European Journal of Cardiovascular Medicine

Coronary artery disease (CAD) is one of the leading causes of mortality worldwide. Coronary artery disease also known as Ischemic heart disease is a condition in which there is an inadequate supply of blood and oxygen to a portion of the myocardium , it typically occurs when there is an imbalance between myocardial oxygen supply and demand.⁽⁵⁾ Decreased blood flow to the heart leads to myocardial ischemia (angina pectoris) and, if severe and prolonged, results in myocardial infarction (the heart attack)⁽⁷⁾.In more than 90% of cases, myocardial ischemia results from reduced blood flow due to obstructive atherosclerotic lesions in the epicardial coronary arteries.⁽⁶⁾ Usually, the disease starts with angina, and infarction occurs when the obstruction occupies at least 75% of the lumen of the coronary artery. The known risk factors for CAD are age (> 40 years), gender (males are more susceptible), family history, smoking, hypertension, hypercholesterolemia, diabetes, hemostatic factors (platelet activation, fibrinogen), physical inactivity, obesity, alcohol intake, hyperhomocysteinemia and stress⁽⁷⁾

In 1901 Karl Landsteiner discovered ABO blood group system. ABO system was the first blood group system to be known. ABO blood groups have been associated with various disease phenotypes, particularly cardiovascular diseases. Genome-Wide Association Studies have identified ABO as a locus for thrombosis and myocardial infarction. A number of studies have elucidated that ABO blood groups, particularly non-O blood groups, are associated with major cardiovascular risk factors and/or increased rate of cardiovascular events⁽¹⁾

Not limited to red cell membranes, ABO antigens are found on all tissues and are also expressed on von Willebrand factor (vWF) and FVIII. On vWF, ABO blood group antigens are attached near the site where ADAMTS13 cleaves vWF. The efficiency of proteolysis by ADAMTS13 is influenced by these neighboring ABO antigens, occurring more readily with O- than with non-O blood groups. The rate of VWF proteolysis by ADAMTS13, is higher in blood group O as compared to non-O individuals. This finding has been proposed as the major mechanism for the observation that vWF levels are higher in non-O vs. O- blood group patients. Since vWF is the plasma carrier for FVIII, non-O individuals also have higher FVIII levels. Von Willebrand factor is a major mediator of platelet adhesion to areas of arterial injury.⁽⁴⁾ VWF recruits platelets to the site of clot formation during primary hemostasis. Factor VIII is released from VWF by the action of thrombin and participates in the coagulation cascade. Thus, both VWF and FVIII are key proteins in the formation of occlusive thrombi in injured vessels. Therefore increase in plasma levels of VWF and Factor VIII are associated with greater risk of thrombosis. In 1976, Garrison et al. published an epidemiological analysis in the Framingham Heart Study showing consistent elevations of serum cholesterol levels in non-O blood groups when compared to the O blood group⁽¹⁾ Several prospective studies have shown that higher vWF levels predict future coronary heart disease events ⁽⁴⁾.

The aim of this study was to determine the association between ABO blood groups and the risk for coronary artery disease

This hospital based case control study was conducted at B.J Medical College & Civil hospital, Ahmedabad during the year 2016-2017. Hundred and ten (110) cases of coronary artery disease confirmed by coronary angiography and 110 healthy subjects without cardiovascular disease were enrolled in this study. Cases of coronary artery disease were recruited from patients attending the medicine outpatient department and those admitted in the medical wards. Apparently healthy staffs of hospital and medical college who volunteered to participate in the study as well as individuals attending OPD for non-cardiac complaints were enrolled as the controls. Data regarding blood group was collected from hospital medical records of the study participants. Inclusion criteria Patients diagnosed with coronary artery disease by coronary angiography. Exclusion Criteria Patients with congenital heart disease, rheumatic heart disease and other cardiovascular diseases were excluded from the study. DATA ANALYSIS Data were entered in excel sheet and the analysis was done using SPSS software. The association between ABO blood group and coronary artery disease was assessed using Chi square test. Odds ratio (OR) with 95% confidence interval (CI) was calculated to estimate the strength of association between ABO blood groups and CAD. Odds ratio was computed for individual blood groups using blood group O as the reference. A p value<0.05 was considered statistically significant.

Out of 110 CAD patients 83 (75%) were males and 27(25%) were females while out of 110 healthy subjects who were enrolled as controls 50(45%) were males and 60 (55%) were females. On studying the age distribution among CAD cases it was noted that most of the CAD cases were in the age group 51-60 years followed by 41-50 years.

TABLE 1: GENDER DISTRIBUTION AMONG CAD CASES AND CONTROL

FIGURE 1: GENDER DISTRIBUTION AMONG CAD CASES AND CONTROLS

TABLE 2: AGE DISTRIBUTION AMONG CAD CASES

FIGURE 2: AGE DISTRIBUTION AMONG CAD CASES

Among the control group 21(19%) had A blood group, 45 (41%) had B blood group, 6(5.5%) had AB blood group and 38(35%) had O blood group while among the CAD cases, 32 (29%) had A blood group, 40(36%) had B blood group,15(14%) had AB blood group and 23 (21%) had O blood group.

