Trends in Hypertension Hypertensive Emergency Case Decision and Classification

1. Layered Procedures inHypertensive EmergenciesDr. Klaus Fiedler IHAMB, University of Basel, Basel, Switzerland

2. Trends in Hypertension Hypertensive Emergency Case Decision and Classification Therapy and Cardiovascular Complications Primary Events Secondary Events Comparison of Primary and Secondary Events in this Study Conclusions

3. Systolic blood pressure in mmHg (not age-standardized) In 180 countries Trends in Hypertension Time period 80 – 09 Values from WHO

4. Average systolic in mmHg (not age-standardized) coefficientofregression (b) Blood Pressure Mean: Men p<0.05 Average systolic values from 1980 to 2009 from WHO

5. Male Blood Pressures 1980 – 2009 Systolic in mmHg

6. Average systolic in mmHg (not age-standardized) coefficientofregression (b) Blood Pressure Mean: Women p<0.05 Average systolic values from 1980 to 2009 from WHO

7. Female Blood Pressures 1980 – 2009 Systolic in mmHg

8. Simple Trends in Blood Pressure Blood Pressure coefficient of regression female against male 1.43 (CI 1.36-1.52); p=0.001 Female Male betas of linear predictions (male and female) based on raw values from WHO (1980 – 2009)

9. Simple Trends in Blood Pressure • if the development is towards higher values of blood pressure • (or negligible in male), female trends are ever so often more rapid • if the development is towards lower values of blood pressure, it is • usually more rapid in the female sex • female trends are highly significant • Þ countries with largest gender gaps are… • Top 2% Burkina Faso towards higher values • Mali • Niger • Nigeria • Top 2% Czech Republic towards lower values • Spain • Estonia • Malta

10. Physiology: Male andFemalewith 3 Parameters Countries CI PCA Blood Glucose Blood Pressure BMI b = 0.85 (CI 0.78-0.92) Coefficient Female • women’s values are non-uniformely distributed amongst different • countries • men’s values are uniformely distributed amongst different • countries Coefficient Male

11. Non-linear predictions; Average systolic blood pressure Add to baseline of 2009 (in mmHg) Trends in Hypertension: 2016 Predictions based on 1980 – 2009 Raw Values from WHO

12. Trends in Hypertension Hypertensive Emergency Case Decision and Classification Therapy and Cardiovascular Complications Primary Events Secondary Events Comparison of Primary and Secondary Events in this Study Conclusions

13. available patient cohort study from May 2008 in Kanton Basel (BS, BL) and • Luzern • inclusion criteria: blood pressure >180 mmHg/>110 mmHg, age > 20 y • discriminant analysis, logistic regression, categorical regression, multi • layer perceptrons • primary care questionnaire • … in addition to Age and Gender, data on Blood pressure, Drugs, Emergency therapy, Follow-up • therapy, Cardiovascular risk factors were requested to be answered. Further questions referred • to Accompanying conditions and the History of cardiovascular complications, Cardiovascular • complications within 3 months • 1 year follow-up • … Cardiovascular events, Follow-up therapy changes anddata on newly described Cardiovascular • risk factors wererequested to be answered Hypertensive Emergencies

14. Prevalence Hypertension Prevalence in the Elderly Age group (approx.) 65-74 Wolf-Maier et al. (2003); Kearney et al. (2005); Pitsavos et al. (2006) ; eurostat.ec.europa.eu (2008); National Health and Nutrition Survey of Japan (2006) and WHO

15. Test: Hypertensive Emergencies and Case Decision Modelling of the „clinical decision“ path E - H E: Emergency Therapy H: Hospitalization -E -H E + H H - E

16. Hypertensive Emergencies: Symptoms included in the statistics, yet, do not count as overt symptoms * Does not lead to Emergency or Urgency classification

17. Differential Diagnosis Brennan et al. 2010, Critical Care Study Guide

18. time course 18.4 months 164 patients included „Available Patient Cohort“ Study blood pressure determination 14 months n= 137 lost to follow-up n=26 8 patients died

19. 8 Cases were selected 6: Other 5: Congestive Heart Failure 4: TIA 3: Cerebrovascular Insult 2: Occlusive PAD 1: Coronary Artery Disease 0: None Cardiovascular Differential Diagnosis: Reevaluation No Yes Hypertension

20. Hospitalization of Patients

21. sex m f Summary of Patient Data number Anzahl Emergency Urgency Asymptomatic Classification

