Asian Cardiovasc Thorac Ann 2006;14:119-122
© 2006 Asia Publishing EXchange Ltd
Rhesus Positivity and Low High-Density Lipoprotein Cholesterol: A New Link?
Mehmet Kanbay, MD,
Aylin Yildirir, MD1,
Taner Ulus, MD1,
Muhammet Bilgi, MD1,
Alparslan Kucuk, MD1,
Haldun Muderrisoglu, MD1
Department of Internal Medicine
1 Department of Cardiology, Baskent University Faculty of Medicine, Ankara, Turkey
For reprint information contact: Mehmet Kanbay, MD Tel: 90 312 222 0398 Fax: 90 312 213 0034 Email: drkanbay{at}yahoo.com, Department of Internal Medicine, Department of Cardiology, Baskent University Faculty of Medicine, 35. Sokak, 81/5, Bahcelievler, Ankara 06490, Turkey.
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ABSTRACT
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The aim of the study was to investigate the relationship of ABO and Rh blood groups with lipid profile in patients with established multivessel coronary artery disease in a population with low levels of high-density lipoprotein cholesterol. The records of 978 patients with multivessel coronary artery disease, in whom coronary bypass surgery was performed, were investigated. Coronary risk factors including diabetes, hypertension, smoking, and obesity were noted for each patient. Serum lipid profiles: total cholesterol, low-density and high-density lipoprotein cholesterol, and triglyceride levels, were also recorded. The mean age of the patients was 59.3 ± 9.7 years (range, 25–84 years) and 80% were male. The risk factors and lipid profiles of ABO blood types were similar. Rh-negative patients had higher levels of high-density lipoprotein cholesterol (46.9 ± 9.9 vs. 41.6 ± 10.4 mg·dL–1, p = 0.001) and a lower total/high-density lipoprotein cholesterol ratio (4.8 ± 1.3 vs. 5.2 ± 1.6, p = 0.029) compared to Rh-positive patients. The other lipid levels and risk factors had no association with Rh typing. These results indicate a significant association between rhesus positivity and low levels of high-density lipoprotein cholesterol in patients with multivessel coronary artery disease.
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INTRODUCTION
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Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality worldwide.1,2 Hyperlipidemia ranks second only to age as a predictor of CAD.1,2 This condition results from accelerated synthesis or decreased degradation of the lipoproteins that transport cholesterol and triglycerides in plasma. This abnormal metabolism may be genetic, diet-related, or due to secondary disease. Research has demonstrated a strong, independent, continuous, and graded relationship between the risk of CAD events and levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C).2–4 During the last few decades, many studies have demonstrated a link between ABO blood groups, in particular non-O blood groups, and the risk of developing severe manifestations of atherosclerosis.5–10 However, no data are available regarding the association between rhesus (Rh) blood typing and atherosclerosis. It is well known that the Turkish population has low HDL-C relative to other populations, but the reason for this is still unclear.11–13 Turkish patients were investigated for links between ABO-Rh blood type and HDL-C levels.
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PATIENTS AND METHODS
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The records of 978 patients with multivessel CAD who had undergone coronary artery bypass surgery were retrospectively analyzed. The subjects comprised 786 (80%) males and 192 (20%) females, aged 25 – 84 years (mean age, 59.3 ± 9.7 years). All had been operated on in the Cardiovascular Surgery Department of Baskent University Faculty of Medicine from 1999 through 2002. In each case, risk factors for CAD, including diabetes mellitus, hypertension, smoking, and obesity (body mass index > 25 kg·m–2) were noted. Fasting plasma levels of homocysteine, 
-lipoprotein, uric acid, and lipid profile parameters (TC, LDL-C, HDL-C, and triglyceride) were also recorded. The patients were grouped according to ABO-Rh blood type.
Statistical analysis was performed with SPSS version 9.0 for Windows (SPSS, Inc., Chicago, IL, USA). Groups were compared using the chi-squared test, independent samples t test, and analysis of variance. Variables were first tested with univariate analysis, and subsequently by stepwise multivariate regression analysis. The data are expressed as percentages or mean ± standard deviation. All p values < 0.05 were considered statistically significant.
