|Year : 2008 | Volume
| Issue : 3 | Page : 411-419
|Microalbuminuria in Patients With Essential Hypertension And its Relationship to Target Organ Damage: An Indian Experience
B Hitha, JM Pappachan, H Balachandran Pillai, P Sujathan, CD Ramakrishna, K Jayaprakash, KJ Raihanathul Misiriya
Kottayam Medical College, Kottayam, Kerala, India
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| Abstract|| |
Persistent microalbuminuria (MA) is the earliest indicator of chronic kidney disease (CKD) in patients with diabetes mellitus and hypertension. Patients with MA have high risk for target organ damage (TOD) resulting in stroke, retinopathy and adverse cardiovascular events. Though the prevalence of hypertension is high in India, the relationship between MA and TOD in hypertension is not well studied. To address this issue, this study was conducted at the Kottayam Medical College, Kerala, South India, between May 2005 and October 2006. The principal aim was to find out the prevalence of MA and its relationship to TOD in patients with essential hypertension. A total of 150 hypertensives without diabetes mellitus and/or other conditions causing MA were studied. Urine albumin-creatinine ratio (ACR) was assessed and MA was defined as albumin excretion between 30-300 mg/day. The relationship of MA with the duration, severity and previous treatment of hypertension, body mass index (BMI), lipid profile and TOD's like left ventricular hypertrophy (LVH), hypertensive retinopathy and stroke was assessed by univariate analysis. Forty patients (26.67%) were found to have MA of whom 24 were males and 16 were females. MA was significantly higher in those with longer duration and greater severity of hypertension (p <0.001 in each). Older age (p <0.001), adverse lipid profile (p <0.01) and higher BMI (p <0.04) were the other identifiable risk factors for MA. Gender and history of smoking did not pose higher risk for MA. Stroke (OR=3.8), echocardiography-proven LVH (OR=9.42) and hypertensive retinopathy (OR=9.7) were significantly higher in those with MA. In conclusion, the prevalence of MA in essential hypertension is high and patients with MA have high odds for developing TOD like stroke, LVH and hypertensive retinopathy. Early screening of hypertensives for MA and prompt treatment of positive cases might reduce the burden of CKD and cardiovascular disease in the community.
Keywords: Chronic kidney disease, Essential hypertension, Microalbuminuria, Target organ damage (TOD)
|How to cite this article:|
Hitha B, Pappachan J M, Pillai H B, Sujathan P, Ramakrishna C D, Jayaprakash K, Raihanathul Misiriya K J. Microalbuminuria in Patients With Essential Hypertension And its Relationship to Target Organ Damage: An Indian Experience. Saudi J Kidney Dis Transpl 2008;19:411-9
|How to cite this URL:|
Hitha B, Pappachan J M, Pillai H B, Sujathan P, Ramakrishna C D, Jayaprakash K, Raihanathul Misiriya K J. Microalbuminuria in Patients With Essential Hypertension And its Relationship to Target Organ Damage: An Indian Experience. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2022 Sep 30];19:411-9. Available from: https://www.sjkdt.org/text.asp?2008/19/3/411/40502
| Introduction|| |
Hypertension is a disease that affects about one billion individuals worldwide. It increases the risk for development of cerebral, cardiac, and renal events.  The majority of these patients have essential hypertension that can be defined as a rise in blood pressure (BP) of unknown cause Despite the widely recognized dangers related to uncontrolled hypertension, the disease remains inadequately treated in most patients, mainly due to its asymptomatic nature even when it progressively damages multiple organ systems. As a result, cardiovascular risk remains high among majority of the hypertensive patients.
