Journal of Human Hypertension (2002) 16, 249–254 2002 Nature Publishing Group All rights reserved 0950-9240/02 $25.00 www.nature.com/jhh ORIGINAL ARTICLE Microalbuminuria is associated with unfavourable cardiac geometric adaptations in essential hypertensive subjects C Tsioufis1, C Stefanadis1, M Toutouza1, I Kallikazaros1, K Toutouzas1, D Tousoulis1, C Pitsavos1, V Papademetriou2 and P Toutouzas1 1Department of Cardiology, University of Athens, Hippokration Hospital, Athens, Greece; 2VAMC and Georgetown University Medical Centers, Washington DC, USA We sought in this study to examine the relationship tively correlated to LVMI (r = 0.46, P Ͻ 0.001) and relative between microalbuminuria and cardiac geometry since wall thickness (r = 0.47, P Ͻ 0.001). In the entire popu- a slight increased urinary albumin excretion (UAE) and lation, normal LV geometry, concentric LV remodelling, increased left ventricular (LV) mass have both been eccentric and concentric LV hypertrophy was found in identified as predictors of cardiovascular events in 34%, 33%, 12% and 21%, respectively. The prevalence hypertensive subjects. For this purpose, microalbumin- of normal LV geometry was significantly higher in nor- uria was determined in three non-consecutive 24-h urine moalbuminuric compared with microalbumnuric sub- samples as UAE of 20–200 mg/24 h in a group of 249 jects (55 vs 14%, P Ͻ 0.001) while the prevalence of untreated hypertensive subjects. Echocardiographic concentric LV hypertrophy was significantly higher in classification of patients into LV geometric patterns was microalbuminuric compared with normoalbuminuric based on relative wall thickness values and on gender- subjects (32 vs 5%, P Ͻ 0.0001). Multiple regression specific values for LV mass index (LVMI). The group of analysis revealed that concentric LV hypertrophy was patients with microalbuminuria (n = 119) was matched significantly associated with increased values of UAE for age, sex, body mass index, smoking status and and mean arterial pressure. In conclusion, the higher plasma cholesterol level with the group of patients with- prevalence of unfavourable LV geometric patterns in out microalbuminuria (n = 130). Subjects with micro- hypertensive subjects with microalbuminuria compared albuminuria had significantly increased LVMI (111 vs with those without microalbuminura, may account for 90 g/m2, P Ͻ 0.0001), relative wall thickness (0.46 vs the worse cardiovascular outcomes associated with the 0.41, P Ͻ 0.001) and office systolic and diastolic blood presence of an increased UAE in hypertensive subjects. pressure (161 vs 148 and 101 vs 97 mmHg, respectively, Journal of Human Hypertension (2002) 16, 249–254. DOI: P Ͻ 0.005). For the pooled population, UAE was posi- 10.1038/sj/jhh/1001379 Keywords: microalbuminuria; cardiac geometry; left ventricular hypertrophy Introduction non-diabetic patients with essential hyperten- sion.1,2,4–6 The pathogenic mechanisms leading A slightly elevated urinary albumin excretion microalbuminuric patients to this increased risk are (UAE), termed microalbuminuria, has been ident- still unknown; several studies have demonstrated an ified as an independent predictor of cardiovascular 1,2 association between microalbuminuria and athero- disease in major population-based cohort studies. genic cardiovascular risk factors, endothelial dys- Indeed, it is well established that microalbuminuria function, impaired aortic mechanics and increased can be considered predictive of the development of left ventricular (LV) mass.2,5–8 Left ventricular hy- overt proteinuria and of cardiovascular mortality in pertrophy is another manifestation of pre-clinical 3 diabetic patients. The same adverse prognostic con- disease with well-defined prognostic meaning for clusion seems to emerge from recent research in cardiovascular complications. Furthermore, identi- fication of various geometric patterns of LV hypertrophy furthers stratifies cardiovascular Correspondence: C Tsioufis, 4 Athanasiou Diakou Street, 15127 risk.9,10 The aim of the present study, therefore, was Melissia, Greece. Fax: 00 30 1 7784590 Received 10 May 2001; revised 13 September 2001; accepted 22 to examine the relation between microalbuminuria November 2001 and the patterns of LV geometry in untreated non- diabetic hypertensive subjects. Microalbuminuria and cardiac geometry C Tsioufis et al 250 Subjects and methods Sonos 2500 ultrasound imager equipped with a 2.25–5 MHz transducer. Images were recorded on Study population super VHS videotapes and measurements were sub- The population in our study consisted of subjects sequently performed off-line by two independent with essential hypertension, aged 30 and 70 years operators, blinded to the patients’ demographics and referred to the outpatient hypertension