International Journal of Advances in Medicine

Jamra Y et al. Int J Adv Med. 2017 Jun;4(3):778-782

http://www.ijmedicine.com

pISSN 2349-3925 | eISSN 2349-3933

A prospective study on urinary microalbuminuria as surrogate marker of vascular endothelial dysfunction, in patients of ischemic stroke

Yogendra Jamra*, Dharmendra Jhawar, Rajneesh Patidhar


Department of Medicine, M. G. M. Medical College, Indore, Madhya Pradesh, India

Received: 18 March 2017

Accepted: 18 April 2017

*Correspondence:

Dr. Yogendra Jamra,

E-mail: drysjamra@gmail.com

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Presence of overt proteinuria has been independently linked to greater stroke risk. The objectives of this study were to determine the relationship between the for ischemic stroke and albuminurea as a marker for vascular events. Microalbuminuria, is an early marker of both kidney disease and endothelial dysfunction, may be associated with global vascular risk, but the nature and relationship between microalbuminuria and incident ischemic stroke has not been clearly defined. The purpose of this study was to assess the association of microalbuminuria and ischemic stroke.

Methods: Study enrolled 150 admitted patients of acute ischemic stroke. The patients were assessed by questionnaire, microalbuminuria, creatinine clearance after detailed history taking and thorough clinical examination.

Results: The combined common risk factors were HTN (80%), diabetes (33%) and smoking (53%). The hypertensive patients had 8 times higher risk of microalbuminuria as compared to normotensive patients (95% 1.8-31.0 p<0.05). Among diabetes patients had risk of microalbuminuria 30 times higher compared to euglycemic patients (95% CL 9.6-78.8 p<0.01). The smoker patients had 8 times risk of microalbuminuria (CL 95%-1.2-22.8 p<0.16). However, the patients who had dyslipidemia had risk of microalbuminuria 1.07 times who have normal lipid level, but it was statistically insignificance (98% CL 0.8-4.1 p>0.05). The 38 patients out of 46 patients who had microalbuminuria has high normal serum creatinine with creatinine clearance (45-59 mL/min/1.73 m2. (82% versus. 4.4% 30.44 mL/min/173m2). The risk of microalbuminuria was higher in patients who had high normal serum creatinine (1.4 mg/dL) with creatinine clearance of 45-59 mL/min/1.73 m2 versus normal serum creatinine 0.8 mg/dL.

Conclusions: The finding of the study, show the microalbuminuria is an independent risk factor for vascular endothelial dysfunction, in patient of diabetes early renal dysfunction and HTN, extrapolating the vascular event (ischemic stroke).

Keywords: Creatinine clearance, Microalbuminuria

INTRODUCTION

Presence of overt proteinuria has been independently linked to greater stroke risk furthermore, emerging data suggest that microalbuminuria may boost stroke risk but the full extent of the relationship between urinary albumin excretion and stroke has not been established.1,2 Microalbuminuria is considered as a marker of vascular endothelial damage, the latter being the underlying cause of vascular diseases microalbuminuria may be related to vascular damage by several biological pathways like renal dysfunction, transvascular escape of albumin, endothelial dysfunction and inflammation microalbuminuria as an independent risk factor for ischemic stroke has been widely published, microalbuminuria has been positively correlate with carotid-intimal thickness, a well-recognized marker of cerebrovascular disease increasing the awareness of microalbuminuria as an early prognostic indicator of stroke risk.3-10

The goal of this study is designed, therefore, to determine its relationship to risk factor for stroke.

METHODS

A cross sectional observation study was carried in Department of Medicine, M. G. M. Medical College, Indore, Madhya Pradesh, India during period of April 2015-July 2016. The study was approved by Ethics Committee of M. G. M. Medical College, Indore, Madhya Pradesh, India. The study is performed on 150 patients admitted in medical I. C. U. under department of medicine.

Eligibility criteria

Ischemic stroke survivor who have at least two traditional risk factor like DM / HTN / cigarette smoking etc.

Exclusion criteria

Clinical feature similar to stroke like: subarachnoid hemorrhage, Subdural hematoma, epilepsy, previous stroke, epilepsy, T.I.A., patient with overt albuminuria (>300 mg/day), UTI, CCF, pregnant female, bed-ridden patient for more than 2 weeks, septicemia and infection. The patients were assessed by questionnaire, clinical examination, routine investigation including HbA1C, urine for microalbumin, CT / MRI brain.

Criteria for diagnosis of DM

  • • FBS>126 mg/dL
  • • HbA1C > 6.5%
  • • 2-hour plasma glucose 200 mg/dL after oral glucose tolerance test.

Assessment for microalbuminuria

Microalbuminuria was tested by Micral Test (Roche Diagnostic) manufacture limited. The test was dependent on color reaction and was mediated by an antibody bound enzyme. This method has shown good correlation with radioimmunoassay and can be readily used for screening. A reading more than 30 mg/dL was considered as positive.

Definition of microalbuminuria

Refer to urinary albumin excretion above 30 mg/dL and less than 300 mg/dL.

