1. Kimberly Dunbar, PA-S2 Follow-up of Cardiovascular Risk Markers in Hypertensive Patients Treated with Irbesartan: Results of the i-SEARCH Plus Registry Ulrich Tebbe, MD; Peter Bramlage, MD; Stephan Luders, MD; Alessandro Cuneo, MD; Peter Sistig, PhD; Fokko de Haan, MD; Roland Schmieder, MD; Michael Bohm, MD; W. Dieter Paar, MD; Jochen Schrader, MD The Journal of Clinical Hypertension 12 (2010) 909-916

2. Overview  Biomarkers  Substances found in the blood, body fluid, or tissues that can provide information regarding disease occurrence and prognosis as well as efficacy of treatment

3. Overview  Microalbuminuria (MAU)  Small amount of albumin excreted in the urine  Normal urinary albumin excretion is <30 mg/day  Defined as 30-300 mg/day  Reliable indicator for end organ damage  Recommended for identifying high-risk patients in hypertension treatment  Presence leads to use of ACE-Is and ARBs, which have shown to have an effect on biomarkers

4. Overview  Highly sensitive C-reactive protein (hsCRP)  Inflammatory marker for early atherosclerosis  Elevated hsCRP associated with increased risk of CVD  Irbesartan has been shown to decrease levels  Normal: <1 mg/L  Intermediate CVD risk: 1-3 mg/L  High CVD risk: 3-10 mg/L  Systemic inflammation: >10 mg/L

5. Overview  N-terminal pro-brain natriuretic peptide (NT-proBNP)  preproBNP is cleaved into BNP and inactive NT-proBNP  Normal: <100 pg/mL  Elevated levels indicate ventricular expansion and volume overload  Commonly used to diagnose and evaluate heart failure  Also thought to be an important risk marker in CVD

6. Objective  To determine risk of total mortality and cardiovascular events in relation to baseline values of MAU, NT-proBNP, and hsCRP  Mortality and cardiovascular events defined as:  Newly diagnosed CAD  Myocardial infarction  Unstable angina pectoris  Stroke/TIA

7. Design  Prospective study  1649 patients  43.2% women, 56.8% men  Arterial hypertension (≥140/90) at baseline  Prescribed Irbesartan  Followed for 12 months

8. Patients  ≥ 18 years old  No contraindications to Irbesartan alone or with HCTZ (12.5mg)  Exclusion Criteria:  Impaired renal function  Serum creatinine ≥2.0 mg/dL  UTI  Febrile infection  Menstruation  Pregnancy  Drug or alcohol abuse

9. Details  Mean age of patients at baseline was 61.4±11.3 years  Mean BP at baseline was 159.8±20.1/93.4±11.9  46.9% received irbesartan alone  51.1% received irbesartan/HCTZ 12.5mg  Median biomarkers at baseline  Albumin/Creatinine ratio – 9.9  hsCRP – 2.46  NT-proBNP – 89.28

10. Results  Mean BP at endpoint was 137.6±17.8/83.0±10.3  MAU positive (≥20 mg/g) at baseline was associated with an increased risk for CV events  CV events at 12 months  Total of 33  9 newly diagnosed CAD  1 MI  5 stroke/TIA  5 deaths  13 hospitalized during follow-up

11. Results  No influence of hsCRP or NT-proBNP on endpoint  A significant correlation of NT-proBNP with total death was corrected after adjusting for age and presence of MAU

12. Correlations among risk markers  MAU-positive patients at baseline AND those who developed MAU had higher median values of both hsCRP and NT-proBNP compared to those who developed AND remained MAU-negative

13. Conclusion  Microalbuminuria is predictive of future cardiovascular events in hypertensive patients despite treatment with angiotensin receptor blockers and is superior to hsCRP and NT-proBNP in predicting cardiovascular risk.

14. Limitations  Non-randomized open study  Follow-up was only 12 months  No control group

15. Level of Evidence

16. References  Tebbe U, Bramlage P, Luders S et al. Follow-up of Cardiovascular Risk Markers in Hypertensive Patients Treated with Irbesartan: Results of the I- SEARCH Plus Registry. The Journal of Clinical Hypertension. 2010; 12: 909-916.