1. CVD and co-morbidities What are the priorities? G.J. Geersing, General Practitioner MD PhD Julius Center UMC Utrecht EPCCS conference 2014 Groningen

2. This presentation Multi-morbidity and primary care medicine Consultation: farmer Loeks, 82 years of age. Implications for clinical research What are the priorities?

3. Miss Sparrow, 76 years Eccentric personality Severe presbyacusis Recurrent UTI / incontinence Hypertension Severe osteoarthritis Atrial fibrillation eGFR 35 ml/min Possible heart failure (NT-proBNP = 236 pg/ml ) Medication: Omeprazol 20 mg Lisinopril 10 mg Digoxin 0,0125 mg Metoprolol 50 mg Aspirin 80 mg  BAFTA ≠ ASA!!  Renal function!!  Bad doctor!

4. Miss Sparrow and randomized trials Eccentric personality Severe presbyacusis Recurrent UTI / incontinence Hypertension Severe osteoarthritis Atrial fibrillation eGFR 35 ml/min Possible heart failure (NT-proBNP = 236 pg/ml ) Medication: Omeprazol 20 mg Lisinopril 10 mg Digoxin 0,0125 mg Metoprolol 50 mg Aspirin 80 mg  BAFTA ≠ ASA!!  Renal function!!

5. EBM in crisis?

6. Multi-morbidity and its causes. Epidemiology of multimorbidity and implications for health care, research, and medical education. K. Barnett et.al. Lancet 2012 Lower SES 10-15 years earlier

7. Multi-morbidity: the price of succes?

8. Multi-morbidity in COPD Prognostic studies in COPD

9. Example I in COPD (sec care). Comorbidity and risk of mortality in patients with COPD. M. Divo, et.al. Am. J. Respir. Crit. Care Med. 2012

10. Example II in COPD (prim care). The importance of cardiovascular disease for mortality in patients with COPD: a prognostic cohort study. J. Zangh et.al. Family Practice 2011.

11. Multi-morbidity in heart failure Prognostic studies in HF

12. Example in heart failure. Noncardiac comorbidity increases preventable hospitalizations and mortality among medicare beneficaries with chronic heart failure. J.B. Braunstein. JACC 2003.

13. Multi-morbidity in AF IPD Rx studies in AF

14. Beta-blockers in AF with heart failure

15. Summary so far: Multi-morbidity: frequent, notably with increasing age Low SES: 10-15 years earlier. Important for patients!

16. Consultation: farmer Loeks, 82 years 65 years: myocardial infarction, CABG Depression ‘Chronic bronchitis’, history of smoking Hypertension 72 years: TKP, post-operative DVT Renal impairment, eGFR 30 ml/min. Medication: ASA 80 mg, simva 40 mg, HCT 12.5 mg, metoprolol 50 mg mga, atrovent, pcm zn.

17. Farmer Loeks 82 years. “Doc, for some time now I am experiencing shortness of breath. About 10 days ago it suddenly got worse. I also started to cough, and had some pain on inspiration. Fever? No, I don’t think so doc…” RR 160/90, HR 105/min. Lungs: rales, some wheezing. COPD with pneumonia? Heart failure? Pulmonary embolism? What tests and/or biomarkers do I need to perform?

18. TESTS CDR and BNP in heart failure 721 patients with suspicion of heart failure, referred by GP to ‘rapid-access clinic’. The diagnostic values of physical examination and additional testing in primary care patients with suspected heart failure. J.C. Kelder, et.al. Circulation 2011

19. TESTS CDRs/decision tools in COPD.  173/357 (48%) patients ‘low risk’  NPV in ‘low risk’ group 94%

20. TESTS … CRP added value in suspected pneumonia.  c-statistic ‘only’ signs and symptoms = 0.70  combined with CRP: increase of c-statistic to 0.78

21. TESTS … and for suspected pulmonary embolism.  272/598 (45%) patients ‘low risk’  NPV in ‘low risk’ group 98.5% Wells ≤ 4 plus D-dimeer negative  PE unlikely

22. CDRs and biomarkers; implications for clinical research Performance often summarized in one or two values (c- statistic, sens/spec, predictive values)  Only true for average patient!  Influence age and co-morbidity?  Age-dependent cut-off D-dimer.

23. OUTCOME Concurrent presence of COPD and HF 405 patients with GP diagnosis of COPD (65+). Screening for unknown heart failure.  Diagnostic model to recognize HF in COPD patients Recognizing heart failure in elderly patients with stable COPD in primary care: cross sectional diagnostic study. F.H. Rutten, et.al. BMJ 2005 Unrecognized HF diagnosed in 83 patients (21%!)

24. PE diagnosis in COPD patients … “Our study findings suggest that one in four patients with an acute exacerbation of COPD may have PE. Thus, clinicians should consider PE in the diagnostic work-up of COPD exacerbations, especially in patients where the underlying etiology is not apparent.”

25. Back to our patient What do we know:  CDRs/tools: COPD, pneumonia, HF, and PE  Biomarkers: BNP, CRP, D-dimer  COPD, HF and PE simultaneously present COPD / Pneumonia  Age  Male  History of smoking  History of CVD  Wheezing  CRP? Heart failure  Age  History of CVD  Tachycardia  Rales  BNP? Pulmonary embolism  History of DVT  Tachycardia  D-dimer?

26. Back to our patient What we do not know yet / challenges:  Influence age and co-morbidity  Integral strategy  ‘typical’ GP problem

27. So, what are our priorities? Multi-morbidity important for patients … … for diagnosis, prognosis and treatment Challenge for clinical research!  Let us help miss Sparrow and become ‘good doctors’!