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High-normal serum creatinine concentration is a predictor of cardiovascular risk in essential hypertension
G Schillaci1, G Reboldi, P Verdecchia
1Unit of Internal Medicine, Angiology, and Arteriosclerosis, Department of Clinical and Experimental Medicine, University of Perugia Medical School via Brunamonti, 51, 06122 Perugia, Italy. skill@unipg.it
Insights
Serum creatinine levels within the normal range predict cardiovascular events in hypertensive patients. Even slight increases in creatinine indicate higher cardiovascular risk, independent of other factors.
Area of Science:
- Cardiology
- Nephrology
- Hypertension Research
Background:
- Serum creatinine is a marker for target organ damage in hypertension.
- Its role in cardiovascular risk stratification within normal ranges is unexplored.
Purpose of the Study:
- To investigate if serum creatinine levels within the reference range predict cardiovascular morbidity in essential hypertension.
Main Methods:
- Followed 1829 hypertensive patients (normal creatinine) for up to 11 years.
- Collected data on demographics, blood pressure, and cardiac health.
- Used multivariate Cox models to analyze cardiovascular event predictors.
Main Results:
- Cardiovascular event rates increased with higher creatinine quartiles (P=.003).
- Creatinine was an independent predictor of cardiovascular events (P=.01) after adjustments.
- A 20-micromol/L creatinine increase correlated with 1.30 excess risk.
Conclusions:
- Serum creatinine within the reference range predicts cardiovascular morbidity in essential hypertension.
- This prognostic value remains significant even after adjusting for major confounders like blood pressure and left ventricular hypertrophy.
Background:
Determination of serum creatinine concentration is recommended in all patients with hypertension as a marker of target organ damage. However, the possibility that creatinine values within the reference range might contribute to stratification of cardiovascular risk in essential hypertension has never been tested.
Patients And Methods:
In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale Study, for up to 11 years (mean, 4 years) we followed up 1829 white patients with hypertension (mean +/- SD age, 51 +/- 12 years; 53% men; office blood pressure, 157/98 mm Hg) free of cardiovascular events and with normal pretreatment creatinine levels (men, <136 micromol/L [<1.5 mg/dL]; women, <120 micromol/L [<1.4 mg/dL]) who also underwent 24-hour blood pressure monitoring and electrocardiography before therapy.
Results:
During follow-up, there were 175 fatal or nonfatal major cardiovascular morbid events (2.4 per 100 patient-years). Event rate increased progressively from the first to the fourth sex-specific quartiles of creatinine distribution (1.5, 2.3, 2.3, and 3.5 per 100 patient-years; P =.003 by log-rank test). After adjustment (in a multivariate Cox model) for age, sex, diabetes, cholesterol, smoking, left ventricular hypertrophy, and 24-hour pulse and mean blood pressures (P<.05 for all), creatinine concentration was an independent adverse predictor of cardiovascular morbid events (P =.01). The observed excess risk was 1.30 (95% confidence interval, 1.07-1.59) for a 20-micromol/L (0.23-mg/dL) increase in creatinine concentration.
Conclusions:
A serum creatinine value within the reference range is a predictor of cardiovascular morbidity in white patients with essential hypertension. Its prognostic value persists after adjustment for several powerful confounders, including average 24-hour blood pressure and left ventricular hypertrophy.