Prevalence of microalbuminuria in hypertension monitored in primary care

The objectives of the study were to evaluate the prevalence of microalbuminuria (MAU) in patients with hypertension, monitored in primary care and to analyse the correlation between MAU, risk factors and associated parameters. Material and methods. During 2010-2014 we evaluated a number of 910 patients from 19 family medicine offi ces of Timiş County. The general practitioners took a standardized history, performed a physical examination, measured height, weight, blood pressure, ABPM and heart rate, calculated body mass index and tested urine for MAU with Arkray test strips. The patients with hypertension and MAU were referred to diagnosis centres where they underwent echocardiography. Results. Aft er exclusion of patients with a history of renal disease and diabetes, MAU was present in 61 cases, 7.1%. The mean age of the MAU positive patients was 56±13.1 years, ranging from 29 to 79. The duration of hypertension was under 5 years in 4 (2.44%) patients, between 5-10 years in 35 (57.3%) and over 10 years in 22 (36%) Six patients with MAU (9.83%) had mild hypertension, 25 (40.9%) moderate and 30 (49.1%) severe hypertension. LVMI was 125 ± 28 g/m2 in the MAU absent group and 157 ± 56 g/ m2 in the MAU present group (<0.04). A stepwise logistic regression analysis showed signifi cant positive eff ects of 24 h systolic blood pressure, weight and LVH (p<0.001 for all comparisons) on MAU. No other variable had a signifi cant predictive eff ect on the presence or absence of MAU. Conclusions. In patients with essential hypertension MAU was present in 7.1%, with a higher prevalence in uncontrolled than in controlled hypertension. MAU was associated with high blood pressure levels, obesity and LVH.


INTRODUCTION
The European Society of Cardiology Hypertension Guidelines 2013 outline that it becomes more and more important to determine the target organ damage secondary to hypertension (1).The presence of MAU in pati ents with essenti al hypertension is related to cardiovascular morbidity and mortality, independent of other well-known risk factors.Microalbuminuria, in additi on to being an early sign of kidney damage, is oft en found in pati ents with essenti al hypertension.Even very low levels of microalbuminuria strongly correlate with CV risk, independent of the presence of other risk factors.Increased microalbuminuria indicates endothelial dysfuncti on and predicts end-organ damage, cardio-and cerebrovascular events and death (2,3).European guidelines recommend screening for microalbuminuria in pati ents with hypertension.Available tests for screening microalbuminuria as deep sti cks are sensiti ve and accessible.Early identi fi cati on of high-risk pati ents through detecti on of MAU allows selecti on of an aggressive treatment to slow disease progression.Anti hypertensive agents providing angiotensin II blockade are recommended for the treatment of hypertensive pati ents with MAU, as they assure eff ecti ve reducti on of MAU, blood pressure, and long-term preventi on of CV events beyond blood pressure reducti on.In this way a substanti ally reduced burden on healthcare resources can be obtained (4).

THE OBJECTIVES OF THE STUDY
• To evaluate the incidence of microalbuminuria in controlled and uncontrolled hypertension in primary care • To analyse the associati on between microalbuminuria, risk factors and other clinical data.

MATERIAL AND METHODS
We evaluated during 2010-2014 a total number of 910 hypertensive pati ents from 19 family medicine offi ces of Timiş County.Uncontrolled hypertension was defi ned as blood pressure ≥140/≥90 mmHg, when subjects reported lifestyle changes and medicati on consisti ng of ≥1 anti hypertensive drug.All family doctors implied in the study were instructed to use the same method of BP measurement and pati ent evaluati on.
The general practi ti oners performed the history, the physical examinati on and calculated the body mass index (BMI).A spot urine sample was tested for MAU at the family doctor's offi ce with Arkray test strips, that provide the following readings for urinary albumin: negati ve, ≥10 mg/L, ≥ 30 mg/L, ≥ 80 mg/L and ≥ 150 mg/L.Creati nine readings were for concentrati ons of 10 mg/dl, 50 mg/dl, 100 mg/dl, 200 mg/dl and 300 mg/dl (Fig. 1).Albumin creati nine rati o was calculated by intersecti on of their values (Fig. 2).The pati ents with hypertension and microalbuminuria were referred by their general practi ti oners to a diagnosis centre, where they underwent echocardiography.Only pati ents with complete measurements were included in the study.

STATISTICAL ANALYSIS
All the stati sti cal analyses were performed using the soft ware Stata 9.2.Data were presented as frequencies and percentages for qualitati ve variables and as mean ± SD for quanti tati ve variables.Diff erences between groups of variables were assessed with the Pearson x 2 for qualitati ve variables and the Student t test for quanti tati ve data.The independent variables

FIGURE 1. Interpretati on of albumin and creati nine concentrati ons by the colorati on of Arkray test strips
with p < 0.05, were considered as having stati sti cal signifi cance.

