Profile of Non-Diabetic patients with Microalbuminuria in Acute Coronary Syndrome: A hospital based study

Background and Aims: Microalbuminuria (MA) (urinary albumin excretion of 30-299 mg/d in a 24 hours collection or 30-299 μg/mg creatinine in a spot collection) is well accepted marker of micro and macrovascular damage in patients with diabetes mellitus and is considered as a surrogate marker for endothelial dysfunction in diabetic and non-diabetic patients. This study has been undertaken to investigate the prevalence of microalbuminuria among non-diabetic Acute Coronary Syndrome (ACS) patients. Methods: : A hospital based cross-sectional study of 100 consecutive non-diabetic ACS patients was done. Traditional risk factors (like smoking, hypertension, dyslipidemia, obesity) of coronary artery disease were studied for the association with microalbuminuria in study subjects. Investigations were carried out in all the cases as per proforma and entered in the SPSS software for analysis. Results: The prevalence of microalbuminuria in non-diabetic ACS patients in the study was 73% which was statistically significant (p=0.04). A statistically significant higher prevalence of microalbuminuria was seen with different presentations of ACS; being highest (81.96%) in NSTEMI followed by STEMI (63.15%) and Unstable Angina (55%). It was found to be significant with the history of smoking (81.25%, p=0.013) and hypertension (82.25%, p=0.013). No significant association was found with age, body mass index (BMI) and dyslipidemia. A statistically significant higher prevalence of microalbuminuria was seen with increasing number of risk factors. Conclusion: There is increased prevalence of microalbuminuria in ACS patents. MA was associated with statistically higher number of cases with history of smoking and hypertension and presence of increasing number of risk factors.


Introduction
Microalbuminuria (MA) is defined as increased urinary albumin excretion of 30-299 mg/d in a 24 hours collection or 30-299 µg/mg creatinine in a spot collection 1 .
Evidence has shown an early increase of urinary albumin in acute myocardial infarction is a strong independent predictor of long-term adverse clinical outcome and Albumin Creatinine Ratio (ACR) improved clinical prediction over and above baseline traditional multivariable risk models 2 . The study on "Relationship between MA @ Nepalese Heart Journal. Nepalese Heart Journal retain copyright and works is simultaneously licensed under Creative Commons Attribution License CC -By 4.0 that allows others to share the work with an acknowledge of the work's authorship and initial publication in this journal and the Presence and Extent of Coronary Atherosclerosis" found MA to be an independent predictor for the presence and severity of CAD. They concluded a strong relationship between MA and the severity of CAD 3 . Some studies show patients with higher proteinuria are at risk of developing higher degrees of ACS with adverse outcomes 3,4 .
There is a study regarding outcomes in ACS patients in Nepal taking in consideration of ACS patients only (including all the risk factors) 5  The diagnostic criteria used for each were as under: 1) ST Elevation Myocardial Infarction (STEMI): Cases fulfilling two of the following three criteria-a) History of prolonged chest discomfort or angina equivalent (30 minutes). b) ST-elevation 1mm or more in two consecutive leads or new onset Left Bundle Branch Block (LBBB). c) Presence of elevated cardiac biomarkers. 2) Non ST Elevation Myocardial Infarction (NSTEMI): Severe chest discomfort having at least one of three features along with evidence of myocardial necrosis as reflected by abnormally elevated levels of biomarkers of cardiac necrosis. i) Occurring at rest (or with minimal exertion), lasting for > 10 minutes ii) Recent onset (i.e. within the prior 2 weeks) iii) Occurring with crescendo pattern (i.e. distinctly more severe, prolonged, or frequent than previous episodes. 3) Unstable Angina (UA): Angina pectoris or equivalent ischemic discomfort with at least one of three features: i) Occurring at rest (or with minimal exertion), lasting for > 10 minutes ii) Recent onset (i.e. within the prior 2 weeks) iii) Occurring with crescendo pattern (i.e. distinctly more severe, prolonged, or frequent than previous episodes. The following cases were excluded: 1. Known cases of diabetes mellitus. Cases showing random blood sugar ≥200mg/dl. 3. MA >300mg µg/mg creatinine. 4. Serum Creatinine >1.5mg/dl. 5. Patients showing pyuria with urine microscopy showing ≥8WBC/hpf. Patients with history of preexisting congestive cardiac failure. Urine examination was carried out for all patients. a) Routine and microscopy b) MA by Nyocard kit test. The patients were explained about the procedure of urine specimen collection. Urine spot test was opted for assessment of MA for feasibility. Early morning midstream specimen was collected after washing the penile area in males, and perineal area in females. All urine specimens were obtained aseptically in well labeled screw capped universal containers and were promptly transported to laboratory for routine and microscopy examination and MA estimation.
The data was entered in excel sheet and analyzed using SPSS software version 16. Percentage, mean value were calculated and Pearson's correlation coefficient, chi square test, t-tests, odds ratio etc were calculated wherever required and p values were considered significant at a predetermined alpha level of 5%.
The prevalence of MA was highest in NSTEMI group being 81.96%. The corresponding figures in STEMI and Unstable Angina were 63.15% and 55% respectively. The difference was statistically significant (p=0.035).

