ABSTRACT

CORRESPONDING AUTHOR:
Dr. Shrawan Kumar,
House No. 303, Staff Quarter-1,
Rama Medical College, Mandhana,
Kanpur, Uttar Pradesh – 209217.
Email- drshrawanknp@gmail.com

ABSTRACT: INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD), comprising a spectrum of condition ranging from pure steatosis to steatohepatitis and cirrhosis. Increasing the recognition of the importance of NAFLD and its strong relationship with metabolic syndrome has stimulated interest in the possible role of NAFLD in the development of cardiovascular disease. AIMS AND OBJECTIVE: To study the relationship between 1.Cardiovascular diseases and diabetic patients having non-alcoholic fatty liver.2.Cardiovascular diseases in obese and hypertensive patients having non-alcoholic fatty liver. MATERIALS AND METHODS: The study was conducted on 50 diagnosed patients of NAFLD, with objective to identifying the association of various cardiovascular risk factor associated with it.The study was design to study the association or co-relation between NAFLD to various cardiovascular risk factor, diagnosed by standard laboratory, imaging and by physical measurement. We used the standard value of p and chi square for establishing statistically significant association between multiple variables in our study. RESULTS: In our study out of 50 patients, 30 male and 20 female patients, 05 males and 03 females in group A, 20 males and 13 females in group B and 05 male and 04 female patients in group C, the p value (≤0.05) and chi square value (=15). 50 patients of NAFLD were randomized into two groups, group A (NAFLD with obesity, p value 0.0048, chi value of 10.667) and group B (NAFLD without obesity p = (NA) and chi square value = (NA). Patients of NAFLD were randomized into two groups, group A (NAFLD with diabetes, p value 0.0002 and chi value of 16.8) and group B (NAFLD without diabetes, p value = (NA) and chi square value =NA).Patients of NAFLD were randomized into two groups, group A (NAFLD with Hypertension p value 0.0009 and chi value of 14) and group B (NAFLD without Hypertension disease p value is (NA) and chi square value is (NA). CONCLUSION: We hereby conclude from the present study that NAFLD is not only the disease of liver; rather it has statistically high significant association with cardiovascular disease (ischemic heart disease), obesity, diabetes, older age group, male sex, metabolic syndrome etc.

KEYWORDS: NAFLD, FATTY LIVER, CARDIOVASCULAR RISK FACTORS

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD), comprising a spectrum of condition ranging from pure steatosis to steatohepatitis and cirrhosis. Increasing the recognition of the importance of NAFLD and its strong relationship with metabolic syndrome has stimulated interest in the possible role of NAFLD in the development of cardiovascular disease. The possible molecular mediator linking NAFLD and CVD include the release of pro-atherogenic factors from the liver (C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 and other inflammatory cytokines) as well as contribution of NAFLD per se to whole-body insulin resistance and atherogenic dyslipidemia in turn favoring CVD progression. The clinical impact of NAFLD on CVD risk deserves particular attention in view of implication for screening and surveillance strategies in the growing number of patients with NAFLD. Liver is the central for the production of classical biomarkers of inflammation and endothelial dysfunction, the secretion of which partly depends on the factor that are unregulated in the presence of insulin resistance and metabolic syndrome: IL-6 and TNF are the major stimuli responsible for increase hepatic production of C-reactive protein(CRP), fibrinogen and other acute phase protein. The fibrinogen and CRP levels, which are known CVD risk factor, are increased in NAFLD patient.

AIMS AND OBJECTIVE:

1. 1.      To study the relationship, if any, between cardiovascular diseases in diabetic patients having non-alcoholic fatty liver.
2. 2.      To study the relationship, if any, between cardiovascular diseases in obese and hypertensive patients having non-alcoholic fatty liver.

MATERIAL AND METHODS: The study was conducted on 50 diagnosed patients of non alcoholic fatty liver disease, with objective to identifying the association of various cardiovascular (ischemic heart disease) risk factor associated with it, like diabetes, hypertension, obesity, dyslipidemia etc. The study was design to study the association or co-relation between non alcoholic fatty liver disease to various cardiovascular risk factor, diagnosed by standard laboratory, imaging and by physical measurement. We used the standard value of p and chi square for establishing statistically significant association between multiple variables in our study.

Inclusion criteria:

• Adult above 30 years of age.

Exclusion criteria:

• Person not willing to take participation.
• Adult with increased alcohol intake.
• Patients having any congenital heart disease.
• Patients on the treatment of diabetics.
• Patients on hypolipidemic drugs.
• Smokers.