TABLE 3: DISTRIBUTION OF ABO BLOOD TYPES IN CAD CASES AND CONTROL GROUPS

FIGURE 3: ABO BLOOD GROUP DISTRIBUTION AMONG CAD CASES AND CONTROL (%)

FIGURE 4: DISTRIBUTION OF ABO BLOOD GROUPS IN CAD CASES

With blood group O as the reference category, the odds of CAD were found to be higher among individuals with non-O blood groups. The odds ratio for coronary artery disease was 2.518 in individuals with blood group A, 1.469 in individuals with B blood group and 4.13 in individuals with AB blood group. The highest odds was observed among individuals with AB blood group.

TABLE 4: ODDS RATIO OF CORONARY ARTERY DISEASE IN DIFFERENT BLOOD GROUPS

 * O blood group is taken as reference

 *p<0.05-SIGNIFICANT *p>0.05-NOT SIGNIFICANT

Among the CAD patients 75% were males and 25% were females. According to our study CAD risk is 3 times higher in males than females. This shows that males are more prone for coronary artery disease than females. Pre-menopausal women have higher estrogen levels, which are thought to provide a protective effect by maintaining the flexibility and function of the endothelial cells and enhancing vasodilation. After menopause, when estrogen levels drop, women become more vulnerable to CAD.⁽⁸⁾

On studying the age distribution among CAD cases it was noted that most of the CAD cases were in the age group of 51-60 years followed by 41-50 years.

In the control group 19% had A blood group, 41% had B blood group, 5.5% had AB blood group and 35% had O blood group. B blood group was the most common blood group in the control group followed by O, A and AB. The study of Patel Piyush et al. showed similar pattern of distribution of blood groups in Eastern Ahmedabad, the commonest being B blood group (36%) followed by O(33%), A(23%), AB(9%).⁽⁹⁾

Among the CAD cases, 29% had A blood group, 36% had B blood group,14% had AB blood group and 21% had O blood group. B blood group was the most prevalent in CAD cases followed by A, O and AB. But it was noted that blood groups A and AB were more common in cases than in control group while blood groups B and O were found to be more common in control group than in cases.

In this study, blood group O was taken as the reference category and odds ratio was estimated to assess the association between ABO blood groups and coronary artery disease. Individuals with blood group A had nearly 2.5 times higher odds of having coronary artery disease (CAD) compared to those with blood group O, indicating a moderate association between blood group A and CAD. There was statistically significant association between blood group A and CAD. Blood group B also showed a modestly increased risk, with approximately 1.5 times higher odds of CAD compared to blood group O, but this association was weaker and statistically non significant. Blood group AB demonstrated the strongest association with CAD, with individuals having this blood group showing more than fourfold higher odds of CAD compared to those with blood group O. The association of AB blood group with CAD was found to be statistically significant. In contrast, blood group O appeared to have the lowest risk of CAD and may be relatively protective against the development of coronary artery disease.

Therefore, our study shows that CAD risk is highest in individuals with AB blood group followed by A blood group. O blood group was found to be protective. According to our study, individuals with O blood group have lesser risk for CAD compared to non-O blood groups. This can be because individuals with O blood group have lower levels of VWF and factor VIII than non-O blood group. The high risk for CAD in non O blood groups can be attributed to high plasma levels of factor VIII and vWF. Several studies have reported that plasma levels of factor FVIII-vWF complex in non-O individuals were approximately 25% higher than in group O individuals. Elevated FVIII-vWF levels are a risk factor for coronary artery disease.

The vWF has an important role in hemostasis and thrombosis by mediating platelet adhesion to the vascular wall. Along with fibrinogen, vWF also participates in platelet aggregation. ABO blood group has been associated with plasma lipid levels; in particular, the A blood group has been noted to have higher levels of serum total cholesterol and low-density lipoprotein cholesterol.⁽¹¹⁾

The systematic review and meta analysis by Zhuo Chen et al. showed that the risk of CAD in blood group O was significantly lower than that in non-O groups. Their study also suggested that blood group A and non-O are associated with an increased risk of CAD⁽²⁾ The study of Xiaoying et al. also suggested that non-O blood group is associated with the increased risk of CAD⁽¹⁰⁾. As per the study of Manimekalai et al. and Umesh Pai et al. the incidence of coronary artery disease was higher in blood group A ^(12,13). But the study of Santanu Biswas et al. showed that O blood group increases the risk of CAD while AB blood group decreases the risk of CAD⁽³⁾.

Our study suggests that the risk for coronary artery disease is high in individuals with non-O blood groups, particularly AB and A blood groups compared to O blood group.

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