Risk Factors of chronic complex co-morbidities. Aldo Pietro Maggioni, MD ANMCO Research Center Firenze, Italy

Transcription

1 Risk Factors of chronic complex co-morbidities Aldo Pietro Maggioni, MD ANMCO Research Center Firenze, Italy

2 Statement 1 In real world practice (and in clinical trials), complex co-morbidities are the rule in patients with cardiovascular diseases

3 Stable CHD PEACE Trial:Baseline Medical History Characteristic, % Trandolapril Placebo Documented MI CABG or PCI Diabetes Hypertension Stroke or TIA 7 6

4 Recent postmi with LVSD/HF Medical History (%) Diabetes mellitus 23.1 Hypertension 55.2 Smoking 31.7 COPD 8.9 Prior: Myocardial infarction 27.9 Heart failure 14.8 Stroke 6.1 CABG 7.0 PCI 7.3 Baseline Medications (%): ACE inhibitor* 39.6 ARB* 1.2 Beta-blocker 70.4 Aspirin 91.3 Other antiplatelet 24.8 Potassium-sparing diuretic 9.0 Other diuretic 50.3 Statin 34.1 *stopped prior to randomization Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349:

5 Chronic HF GISSI-HF: comorbidità (n pts) IMA pregresso 42.0% Ictus pregresso 5.2% Arteriopatia obliterante periferica 9.4% BPCO 22.6% Disfunzione renale (egfr 60 ml/min/1.73m 2 ) 38.1%

6 Fumatore 14.5% Ipertensione 55.0% Diabete Mellito 28.5% Fattori di rischio (n pts) Procedure terapeutiche pregresse (n pts) Rivascolarizz. Pregressa (PCI/CABG) 27.7% ICD 7.1% PM 12.7%

7 Question 1 Which are the well documented risk factors of cardiovascular diseases?

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10 Inter Heart Study: the relevant risk factors Risk factors Smoking Diabetes Ipertensione Abnormal lipids Obesity Psycosocial stress Protective factors Consumption of fruits, vegetables Consumption of alcohol Regular physical activity Easily measurable risk factors are associated with more than 90% of the risk of AMI in this large global case-control study

11 Question 2 Are there new biomarkers that can really add predictive value to the simple, documented risk factors of cardiovascular diseases?

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15 Statements 2 and 3 Easily measurable risk factors can explain more than 90% of the risk of CV diseases The use of contemporary biomarkers add only moderately to standard risk factors for risk assessment of individual persons

16 Questions 3 and 4 What about: Renal dysfunction? COPD?

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19 % 30% 20% 10% 23.3% Survey on ACUTE HEART FAILURE In-Hospital all-cause mortality 17.9% 12.0% 8.3% 3.2% 3.6% 3.3% 2.0% 5.0% 0% < >=90 egfr n. of pts Adjusted OR (by 10 ml/min) 0.89; 95% CI ANMCO Research Center

20 Relationship between egfr and LV remodelling (VALIANT Trial, still unpublished data)

21 COPD

22 COPD Val-HeFT Trial Eventi clinici a 2 anni di follow-up No COPD COPD Mortalità totale Ospedal per HF P value < <0.0001

23 Statements 4 and 5 Renal dysfunction and COPD independently worsen the outcome of patients with CV diseases These co-mordidities, generally scarcely considered by cardiologists, are between the strongest negative prognostic indicators in patients with CV diseases

24 Question 5 Since we are not dealing with individual problems but with a disease of the society, shall we extend medicalization to the large majority of the population? To solve this issue, is better a doctor or a politician/urbanist?

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26 From the Congress for the New Urbanism (CNU) charter: Many activities of daily living should occur within walking distance, allowing independence to those who do not drive, especially the elderly and the young Interconnected networks of streets should be designed to encourage walking, reduce the number and length of automobile trips Schools should be sized and located to enable children to walk or bicycle Streets and squares should be comfortable and interesting to the pedestrian. Properly configured, they encourage walking Use of train and light rails should be promoted. Instead of more highways and roads...

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28 Fighting Sloth

29 From dreams to practice: when a pharmacological treatment is necessary Polypill More research is needed One pill with multiple actions ARBs/ACE-I Statins New hypotheses of research?

30 Conclusions Look for/intervene on easily measurable and modifiable risk factors Contemporary biomarkers scarcely add predictive value in individual persons Renal function and COPD should be routinely considered in both CV clinical practice and research

31 Conclusions A pharmacocentric approach is not the only solution for preventing CV diseases From one side, a tailored individual intervention ( omics?) on multiple risk factors should be pursued From the other side, a drastic change of current way of life is likely the best solution for minimizing the burden of complex comorbidities

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33 ANMCO Research Center Survey on ACUTE HEART FAILURE In-hospital all-cause mortality p< % 3.5% 60 ml/min <60 ml/min

34 Dati amministrativi: anno 2002 l impatto della COPD sugli eventi CV nel follow-up a 1 anno % +26% +35% Mortalità totale IMA, stroke, HF ReOsp per HF Adjusted p value

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38 Prevalence of microalbuminuria Population N. Subjects Prevalence Reference US Population 22,244 Males: 6.1% Females: 9.7% NHANES III Survey Jones et al., AJKD 2002 Non-hypertensive, nondiabetic individuals 1,568 6% Framingham Heart Study Arnlov et al., Circulation 2005 Patients at high CV risk 9,282 Non-diabetics: 14.7% Diabetics: 32.2% HOPE Study Gernstein et al., Diabetes Care 2000

39 91 patients with chronic HF, NYHA III-IV Mean age: 69 years Random urine spot samples Prevalence of microalbuminuria: 29/91 = 32% No association with biomarkers (BNP, renin, angiotensin II, aldosterone) or renal function (egfr).

40 Microalbuminuria and COPD

41 Microalbuminuria and glomerular function egfr calculated with the simplified MDRD equation

42 Microalbuminuria and C-reactive protein High sensitive CRP measured by immunoturbidimetry in a subset of 711 patients

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44 Prevalence of microalbuminuria (2,131 patients with chronic HF) Albuminuria UACR 300 mg/g n= % 19.9% 74.7% Normal UACR < 30 mg/g n=1592 Microalbuminuria UACR mg/g n=423

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46 Survey on ACUTE HEART FAILURE 30% 23.3% % 20% 10% 17.9% 12.0% 8.3% 3.2% 3.6% 3.3% 2.0% 5.0% 0% < >=90 egfr n. of pts Adjusted OR (by 10 ml/min) 0.89; 95% CI ANMCO Research Center

47 Dati amministrativi: anno 2002 l impatto della COPD sugli eventi CV nel follow-up a 1 anno % +26% +35% Mortalità totale IMA, stroke, HF ReOsp per HF Adjusted p value

48 Val-HeFT Trial Eventi clinici a 2 anni di follow-up No COPD COPD Mortalità totale Ospedal per HF P value < <0.0001

49 Easily measurable risk factors are associated with more than 90% of the risk of AMI in this large global case-control study Results are consistent across all geographic regions and ethnic groups of the world, men and women, and young and old Priorities can differ between geographic regions because of variations in prevalence of risk factors and disease and economic circumstances However, these results suggest that approaches to prevention of coronary artery disease can be based on similar principles throughout the world Therefore, modification of currently known risk factors has the potential to prevent most premature cases of AMI worldwide