ADMA, C-Reactive Protein, and Albuminuria in Untreated Essential Hypertension: A Cross-sectional Study

Tsioufis, Costas; Dimitriadis, Kyriakos; Andrikou, Eirini; Thomopoulos, Costas; Tsiachris, Dimitris; Stefanadi, Elli; Mihas, Costas; Miliou, Antigoni; Papademetriou, Vassilios; Stefanadis, Christodoulos

doi:10.1053/j.ajkd.2009.11.024

« Previous Next »American Journal of Kidney Diseases
Volume 55, Issue 6 , Pages 1050-1059, June 2010

ADMA, C-Reactive Protein, and Albuminuria in Untreated Essential Hypertension: A Cross-sectional Study

Costas Tsioufis, MD, PhD
- First Cardiology Clinic, University of Athens, Hippokration Hospital, Athens, Greece
- Address correspondence to Costas Tsioufis, MD, PhD, FESC, 43, Agias Marinas Str, 15127 Melissia, Athens, Greece
Kyriakos Dimitriadis, MD
- First Cardiology Clinic, University of Athens, Hippokration Hospital, Athens, Greece
Eirini Andrikou, MD
- First Cardiology Clinic, University of Athens, Hippokration Hospital, Athens, Greece
Costas Thomopoulos, MD
- First Cardiology Clinic, University of Athens, Hippokration Hospital, Athens, Greece
Dimitris Tsiachris, MD
- First Cardiology Clinic, University of Athens, Hippokration Hospital, Athens, Greece
Elli Stefanadi, MD
- First Cardiology Clinic, University of Athens, Hippokration Hospital, Athens, Greece
Costas Mihas, MD
- First Cardiology Clinic, University of Athens, Hippokration Hospital, Athens, Greece
Antigoni Miliou, PhD
- First Cardiology Clinic, University of Athens, Hippokration Hospital, Athens, Greece
Vassilios Papademetriou, MD, PhD
- Hypertension and Cardiovascular Research Clinic, Veterans Affairs Medical Center, Washington, DC
Christodoulos Stefanadis, MD, PhD
- First Cardiology Clinic, University of Athens, Hippokration Hospital, Athens, Greece

Received 29 June 2009; accepted 16 November 2009. published online 02 March 2010.

Background

Asymmetric dimethylarginine (ADMA) and subclinical inflammation are associated with atherosclerosis progression, whereas microalbuminuria is an established index of hypertensive organ damage.

Study Design

Cross-sectional.

Setting & Participants

In an outpatient hypertensive unit, 296 nondiabetic and untreated participants with hypertension were studied. Participants with atherosclerotic cardiovascular disease, severe valvulopathy, congestive heart failure, presence of neoplastic or other concurrent systemic disease, atrial fibrillation, serum creatinine level > 1.5 mg/dL in men and > 1.4 mg/dL in women, and urinary albumin excretion > 300 mg/24 h were excluded.

Predictors

ADMA and high-sensitivity C-reactive protein (hs-CRP) levels.

Outcome Variable

Albuminuria assessed using albumin-creatinine ratio (ACR).

Measurements

Participants underwent ambulatory blood pressure monitoring, echocardiography, routine assessment of metabolic profile, ADMA, and hs-CRP, whereas ACR was determined as the mean of 3 values in nonconsecutive morning spot urine samples.

Results

64 participants had an ACR of 30-300 mg/g. Stratification based on ADMA level showed that participants with hypertension in quartile [Q] 4 compared with those in Q3, Q2, and Q1 showed the highest ACRs (53.2 vs 31.2 vs 30.4 vs 16.7 mg/g; P < 0.008 for all). Moreover, stratification based on hs-CRP level showed that participants with hypertension in Q4 (69.8% had microalbuminuria) showed the highest ACRs (72.2 vs 25.6, 16.2, and 19.2 mg/g for Q3, Q2, and Q1, respectively; P < 0.008 for all). Stepwise regression analysis showed that age, 24-hour systolic blood pressure, hs-CRP level, ADMA level, and the interaction of hs-CRP with ADMA were independent predictors of ACR (R² = 0.674; P < 0.001).

Limitations

Cross-sectional study.

Conclusions

In patients with untreated essential hypertension, increased hs-CRP and ADMA levels are associated with microalbuminuria, suggesting the involvement of inflammation and endothelial dysfunction in vascular and kidney damage.

Index Words: Endothelium, inflammation, kidney, atherosclerosis, hypertension