Defining criteria for the diabetes, hypertension, obesity (BMI), waist circumference and metabolic syndrome.

1. 1.      Obesity diagnosis and classification:

BMI is calculated by dividing the subject’s mass by the square of his or her height, typically expressed either in metric or US “customary” units.

BMI < 18.5 → normal weight,

BMI = 25.0-29.9 → overweight,

BMI = 30.0-34.9 → Class I obesity,

BMI = 35.0-39.9 → Class II obesity,

BMI ≥ 40.0 → Class III obesity.

1. 2.      Criteria for defining diabetes: (WHO criteria)

Fasting plasma glucose level ≥ 7.0mmol/l (126 mg/dl).

• Plasma glucose ≥ 11.1 mmol/l (200mg/dl) two hours after a 75g oral glucose load as in a glucose tolerance test.
• Symptoms of hyperglycemia and casual plasma glucose ≥ 11.1 mmol/l (200 mg/dl)
• Glycated haemoglobin (HbA1C) ≥ 6.5%

1. 3.      Dyslipidemia:

• Triglycerides level 150 mg/dl (1.7mmol/l) or greater.
• HDL-Cholesterol < 40 mg/dl (< 1.04 mmol/l) in men and <50 mg/dl (< 1.29 mmol/l) in women.

1. 4.      Central obesity (measured by BMI):

• Waist circumference > 102 cm (40 inches) in men
• Waist circumference > 88 cm (35 inches) in women
• Central obesity is defined as waist circumference but can be assumed if BMI > 30kg/m² with ethnicity specific values.

1. 5.      Metabolic syndrome:

• WHO criteria (1988).
• Insulin resistance.
• Abdominal obesity (waist-to-hip ratio > 0.9 in men or 0.85 in women, or BMI > 30kg/ m²).
• Triglycerides 150 mg/dl (1.7 mmol/l) or greater, and/or HDL-Cholesterol < 40 mg/dl (1.04 mmol/l) in men and < 50 mg/dl (< 1.29 mmol/l) in women.
• Blood pressure ≥ 140/90 mm Hg.

RESULTS AND OBSERVATION: The study was conducted on 50 diagnosed patients of non alcoholic fatty liver disease, with objective to identifying the association of various cardiovascular (ischemic heart disease) risk factor associated with it, like diabetes, hypertension, obesity, dyslipidemia etc.

The patient was divided in to three age groups,

Group A → 30-49 years

Group B → 50-69 years

Group C → 70-90 years

TABLE – 1.  Distribution of age and sex in non alcoholic fatty liver disease

This test shows very significant association of non alcoholic fatty liver disease with male sex.

TABLE – 2.  Association of ischemic heart disease with diabetes in NAFLD

Test is statistically non significant.

TABLE – 3.  Relationship between cardiovascular (ischemic) diseases with hypertensive in NAFLD

On applying FISHER Z TEST of proportional analysis, GROUP “A” of age between 50-69 and 70-90 has significant association with NAFLD.

TABLE – 4.  Showing association of ischemic heart disease with hypertension and obesity in non alcoholic fatty liver disease

The test result is not significant due to small sample size.

TABLE – 5.  Cardio-vascular disease (ischemic heart disease): association with or without metabolic syndrome in non alcoholic fatty liver disease.

The test result shows GROUP A is not significant and GROUP B is significant at P VALUE < 0.25 which is statistically significant for small sample size.

TABLE – 6.  Association of obesity in patients of non alcoholic fatty liver disease.

The test result shows significant association of obesity with non alcoholic fatty liver disease.

TABLE – 7.  Association of diabetes with non alcoholic fatty liver disease

Test result shows significant association of diabetes with non alcoholic fatty liver disease.

TABLE – 8.  Association of cardiovascular disease (ischemic heart disease) with non alcoholic fatty liver disease.

Test result shows that there is no relation of obesity with ischemic heart in non alcoholic fatty liver disease.

TABLE – 9.  Association of hypertension with non alcoholic fatty liver disease.

Test result shows there is significant association of hypertension with non alcoholic fatty liver disease.

TABLE – 10.  Association of metabolic syndrome with non alcoholic fatty liver disease.

The test result shows metabolic syndrome has significant association with non alcoholic fatty liver disease. p<0.25 may be significant for small sample size.

TABLE – 11.  Comparison of association of diabetes and metabolic syndrome in non alcoholic fatty liver disease.

The above result shows that diabetes has greater association with non alcoholic fatty liver disease than metabolic syndrome has.