Many patients with essential hypertension may present with overt or sub-clinical target organ damage (TOD) involving the heart, kidneys, central nervous system or retina at the time of their initial diagnosis. The cost effectiveness of BP reduction using drug therapy is greater in the presence of target organ abnormalities and/or co-morbidities. In this context, assessment of sub-clinical TOD has become the key element in evaluating hypertensive patients. Microalbuminuria (MA) is one of the earliest indications of kidney injury in patients with diabetes mellitus and hypertension and is associated with high incidence of cardiovascular morbidity. ,,,,,,,,
Recognition of MA stemmed from diabetes research four decades ago. The National Kidney Foundation of the United States defines MA as urine albumin excretion of approximately 30-300 mg/day in at least two out of three consecutive samples of nonketotic sterile urine. The association between MA and hypertension was described long time ago. A renewed interest in MA and essential hypertension occurred when several studies pointed out the importance of MA as a risk factor for renal and cardiovascular disease in patients with diabetes mellitus and hypertension. ,,, MA possibly reflects a state of increased renal endothelial permeability and is considered an early marker of diffuse endothelial dysfunction. ,,,
Though the prevalence of hypertension is reported to be about 25% in a recent community-based survey, 15 till now there is no data from India on the prevalence of MA and its association with TOD, among patients with essential hypertension. In this background, this study was conducted at the Kottayam Medical College, one of the biggest referral centers and a tertiary-care teaching hospital in South India, to detect the prevalence of MA, the probable risk factors for its development and the relationship of MA to TOD among patients with essential hypertension.
| Patients and Methods|| |
This cross-sectional cohort study was performed in patients with essential hypertension attending the medical outpatient clinic and those admitted to the medical wards at the Kottayam Medical College, between May 2005 and October 2006. Proven cases of secondary hypertension, pregnant women and those with diabetes mellitus, ischemic heart disease, renal disease, urinary tract infection, raised serum creatinine and macroproteinuria (albumin excretion more than 300 mg/24 hours), were excluded from the study cohort. Informed consent was obtained from each participant and the study was approved by the institutional review board.
Each participant was interviewed and examined in detail. Both patients undergoing treatment for hypertension, as well as newly detected hypertensives were included in the study. The BP of each participant was measured, using the auscultatory method with a standardized calibrated mercury column-type sphygmomanometer with an appropriate-sized cuff encircling at least 80% of the arm in the seated posture, with feet on the floor and arm supported at heart level (except when the patient had stroke and had been unable to sit, in which case, BP had been measured in the lying down posture). Two separate measurements were recorded at five-minutes intervals and the average of the two values was taken as the BP at that moment. Similar BP measurements were done on three occasions, a week apart, and a BP above 140/90 mm Hg was regarded as hypertension.
A detailed case record was prepared for each patient on a preformed study sheet. The important factors enquired in the history were: the duration of hypertension and of its treatment, history of smoking, cardiovascular symptoms like angina, palpitations, dyspnea and intermittent claudication, neurological symptoms like headache, seizures, transient ischemic attacks and previous stroke, and visual symptoms like blurring and/or dimness of vision. A detailed physical examination was performed on each patient that specifically emphasized on the assessment of the neurological status, cardiovascular status and optic fundus. Body mass index (BMI) was also recorded in all the ambulant patients.
Based on the duration of hypertension, the study population was divided into five groups:
a) Duration unknown,
b) Newly detected hypertensives,
c) Duration less than five years since diagnosis,
d) Duration 5-10 years since diagnosis and,
e) Duration more than 10 years since diagnosis.
Based on the findings of optic fundus examination (by direct ophthalmoscopy) the patients were divided into six groups:
b) Fundus not visualized because of hazy media,
c) Grade 1 hypertensive retinopathy
d) Grade 2 hypertensive retinopathy
e) Grade 3 hypertensive retinopathy and
f) Grade 4 hypertensive retinopathy
Special investigations that were done in the study cohort
In addition to the routine investigations like hematological and biochemical profile and work-up for secondary hypertension, the following special investigations were done in the study cohort.
a) Fasting lipid profile: according to the results obtained, the patients were grouped into those with favorable and those with unfavorable lipid profile based on the cardiovascular risk (the cardiovascular risk was assessed on the basis of ATP 3 guide-lines of the NCEP).
b) Electrocardiogram (ECG) to look for evidence of left ventricular hypertrophy (LVH). The Sokolow-Lyon index and Romhelt-Estes point score system were used to diagnose LVH by ECG criteria.
c) Chest radiography to look for cardiac enlargement.