Urine
No of patients  endothelial dysfunction (ED) and its presence is considered as coronary artery disease equivalent. Hence to minimize confounding bias, we wanted to exclude diabetes (however other risk factors like hypertension and dyslipidemia are included). So, this study aims to find an association of MA in non-diabetic ACS patients admitted in Manipal Teaching Hospital which may represent patients of western region of Nepal being a referral center for ACS.

Discussion
The overall prevalence of micro-albuminuria in non-diabetic ACS in this study was 73% which was statistically significant (p=0.04). The studies done outside also show similar findings ranging from 58-92% [6][7][8][9][10] . In the study done by F Aziz et al found prevalence of MA to be 56.5% in angiographically proved severe CAD (luminal narrowing > 70%) 11 , Similarly, in the study done by Silva et al on prevalence of MA in 39 patients with angiographically confirmed severe lesion (stenosis > 70%) in at least one coronary artery found to be 33% which was statistically significant 12 . The results of above studies cannot be matched with our study due to different inclusion criteria but nevertheless they confirm the fact that MA is present in statistically significant number of cases in coronary artery disease.
This study showed no difference in MA between different sexes (p = 0.202). Few studies 13,14 also show similar results but a case control study done by Basu et al found a statistically significant higher numbers of males (83.33%) as compared to females (40%) 6 . In the study done by Silva et al on determination of MA in hypertensive patients and in patients with coronary artery disease found prevalence of MA was 23% in the age group 56 years and above and 5% in age group 55 years and below which was statistically significant 12 .
The prevalence of MA was highest in NSTEMI group being 81.96%. The corresponding figures in STEMI and Unstable Angina were 63.15%and 55% respectively. The difference was statistically significant (p= 0.035). Zeeshan A, Ahmad Z, Tahir GA, Yaqoob Y in their study on acute coronary syndrome titled MA as atherosclerotic risk factors and its association found MA in 20.4% cases of STEMI. The corresponding figures in NSTEMI and Unstable angina were 21.3% and 25.3% respectively 15 . In contrast, Abdul Ghaffar Memon and Mubashir Kolachi in their study on relationship of MA in non-diabetic and non-hypertensive patients with acute myocardial infarction done in Hyderabad, Pakistan found MA in 53.17% STEMI and15.8% NSTEMI 8 .
Out of 64 patients with the history smoking in our series, MA was present in 52 (81.25%) while out of 36 nonsmokers, MA was found in 21 (58.33%) patients. The difference was statistically significant (p = 0.013). Basu A et al in their study of 50 non diabetic and non-hypertensive patients of ACS with similar inclusion criteria as our study found MA was present in 92% (23 out of 25) of patients with smoking while out of 25 nonsmokers, MA was found in 10 (40%) of patients .The difference was statistically significant (p < 0.001) 6 . However Bhalabhi Vaishali and Ghanekar Gayatri in their study of correlation of MA and multiple risk factors in acute coronary syndrome found MA in 50% (6 out of 12) of patients with smoking which was not statistically significant (p > 0.05). However cases of diabetes mellitus were also included in their study 7 . Since association of smoking and MA has long been known, further large scale studies are required to determine its association in patients with acute coronary syndrome.
In our study, out of 62 hypertensive patients in our series, MA was present in 51 (82.25%) of the cases while corresponding figures in 38 normotensive patients was 22 (57.89%). The difference was statistically significant (p = 0.013). Bhalabhi Vaishali and Ghanekar Gayatri in their study of correlation of microalbuminuria and multiple risk factors in acute coronary syndrome found microalbuminuria to be present in 8.82% among hypertensive cases which was not statistically significant (p > 0.05). Cases of diabetes mellitus were also included in their study 7

Conclusion
Overall prevalence of microalbuminuria in non-diabetic ACS patients in our study was 73%.There is no difference in prevalence of microalbuminuria between males and females. Highest prevalence of microalbuminuria was seen in NSTEMI patients. Microalbuminuria was associated with statistically higher number of cases with history of smoking and hypertension and with increasing number of risk factors present.

Limitations and recommendations
Our study consisted of 100 patients only and the results of our study need to be substantiated with the results of prospective larger clinical studies with matching clinical criteria.