DISCUSSION: The study was concluded on 50 diagnosed patient of non alcoholic fatty liver disease mainly by USG. Patient was divided into three group according to age, group a (30-49), group b (50-69) and group c (70-90). The study was design to study the association or co-relation between non alcoholic fatty liver disease to various cardiovascular risk factor, diagnosed by standard laboratory, imaging and by physical measurement. We used the standard value of p and chi square for establishing statistically significant association between multiple variables in our study.

Distribution of age and sex in non alcoholic fatty liver disease: In our study on 50 patients, divided into three groups, group a, group b and group c; there were a total of 30 male and 20 female patients, 05 males and 03 females in group a, 20 males and 13 females in group b and 05 male and 04 female patients in group c. the p value (≤0.05) and chi square value (=15) of the study signify the statistically significant association of male sex with NAFLD.

Association of cardiovascular disease (ischemic heart disease) with diabetes in non alcoholic fatty liver disease: In this study on 50 NAFLD patients, 15 patients (30%) were found to have both ischemic heart disease and diabetes. The chi square value (=2.8), and p value (<0.25) of the test indicate no statistically significant association but p value (<0.25) indicate 75% significant association which become significant in small sample size. Similar results were found with study of Targhar G, Bertolini L et al (2007)

Association of obesity in non alcoholic fatty liver disease: In this study 50 patient of non alcoholic fatty liver disease were randomized into two groups, group A (NAFLD with obesity) and group B (NAFLD without obesity). Further these were divided into three age groups. On analysis group A has p value 0.0048 and chi value of 10.667, group B has p value = (NA) and chi square value = (NA). On comparative study between group A and B, group A has statistically significant association and similar results were also observed by study of Agarwal AK et al (2011).

Association of diabetes in non alcoholic fatty liver disease: In this study 50 patients of non alcoholic fatty liver disease were randomized into two groups, group A (NAFLD with diabetes) and group B (NAFLD without diabetes). These further divided into three age groups. On analysis group A has p value 0.0002 and chi value of 16.8, group B has p value = (NA) and chi square value = (NA). On comparative study between group A and B, group A is statistically significant, similar results were also observed by Mantovani A et al (2012) in their study.

Association of hypertension with non alcoholic fatty liver disease: In this study, 50 patients of non alcoholic fatty liver disease were randomized into two groups, group A (NAFLD with Hypertension) and group B (NAFLD without Hypertension disease). These further divided into three age groups. On analysis, group A has p value 0.0009 and chi value of 14. While in group B, the p value is (NA) and chi square value is (NA) and similar results were also found with study of Catena C et al (2012).

Association of metabolic syndrome with non alcoholic fatty liver disease: In this study, 50 patients of non alcoholic fatty liver disease were randomized into two groups, group A (NAFLD with metabolic syndrome) and group B (NAFLD without metabolic syndrome). These further divided into three age groups. On analysis, group A has p value 0.0302 and chi square value is 07, while in group B, the p value is (NA) and chi square value is (NA). This was supported by Liu CJ (2012).

Comparison of association of diabetes and metabolic syndrome in non alcoholic fatty liver disease: In this study, 50 NAFLD patients were randomized into two groups; Group A (NAFLD patients with diabetes mellitus) and Group B (NAFLD patients with metabolic syndrome). Comparative study was done to find the association between them. Test suggests that diabetes has a greater association with non alcoholic fatty liver disease than does metabolic syndrome have. Association of diabetic with non alcoholic fatty liver disease increases as age advances. Similar results were also observed by Paloma AV et al (2009).

CONCLUSION: We hereby conclude from the present study that NAFLD is not only the disease of liver; rather it has statistically high significant association with cardiovascular disease (ischemic heart disease), obesity, diabetes, older age group, male sex, metabolic syndrome etc. So every patient suspected or diagnosed to have non alcoholic fatty liver disease should be investigated for above mentioned disorder for comprehensive management.