d) Computed tomography (CT) of the brain for all patients admitted with a clinical diagnosis of stroke, transient ischemic attacks, seizures or altered sensorium.
e) Echocardiography: 2-D and M-mode echocardiograms were performed on each patient to assess the left ventricular (LV) geometry, LV function, chamber dimensions, valve morphologies and regional wall motion abnormallities. LVH was assessed on the basis of LV mass and relative wall thickness. LV mass more than 259 grams in men and 166 grams in women were considered abnormal; concentric LVH was considered to be present if the relative wall thickness was greater than 0.43 and/or the LV mass was increased.
f) Microalbuminuria was assessed by urine albumin-creatinine ratio (ACR) based on the recommendations of the National Kidney Foundation and the American Diabetic Association. The average ACR value from the three urine samples was determined. Urine albumin was estimated by turbidimetry. Five ml of first-voided, early morning sample of urine was used. The patients were asked to avoid exercise prior to the urine collection. In women, urine examinations were done during the non-menstrual phase of their cycles. ACR value between 30-300 mg/day was taken as MA.
| Statistical analysis|| |
Univariate analysis (chi square test) was used to determine the relationship between MA and other variables, and the results were expressed as p values and odds ratios.
| Results|| |
The data from 150 patients who satisfied the inclusion criteria during the study period were analyzed. Among them, 102 were outpatients and 48 were hospitalized patients. 101 patients were males and 49 were females. Forty hypertensives (26.67%) had MA of whom, 24 were males (23.7%) and 16 were females (32.7%), and there was no statistically significant difference in the risk for MA between the two sex groups (p = 0.248). Among the 84 smokers, 22 (27.2%) had MA and among the 66 non-smokers, 18 (27.3%) had MA, but these differences also were not significant on univariate analysis (p = 0.982).
The prevalence of MA among hypertensive patients increased steadily with their advancing age as shown in [Table - 1]. The prevalence of MA among hypertensive patients according to whether or not they were on (regular/ irregular) treatment is depicted in [Table - 2]. The prevalence of MA among hypertensive patients according to the duration of their disease is depicted in [Table - 3].
BMI could not be measured in 32 patients who were bed ridden because of stroke. Among the 138 patients whose BMI was measured, only one was obese (BMI 32 kg/m 2 ), none was very obese (BMI more than 40 kg/m 2 ), 14 were overweight (BMI 25 - 29.9 kg/m 2 ) and the remaining 103 had normal weight. MA was detected among four patients (28.6%) with overweight and 13 (12.6%) with normal weight and this difference was found to be statistically significant (p < 0.04). The obese patient did not have MA.
Among the 57 patients with unfavorable lipid profile, MA was detected in 22 (38.5%), whereas MA was detected in only 18 (19.3%) of the 93 patients with favorable lipid profile and the difference was found to be statistically significant (p < 0.01).
Of the hypertensives with various levels of BP, none of the 14 patients who had good control of BP with drug treatment (BP < 140/90) had MA. But, four (8.7%) among the 46 patients with systolic BP 140-159 and/or diastolic BP 90-99 mm Hg had MA and 36 (40%) among the 90 patients with BP more than 160/100 mm Hg had MA, and this difference was found to be statistically significant (p < 0.001).
Among the 127 patients in whom the optic fundus examination could be performed (in 23 cases optic fundi could not be visualized properly because of cataract), the relationship between MA and hypertensive retinopathy is shown in [Table - 4].
CT scans were performed on 49 patients with neurological symptoms and/or signs and 42 scans were abnormal (27 had cerebral infarcts and 15 had hemorrhages). Among the 150 patients, 44 (29.33%) showed LVH on echocardiography and 15 (10%) had LV dysfunction (12 had diastolic dysfunction and three had both systolic and diastolic dysfunction). Only 16 patients (10.67%) had ECG evidence of LVH.