Statistical analysis

The discrete data were assessed in number and percent. Chi-square test was used for determining the relation between HTN, DM, dyslipidemia, smoking and microalbuminuria p value (2 sided) <0.0005 represent statistical significance.

Statistical significance assesses by SPSS version 10.

Spearman-Row-non-parametric correlation was applied between study parameter.

RESULTS

A total of 150 patients of ischemic stroke (median age 55 years) who were enrolled in prospective study. The commonest age group of ischemic strokes (44%) is 51-60 years of age (Table 1).

Table 1: Age wise distribution of patients.
Table reproduced from source PDF page 2

According to our study, we have 150 patients (mean age 55 year) diagnosed with ischemic stroke, confirmed by Computed Tomography, who were admitted to the intensive care unit within 24 hours after the onset of symptom (Table 2).

Table 2: Classification of patients according to glycemic status in relation to stroke.
Table reproduced from source PDF page 2
Table 3: Risk factor for stroke.
Table reproduced from source PDF page 2

Out of 150 patients, 66 cases (44%) of stroke occur in age group of 51-60 years, another 36 cases 24% occurred in age group 61-70 years. This show commonest age group is 51-60 years (Table 3). For ischemic stroke observed in our study. We had 120 patients of HTN, microalbuminuria is present in 44 patients (36%), the HTN patients had 8 times higher risk of MA (ODD Ratio 8.2; 0.95% C.L.; (1.8-31.9), p value 0.018 (significant).

Table 4: Relationship of hypertension / diabetes / dyslipidemia / smoking with microalbuminuria.
Table reproduced from source PDF page 3

In this study, diabetes mellitus was on important risk factor for microalbuminuria, (Table 4) microalbuminuria is observed in 40 (33%) patients of DM as compared to 120 patients of euglycemic (ODD ratio 30:95% C.L. (9.6-78.8), p value 0.001 (significant). Smoking is also a contributing factor for microalbuminuria. We observed microalbuminuria in 24 (35%) patients out of 67 smoker patients with (ODD Ratio 7.0:95% C.L. (1.2-22.8), p value 0.016 (significant).

The patient who had dyslipidemia, had lower incidence (non-significant) contribution for microalbuminuria. We have observed 90 patients of dyslipidemia, 20 patients had microalbuminuria, (ODD Ratio 1.07: 95% C.L. (0.8-4.0) p value <0.175 (non-significant).

Table 5: Relationship of creatinine clearance and microalbuminuria.
Table reproduced from source PDF page 3

CrCL Cock-Croft-Gault Equation

140-age x body weight

CrCL (mL/mint) = ------------------------

72 x Pcr (mg/dL)

Microalbuminuria was present in 38 patients who had high normal serum creatinine (1.2-1.4 mg/dL) with creatinine clearance of 45-59 mL/mint/1.73m2, only 2 patients out of 150 patients had macroalbuminurea with serum creatinine (1.4-1.6 mg%) cr.cl-30-44 mL/mint/1.73m2 (Table 5).

DISCUSSION

According to our study, risk factor for ischemic stroke are HTN, DM and smoking had microalbumunurea 36%, 60%, 35% respectively. The patients who had DM have 30 times more risk of microalbuminuria than general population. The 38 patients who had creatinine clearance (CrCl) between 45-59 /mL/mint/1.73m2 had microalbuminuria of more than 30 mg/dL. It is an independent relationship between creatinine clearance and microalbumin in newly diagnosed hypertensive and type II diabetes mellitus.11

In present study creatinine clearance has shown slight positive correlation with microalbuminuria. The serum creatinine was in high normal range with creatinine clearance of 45-59 /mL/mint/1.73m2. Hence, even minor decrement in GFR result, presence of microalbuminuria, is now recognized risk factor for cardiovascular disease.12

Smoking was independently associated with microalbuminuria and its prevalence is almost double in smoker than non-smoker with primary HTN.13,14 The HOPE study, document smoking is an independent determinant of microalbuminuria in DM and non-DM patients with high cardiovascular profile.15

Although previous studies had shown proteinuria as an independent predictor of stroke outcome in general population, none have examined the possible association between microalbuminuria and incident of stroke.16,17

Microalbuminuria is independently associated with carotid artery intima-media thickness in non-DM individual in insulin resistance and atherosclerosis study, USA.18 The Epic Norfolk study is the 1st report evaluating the prospective relationship between microalbumin and fatal and non-fatal cerebrovascular accidents in general population.19

Still observation studies cannot prove causality and mechanistically it is unclear how albuminuria would directly cause stroke. It is more likely that albuminuria and stroke closely share similar underlying pathophysiological process (e.g. generalized endothelial dysfunction and enhance the penetration of lipoprotein into arterial wall, and albuminuria and cerebrovascular diseases are not casually related but rather reflect common determinants.20-22

CONCLUSION

Microalbuminuria can serve as useful risk marker for generalized vascular endothelial dysfunction and early renal impairment. Test for urine microalbumin is simple and relatively cheap, for assessing underlying vascular endothelial dysfunction and extrapolating vascular event.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the institutional ethics committee