BIBLIOGRAPHY:

1. Agarwal AK, jain V, Singla S, Baruah BP, Arya V, Yadav R,Singh VP: Prevalence of non-alcoholic fatty liver disease and its correlation with coronary risk factors in patients wih type-2 diabetes. J Assoc Physicians India. 2011 Jun; 59:351-4.
2. Alkhouri N, Carter-Kent C, Elias M, Feldstein AE: Atherogenic dyslipidemia and cardiovascular risk in children with non alcoholic fatty liver disease. Clin lipidol.2011 Jun 1; 6(3):305-314.
3. Ampuero J, Romero-Gomez M: Influence of non-alcoholic fatty liver disease on cardiovascular disease. Gastroenterol Hepatol.2012 Oct; 35(8):585-93.
4. Arslan N, Makay B: Mean platelet volume in obese adolescents with non alcoholic fatty liver disease. J Pediatr Endocrinol Metab.2010 Aug ;( 8):807-13.
5. Bhatia LS, Curzen NP, Byrne CD: Non alcoholic fatty liver disease and vascular risk. Curr Opin Cardiol.2012 Jun; 27(4):420-8.
6. Bhatia LS, Curzen NP, Calder PC, Byrne CD: Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor? Eur Heart J.2012 May; 33(10):1190-200.
7. Caserta CA, Pendino GM, Amante A, Vacalebre C, Fiorillo MT, Surace P, Messineo A, Surace M, Alicante S, Cotichini R, Zuin M, Rosmini F, Mele A, Marcucci F: cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy. Am J Epidemiol.2010 jun 1;171(11):1195-202.
8. Catena C, Bernardi S, Sabato N, Grillo A, Ermani M, Sechi LA, Fabris B, Carretta R, Fallo F: Ambulatory arterial stiffness indices and non-alcoholic fatty liver disease inessential hypertension. Nutr Metab Cardiovasc Dis.2012 Jul 13.
9. Chiang CH, Huang CC, Chan Wl, Chen JW, Leu HB: The severity of non-alcoholic fatty liver disease correlates with high sensitivity C-reactive protein value and is independently associated with increased cardiovascular risk in healthy population. Clin Biochem.2010 Dec; 43(18):1399-404.
10. Giovanni Targher, Lorenzo Bertolini, Felice Poli, Stefano Rodella, Luca Scala, Roberto Tessari, Luciano Zenari and Giancarlo Falezza: Nonalcoholic Fatty Liver Disease and Risk of Future Cardiovascular Events Among Type @ Diabetic patients. Diabetes.2006; 54.12.3541.
11. Huang Y, Bi Y, Xu M, Ma Z, Xu Y, Wang T, Li M, Liu Y, Lu J, Chen Y, Huang F, Xu B, Zhang J, Wang W, Li X, Ning G: non alcoholic fatty liver disease is associated with atherosclerosis in middle-age and elderly Chinese. Arterioscler Thromb Vasc Biol.2012 Sep; 32(9):2321-6. Epub 2012 Jul19.
12. Liu CJ: Prevalence and risk factors for non-alcoholic fatty liver disease in Asian people who are not obese. Journal of Gastroenterology and Hepatology, 2012; 27(10): 1555-1560.
13. Mantovani A, Zoppini G, Targher G, Golia G, Bonora E: Non-alcoholic fatty liver disease is independently associated with left ventricular hypertrophy in hypertensive Type 2 diabetic individuals. J Endocrinol Invest. 2012 Feb; 35(2):215-8.
14. Marchesini G, Brizi M, Bianchi S, Forlani G, Melchionda N: Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes.2001 Aug; 50(8):1844-50.
15. Min HK, Kapoor A, Fuchs M, Mirshahi F, Zhou h, Maher J, Kellum J, Warnick R, Contos MJ, Sanyal AJ: Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease. Cell Metab.2012 May 2(5):665-74.
16. Misra VL, Khasab M and Chalasani: Non-alcoholic Fatty Liver Disease and Cardiovascular Risk. Curr Gastroenterol Rep.2009 feb;11(1):50-5.
17. Miyake T, Kumagi T, Hirooka M, Koizumi M, Furukawa S, Ueda T, Tokumoto Y, Ikeda Y, Abe M, Kitai K, Hiasa Y, Matsuura B, Onji M: Metabolic markers and ALT cutoff level for diagnosing nonalcoholic fatty liver disease: a community-based cross-sectional stuy. J Gastroenterol. 2012 Jun; 47(6):696-703. Epub 2012 Feb 14.
18. Ndumele CE, Nasir K, Conceicao RD, Carvalho JA, Blumenthal RS, Santos RD: Hepatic steatosis, obesity and the metabolic syndrome are independently and sdditively associated with increased systemic inflammation. Arterioscler Thromb Vas Biol.2011 Aug;31(8):1927-32.
19. Paloma AV, Daniel CR, Carlos AAS: Metabolic syndrome and non alcoholic fatty liver disease. Annals of Hepatology; 8(1)2009: S18-S24 Annals of Hepatology 2009;8(1): S18-S24.