The risk for various TOD's (stroke, LVH and hypertensive retinopathy) in hypertensives with MA is shown in [Table - 5].
| Discussion|| |
The overall prevalence of chronic kidney disease (CKD) in the United States is reported to have increased from 10 to 13% recently, and the major proportion of these patients have early CKD in the form of persistent MA.  There are no studies reported from India till date, that investtigated the prevalence of MA among patients with essential hypertension. The overall prevalence of MA in our study was 26.67% that is slightly higher than the prevalence of MA observed (23%) in the LIFE study.  Though the prevalence of chronic renal failure (defined by an elevation of serum creatinine more than 1.8 mg/ dl) was reported to be only 0.785% in a North Indian study,  these investigators did not consider the prevalence of early/ sub-clinical CKD in the form of MA. Hence, our observation on the high prevalence of MA in patients with essential hypertension, must alert the clinicians regarding the high prevalence of subclinical CKD in this part of the world, especially in view of the observations made by Mani MK from South India  on the preventive strategies for reduction of the burden of CKD by early detection and treatment of hypertension.
Though the relative risk for development of MA was found to be higher among men (men vs. women: 2.51 vs. 1.62) in the Gubbio Population Study,  the prevalence of MA was observed to be higher among females than in males in our study cohort, but the difference was not statistically significant. There was no statistically significant difference in the prevalence of MA between smokers and non-smokers in our study in contrast to the observation made by the others.  The small sample size of the present study might be one reason for this discrepancy. Advancing age was found to be a risk factor for higher prevalence of MA in our study also, as observed in other studies. , As expected, longer duration of hypertension was also associated with higher prevalence of MA in our cases.
Though not significant statistically, the low prevalence of MA among the hypertensives on regular anti-hypertensive treatment in the study cohort (the group under treatment showed a tendency towards lower risk of having MA; p = 0.07), points towards the role of drug therapy in hypertension in reducing the prevalence of CKD. Strict round the clock control of high BP is important in reducing the risk of MA in hypertensives because even isolated ambulatory hypertension is associated with higher risk for TOD. ,
High BMI among hypertensives is an important and well-known risk factor for the development of MA. ,,, Though the only obese patient in the study cohort did not have MA, significantly higher proportion of overweight individuals had MA when compared to the individuals with normal BMI. As observed in the Gubbio study,  an adverse lipid profile was found to be associated with higher prevalence of MA in our cohort as well.
MA had been reported to be three times more prevalent in patients with recent stroke,  and the risk for future stroke had been found to be high among patients with MA. , MA was more prevalent among patients with stroke (OR = 3.8) in the present study as well. Contrary to the observations made in the ETODH study,  we observed significant association between hypertensive retinopathy and MA (OR = 9.7). The prevalence of MA was also higher among those with higher grades of hypertensive retinopathy in this study. The reasons for this interesting observation may be investigated in future studies.
In patients with hypertension, LVH is one of the earliest TOD like MA,  and there is significant association between these two subtle TOD's as shown in many studies. ,,,, The prevalence of LVH found in our cohort was 29.33%, though the prevalence of LVH reported in other studies was higher. , But the higher odds for LVH in cases with MA (OR = 9.42) implies higher risk for cardiovascular events in the study population with hypertension. Early screening of hypertensive patients for MA and aggressive management of positive cases with drugs that decrease MA, might reduce their higher risks for progression to severe CKD, and adverse cardiovascular outcomes as shown in many studies. ,,,,,,
| Conclusions|| |
The prevalence of MA, an indicator of early CKD burden in the community, is about 27% among the patients with essential hypertension. Sex differences and smoking status do not pose any significant risk for the development of MA in essential hypertension. The patients with longer duration of hypertension, older age, higher BMI and adverse lipid profile are more prone to develop MA. Regular treatment of hypertension tends to reduce the development of MA. Higher grades of hypertensive retinopathy are associated with higher chance of development of MA. High prevalence of MA is seen in hypertensives presenting with stroke. Patients with essential hypertension and MA have high odds for developing TOD in the form of LVH, hypertensive retinopathy and stroke. Early screening of hypertensives for MA and prompt treatment of positive cases might reduce the disease burden related to severe CKD and cardiovascular events in the community.
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J M Pappachan
Senior lecturer in Medicine, Kottayam Medical College, Kottayam - 686008, Kerala
Source of Support: None, Conflict of Interest: None
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]
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