22. no therapy monotherapy combination therapy Therapy by Emergency Classes number Emergency Urgency Asymptomatic Class

23. hypertensive emergency 1 h 6 h 12 h 6 days 15 days 3.5 months 14 months Time-Series systolic diastolic

24. Cardiovascular Risk Factors percentage of patients none obesity smoking family history hyperlipidemia lack of exercise Diabetes mellitus renal insufficiency

25. Sex-Specific Distribution Factors Diabetes mellitus renal dysfunction physical inactivity hyperlipidemia obesity smoking cumulative risk factors m f Sex

26. Cardiovascular Risk Factors After 1 Year

27. Accompanying Medical Conditions percentage of patients None NSAR Stress Pain OSAS Asthma Infection Alcoholism Non-compliance Increase in body weight White Coat hypertension

28. Patients and Frequency correlative evidence shows… • first hypertensive emergencies occur often with new patients • White Coat hypertensive patients show fewer symptoms upon examination • symptoms correlate with stress, NSAR medication and infects

29. Neural Network The network identified 92% of the patients with acute myocardial infarction, 96% of the patients without infarction. When all patients with the ECG evidence of infarction were removed from the cohort, the network correctly identified 80% (modified from Baxt 1990)

30. Neural Network Key Question “Does the evaluation contain previously inapparent information that can be used to improve on the diagnostic accuracy of predicting…” Baxt, 1990 • hypertension • gender • lack of exercise / obesity

31. Retained Parameters in Logistic Regression Class E E E E E U E U p= 0.020 0.035 0.042 0.017 0.000 0.021 0.004 0.046 Asymptomatic Stress NSAR Infection New patient White Coat hypertension White Coat hypertension History of cardiovascular events History of cardiovascular events n=164 Pseudo R2=0.321, goodness of classification 64%

32. Dynamic Scaling of Emergency Classes Separation of U and A requires use of Symptom variable?

33. Dynamic Scaling of Emergency Classes „The Diagnostic Gap“ „Structural Equation“ model without parameters

34. Classification in Hypertensive Emergencies Model unifying 7 different „output functions“ counting 2400 Top 10% E 79.8% +/-15.8% U 96.9% +/-2.5% A 96.3% +/-2.4% Total 95.0% +/-2.4% (+/- SD) Importance proposed cut-off max. epochs 500

35. Optimized Top 500 Models of 2400 Hidden Layer AF Hyperbolic tangent 321 Sigmoid 182 Ouput Layer AF Hyperbolic tangent 83 Identity 93 Sigmoid 37 Softmax 290 AUCs ≥ 0.986

36. Optimized Top 500 Models of 2400 Model unifying 7 different „output functions“ - Top 500 E 100.0% +/-0.0% U 97.7% +/-1.1% A 99.6% +/-0.7% Total 99.0% +/-0.6% (+/- SD) Importance

37. Classification in Discriminant Analysis Emergency Urgency Asymptomatic Emergency Function 2 Asymptomatic Urgency Function 1

38. Classification in Discriminant Analysis symptoms history of cardiovascular events age White Coat hypertension new patient hypertension first hypertensive emergency sex explained variance of 200 NSAR infection variance model 1 model 2 model 3 pain stress proposed cut-off

39. Hypertensive Emergency: Goodness of Classification Symptoms were not introduced in logistic regression

40. Treatment

41. Patient Recall? Seemed not absolutely necessary…

42. Drug History and Emergency Therapy • p <0.05 • Cardiovascular treatment track • ACE inhibitors in drug history lead to a significantly higher prescription rate of • sedatives • previous treatment with ARB results in frequent emergency treatment with ARB • ARBs in drug history lead to infrequent therapy with ACE inhibitors in hypertensive • emergencies • patients receiving ARB in emergency treatment regularly receive ARB in follow-up • treatment

43. Adverse Effects in Therapies Drugs causing drug-induced hypertension and hypertension treatment

44. Combination Therapy Therapy: According to Guideline Mono-Therapy Mann-Whitney U Test

45. hypertensive emergency 1 h 6 h 12 h 6 days 15 days 3.5 months 14 months systolic diastolic Time-Series blood pressure recommendation 1 to 2 h and 2 to 6 h

46. Acutely treated patients Time-Series: Emergency mmHg

47. Acutely treated patients Time-Series: Urgency mmHg

48. Acutely treated patients Time-Series: Asymptomatic mmHg

49. Acutely treated patients Time-Series: Emergency mmHg

50. Acutely treated patients Time-Series: Urgency mmHg