unit. Patients BP status. Two-dimensional guided M-mode echo- with uncomplicated essential hypertension, stages cardiography was performed at the parasternal long- I–II were included in the study if they were newly axis view, and LV end-systolic systolic and diagnosed (within the previous 2 years) and had end-diastolic dimension, as well as intraventricular never been previously treated. Presence and severity septum and posterior wall thickness were measured of hypertension were determined on the basis of as the mean from five consecutive cardiac cycles, in office blood pressure (BP) measurements obtained accordance to the recommendations of the American by sphygmomanometer during three consecutive Society of Echocardiography.12,13 Subsequently, visits scheduled 3 weeks apart, according to the re- relative wall thickness was calculated using the fol- commendations of the JNC-VI.11 To confirm essen- lowing formula: (septal wall thickness + posterior tial hypertension, patients were assessed by using wall thickness)/(LV end-diastolic diameter).14,15 LV conventional clinical criteria and laboratory tests. In mass was calculated by the formula introduced by addition, all patients underwent renal ultrasono- Devereux et al: (0.80 × 1.04[{intraventricular septum graphy to confirm the presence of normal kidney thickness + posterior wall thickness + left ventricu- size without cortical scarring or signs of obstructive lar end diastolic diameter}3 − left ventricular end uropathy. Exclusion criteria included overt pro- diastolic diameter] + 0.6) and was indexed for the teinuria, detectable by urine dip strip test, diabetes body surface area (LVMI). LV hypertrophy was con- mellitus, increased values of plasma creatinine, fam- sidered present if LVMIϾ104 g/m2 in women and iliar hypercholesterolaemia, history of any cardiac Ͼ116 g/m2 in men.15,16 Normal geometry was con- disease or other clinically significant concurrent sidered when LV mass did not extend the above gen- medical condition. Women receiving oral contracep- der specific values. Concentric LV hypertrophy was tives or long-term oestrogen replacement therapy considered present if relative wall thickness was were also excluded. Of the 310 individuals screened Ͼ0.43 and eccentric LV hypertrophy when relative for the study, 249 subjects (142 males), mean age wall thickness was р0.43.15 Concentric remodelling 52 ± 10 years, fulfilled all inclusion and exclusion was considered present in patients with normal criteria and consisted our study population. LVMI and relative wall thickness р0.43. All patients gave written informed concept for The inter-observer variability in our laboratory participation. The study protocol was approved by was 9.65% for LVMI and 8.5% for relative wall the ethics committee of our institution. thickness. Measurements obtained by the two observers were averaged and used for data analysis. Determination of UAE The study patients were asked to collect three non- Statistical analysis consecutive 24-h urine samples (from 8 am to 8 am) for the determination of UAE, as has been pre- Data is expressed as mean ± s.d. Since the 24-h UAE viously described.7 Urinary albumin concentrations data were skewed, values were logarithmically were determined by an immunonephelometric tech- transformed prior to statistical testing. Significant nique with a limit of detection of 0.4 mg/dl and an differences between the two groups were determ- interassay variation of 3.5%. Based on mean UAE in ined using the Student’s independent samples t-test the samples, the study patients were divided in or the ␹2 test where appropriate. Multiple linear those with microalbuminuria (mean UAE 20– regression analysis, with inclusion criteria at the 200 mg/24 h) and in those without microalbumin- 0.01 level and exclusion criteria at the 0.05 level, uria (mean UAE Ͻ20 mg/24 h). was used to evaluate the relation of clinical, demo- In addition to the above initial laboratory workup, graphic and haemodynamic parameters with LVMI. all selected patients underwent measurement of Also, a logistic regression model was used to ident- plasma lipids, which included total cholesterol, ify significant relations between each type of LV high-density lipoprotein cholesterol and triglycer- geometry and clinical, demographic and haemody- ides, using established techniques. Finally, patients namic parameters. Spearman correlation was perfor- were questioned about their smoking habbits. Smok- med to determine correlations between any of the ers were identified as those patients consuming one parameters. An analysis of covariance (ANCOVA) or more cigarettes per day. was performed in order to detect significant differ- ences of LVMI between patients with and without microalbuminuria, after the adjustment of a number