medica, University of Brescia % % Uncontrolled hypertension Χ 2 < Non elderly Elderly Resistant hypertension Χ 2 < Non elderly Elderly

40 Prevalence of OD 35 Prevalence of LVH % , ,1 Non elderly Elderly Studio Vobarno, Clinica Medica, Università di Brescia

41 Prevalence of OD Prevalence of IMT or plaques Prevalence of PWV>10 m/s % ,2 Non elderly 95,9 Elderly % ,1 Non elderly 68,5 Elderly Studio Vobarno, Clinica Medica, Università di Brescia

42 Grazie per l attenzione

43

44 8.4: Continued search for asymptomatic organ damage On the whole, it appears reasonable to search for at least some asymptomatic OD, not only for the initial stratification of CV risk, but also during follow-up 2013 ESH/ESC Guidelines for the management of arterial hypertension

45 0 BB VS OTHER DRUGS 31 paired comparisons 2680 pts 0 ARB VS OTHER DRUGS 20 paired comparisons 2384 pts BB -8,8 Other drugs * -11, * -12,6-9,4 ARB Other drugs * p<0.01 Pairwise Comparison of Each Drug Class With the Other Classes Statistically Combined Fagard et al, Hypertension 2009

46 Treatment Age Years Treatment Duration N pts Change in LVM % Change in SBP mmhg Terpstra W et al 2000 ELVERA Lisinopril years % -26 Amlodipine % Schulman S et al 1990 Verapamil > 60 years 6 months % -28 atenolol % -32 Dahlof et al 2004 LIFE Losartan years 6 months % -30 Mean age Atenolol % yrs

47 Comparative effect of antihypertensive drugs on aortic stiffness, wave reflection and central PP Aortic PWV Central PP, Augmentation index ACE-Inhibitors Angiotensin Receptor Blockers Calcium channel blockers Thiazide diuretics Vasodilating β-blockers Non vasodilating β-blockers

48 22 trials published between 1996 and 2005: - 8 trials antihypertensive drugs vs placebo or no-treatment - 9 trials new with old drug classes - 5 trials ACE inhibitors and CCBs Conclusions: Calcium channel blockers reduce carotid intima-media thickening. This mechanism might contribute to their superior protection against stroke. Stroke online June 8, 2006

49

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