REFERENCES

  1. 1. Ninomiya T, Perkovic V, Verdon C, Barzi F, Cass A, Gallogher M, et al. Proteinuria and stroke; meta-analysis of cohort studies. Am J Kidney Dis. 2009:53:417-25.
  2. 2. Ovbiagale B. Microalbuminuria; risk factor and potential therapeutic target for stroke. J Neuro Sci. 2008:271:21-8.
  3. 3. Halini JM, Farhan A, Balkau B, Novak M, Wilpart E, Tichet J, et al. Is microalbuminuria an integrated risk marker for cardiovascular disease and insulin resistance in both men and women. J Cardio Risk. 2001:8:139-46.
  4. 4. Mathur PC, Punekar P, Muralidharan R. Microalbuminuria in non-diabetic acute ischemic stroke an Indian perspective. Ann Ind Acad Neurol. 2005:8:237-42.
  5. 5. Nakayoma T, Date C, Yokoyama T, Yashika N, Yamoguchi M, Tanaka H. A 55 year follow-up study of stroke in Japanese provincial city; the Shibata study. Stroke. 1997:28:45-52.
  6. 6. Mykkanen L, Zaccaro DJ, Leary DH, Howard G, Robbin DC, Haffner SM. Microalbuminuria and carotid intima-media thickness in non-diabetic and NIDDM subject; The insulin resistance atherosclerosis study (IRAS). Stroke. 1997:28:1710-6.
  7. 7. Montalecost G, Colleat J. Preserving cardiac function in the hypertensive patients why renal parameter hold the key. Euro Heart J. 2005:26:2616-22.
  8. 8. Donnelly R, Yeung JM, Manning G. Microalbuminuria: a common, independent cardiovascular risk factor, especially but not exclusively in type II diabetes. J Hyper Sup. 2003:21(1);57-62.
  9. 9. Naidoo DP. The link between microalbuminuria endothelial dysfunction and cardiovascular disease in diabetes. Cardio J South Africa. 2002:13:194-9.
  10. 10. Valmadrid CT, Klein K, Mols F, Klein BEK. The risk of cardiovascular disease mortality associated with microalbuminuria and cross proteinuria in person with older onset diabetes mellitus. Arch Intern Med. 2000:160:1093-100.
  11. 11. Afsar B, Elasrer B. The independent relationship between creatinine clearance, microalbuminuria and circadian blood pressure in newly diagnosed essential hypertension and type II diabetic patients. J Diabet Comp. 2012;26(6):531-5.
  12. 12. Bargman JM, Skorecki K. Harrison: Principle of internal medicine. 2015;2:1812-3.
  13. 13. Hiltege HL, Janseen WM, De Jong P. Microalbumuria is common also in non-diabetic, non-hypertensive population and independent indicator of cardiovascular risk factor and cardiovascular mortality. J Intern Med. 2001;249:519-26.
  14. 14. Horner D, Hisher D, Ritz E. Albuminuria in normotensive and hypertensive individual attending office of general practitioner. J HTN. 1996;14:655-60.
  15. 15. Gerstein HC, Man JF, Pogue J, Young J, Dinnen SF, Yusuf S. Prevalence and determinant of microalbuminuria in high risk diabetes and non-DM patients in heart outcome preventive evaluation study. The HOPE study investigator. Diabet Care. 2000;23 (sup 2):B35-B39.
  16. 16. Nakayama T, Dale C, Yokoyama T, Yoshika N, Yamaguchi M, Tanaka H. 15.5 year follow-up: study of stroke in Japanese provincial study. The Sobita Stroke. 1997;28;45-52.
  17. 17. Miettien H, Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso. Proteinuria predict vascular diseases event in non-diabetic and non-insulin diabetic subject. Stroke. 1996;27;2033-9.
  18. 18. Nent MYKK, Zaccaro DJ, O’Leary DH, Howard G, Robbin GC, Haffner SM. Microalbumuria and carotid artery intima media thickness in non-DM and NIDDM subjects; The insulin resistance atherosclerosis study (IRAS). Stroke. 1997;28;1710-6.
  19. 19. Yu Yun MF, Khaw KT, Luben R, Welch A, Bingham S, Day WE, et al. Microalbumuria and stroke in British population the Europeanprospective. Investigation into cancer in Norfolk (Epic-Norfolk) population study. J Intern Med. 2004;255:247-56.
  20. 20. Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease effect on cardiovascular system. Circulat. 2007;116;85-97.
  21. 21. Roguer J, Segura T, Serena J, Castillo J. Endothelial dysfunction, vascular diseases and stroke; the ARTICO study. Cerebrovascular Dis. 2009;8;27(sup 1);25-37.
  22. 22. Deckert T, Feldt-Rasmussen B, Borch-Johnson K, Jenson T, Envoldsen K. Albuminuria reflect wide spread vascular damage; The steno hypothesis. Diabetol. 1989;32:219-26.