RESULTS
The blood pressure values of controlled and uncontrolled hypertension pati ents are presented in Fig. 3. Aft er exclusion of cases with a history of renal disease and with diabetes, MAU remained present in 61 cases (13.41%), of which 22 (4.3%) with controlled hypertension and 39 (9.11%) with uncontrolled (Fig. 4).
The characteristi cs of pati ents with and without MAU are presented in the Table 1.
The mean age of the pati ents was 56±13.1 years, ranging from 29 to 79, the majority being between 50 and 60 years.There were 3 cases (4.9%) with MAU under 40 years, 6 cases (9.8%) between 40-50 years, 31 cases (50.8%) between 50-60 years and 21 cases (34.4%) over the age of 60 years old.Age groups of pati ents with MAU are presented in Fig. 6.
The evoluti on in ti me of hypertension showed: a hypertension durati on under 5 years in 2.44%, between 5-10 years in 57.3% and over 10 years in 36% (Fig. 7).
The severity degree of hypertension was evaluated aft er the recommendati ons of the Hypertension Guidelines of the European Society of Cardiology published in 2013 (Fig. 8).
Depending on the hypertension profi le, the pati ents were divided in two groups: the dipper group of 27 (44.2%)and the non-dipper group, consisti ng of 34 pati ents (45.8%), whose hypertension fell less than 10% during the night ti me (Fig. 9).
Concerning the cardiovascular risk of the pati ents that associated MAU, 47 cases (77.8%) had a high and very high risk, 12 cases (19.6%) a moderate risk and 2 cases (3.2%) a low CV risk (Fig. 10).
The main cardiovascular risk factors among hypertensive subjects with MAU were: physical inacti vity in 60.6%, smoking in 21.3%, a family history of premature cardiovascular disease in24.5%,obesity in 40.98%, lipid disorders in 50.8% and metabolic syndrome in 52.4%.Left ventricular mass index was higher in MAU pati ents than in normal buminuria hypertensives.
A stepwise logisti c regression with MAU as the dependent variable and as independent variables age, gender, height, weight, BMI, 24 h systolic and diastolic blood pressure, left ventricular hypertrophy, showed signifi cant positi ve eff ects of 24 h systolic blood pressure   40%.Microalbuminuria also is found in 5 to 7% healthy individuals.The excreti on of albumin in the urine is related to the risk to develop cardiovascular disease (6).The Internati onal Survey Evaluati ng microalbuminuria by cardiologists in pati ents with hypertension (i-SEARCH) was undertaken in 26 countries around the world in a total of 1,750 sites to provide epidemiological data on the prevalence of MAU and its associati ons with established cardiovascular risk markers and disease.
Our study evaluated a populati on of hypertensive pati ents monitored by general practi ti oners.We found a total prevalence of MAU of 7.1% that was lower in controlled hypertension than in uncontrolled hypertension, dependent on-the level of 24 h average systolic blood pressure, bodyweight and left ventricular hypertrophy (7).
We recorded as in the SEPHAR II survey only in a minority of cases MAU, as the most important part of hypertensive pati ents didn't present this subclinical organ damage (7,8).
Many studies investi gated the relati onship between the number of cardiovascular comorbiditi es and the presence of MAU in hypertension.The prevalence of MAU increased from 54% in pati ents without cardiovascular comorbiditi es to 74% in the presence of more than 3 comorbiditi es.The conclusion is that in hypertensive pati ents at high cardiovascular risk, the prevalence and extent of MAU increases with the number of comorbiditi es (8,9).
Our data confi rm previous studies that have demonstrated a relati onship between albumin excreti on rate and the level of systolic blood pressure.As showed, most of the pati ents had severe hypertension with high cardiovascular risk.The positi ve relati on of MAU to bodyweight is demonstrated in some other surveys (10).Many clinical trials have not been able to demonstrate a signifi cant relati onship between MAU and age, aspect that requires further confi rmati on (11).
As in other studies, we found that LV mass is increased in pati ents with MAU and might quite well account for the observed increase in cardiovascular morbidity and mortality in pati ents with MAU.

CONCLUSIONS
Early signs of hypertensive nephropathy as MAU can be easily detected by general practiti oners with test strips.

DISCUSSIONS
Urine excreti on of albumin is highly variable, from nondetectable to milligrams and even grams of albumin.Microalbuminuria is defi ned as albumin excreti on of 30 to 300 mg/day (5).Microalbuminuria is highly prevalent in hypertensive and diabeti c populati ons, form 10 to

Severity degree of hypertension
Microalbuminuria was present in 7.1% of pati ents with essenti al hypertension, with a higher prevalence in uncontrolled than in controlled hypertension.
MAU was associated with high blood pressure levels, obesity and an increase in left ventricular mass.
Microalbuminuria refl ects a state of pathophysiologic vascular dysfuncti on that makes an individual suscepti ble to organ damage.
Further studies are needed to elucidate the underlying links between MAU and left ventricular structure.

TABLE 1 .
Characteristi cs of pati ents with and without MA Data are expressed as mean ± SD, BP = blood pressure