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

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

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

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

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

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

Design

Prospective study 1649 patients 43.2% women, 56.8% men Arterial hypertension (≥140/90) at

baseline Prescribed Irbesartan Followed for 12 months

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

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

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

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

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

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.

Limitations

Non-randomized open study Follow-up was only 12 months No control group

Level of Evidence

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.