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RESULTS
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The risk factors for CAD in the 978 patients were: diabetes mellitus 30%, hypertension 52%, obesity 76%, and smoking 50%. The distribution of blood groups is shown in Figure 1
. Regarding Rh antigen status, 87.6% of the patients were Rh+ and 12.4% were Rh–. The prevalence of Rh negativity in Turkey is 11.4%, no different from our study population. The prevalence of Rh positivity according to sex and ABO blood group is shown in Table 1. As in previous studies, blood group A predominated, but the proportion of patients with this blood type was not significantly higher than the proportions of other blood types (p > 0.05 for all). The frequencies of risk factors for CAD and elevated lipid profile parameters were similar among all blood groups. None of the ABO blood types was significantly associated with any of the risk factors investigated.
Concerning lipid profiles, 47.8% of the 978 patients had low HDL-C (< 40 mg·dL–1) levels. Although there were no significant differences in lipid levels among blood types (Table 2), the Rh+ group had a significantly lower mean HDL-C level than the Rh– group (41.6 ± 10.4 vs. 46.9 ± 9.9 mg·dL–1, p = 0.001) and a significantly higher mean TC/HDL-C ratio than the Rh- patients (5.2 ± 1.6 vs. 4.8 ± 1.3, p = 0.029). None of the other lipid parameters and none of the risk factors for CAD were significantly associated with Rh status. The prevalence of HDL-C < 40 mg·dL–1 in the Rh– patients was 29.4%, whereas the rate in the Rh+ group was 51.4% (p < 0.0001). The 978 patients were also divided according to age; there was no relationship between lipid levels and blood type within the age groups. When we compared younger (< 55 years) vs. older (> 55 years) age groups, the relationship between low HDL-C and Rh positivity was more striking in the younger patients (41.1 ± 9.0 vs. 47.5 ± 9.0 mg·dL–1, p = 0.002), but also important for the older group (41.8 ± 11.1 vs. 46.5 ± 10.4 mg·dL–1, p = 0.004).
Univariant analysis was performed to identify predictors of HDL-C levels. This analysis showed that diabetes (
2 = 5.62, p < 0.001), Rh positivity (2 = 5.21, p < 0.001), older age (2 = 4.23, p < 0.01), male sex (2 = 4.02, p < 0.005), obesity (2 = 3.32, p < 0.04), and smoking (2 = 3.07, p < 0.02) were associated with lower levels of HDL-C. Multivariate analysis by logistic regression was performed to adjust for the covariates: diabetes, older age, male sex, obesity, Rh positivity, and smoking. This analysis identified diabetes ( p < 0.001, RR = 3.814), Rh positivity (p < 0.001, RR = 3.193), and male sex ( p < 0.01, RR = 1.932) as independent risk factors for a low level of HDL-C.
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DISCUSSION
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Epidemiologic studies have identified important risk factors for CAD, including age, hypertension, diabetes, sedentary lifestyle, obesity, tobacco use, elevated LDL-C, elevated TC, and depressed HDL-C.1–5 Next to age, hyperlipidemia is the most important predictor of CAD.2–5 This relationship holds true for men, women, and all age groups. Fatty streaks, the earliest lesions of atherosclerosis, are present in the aorta from early childhood. Recently, it has been established that atherosclerosis begins during fetal development.3 Some individuals are more susceptible to atherosclerosis; however, many of the risk factors for atherosclerosis, blood lipid levels in particular, are modifiable and amenable to treatment.3–5 This has led to increased interest in the benefits of lipid-lowering therapy, and in genetic predisposition to hyperlipidemia.10,11
The association between ABO blood groups and CAD is still unclear despite many studies addressing this topic. Blood type A predominated in our patients, as expected, but the frequency of type A was not significantly higher than the frequencies of the other blood types. Most previous reports have indicated that AB blood groups predominate in CAD patients, and that type O blood is a protective anti-atherogenic factor.5–10 Two separate studies indicated that blood type A is not a risk factor for atherosclerosis, type B can be associated with coronary atherosclerosis, and type O may serve as a protective anti-atherogenic factor in women.5,6 Cronenwett and colleagues9 identified blood type A as an independent risk factor for peripheral occlusive disease. Horby and colleagues6 reported that types A and B are genetically based risk factors for the pathogenesis of atherosclerosis. In contrast to these findings, when we categorized our subjects according to ABO blood type, we found no statistical differences among the groups with respect to any of the biochemical parameters investigated. However, when the patients were analyzed according to Rh status, the Rh+ group had significantly lower HDL-C levels and higher TC/HDL-C ratio than the Rh– group; this held true for younger and older age groups, and was independent of sex or body mass index. The correlation between low HDL-C and Rh+ status was strongest in the younger age group. Thus, Rh+ individuals may be predisposed to CAD through one of the major risk factors. Our results strongly suggest that there is a genetic link between Rh status and dyslipidemia, specifically with low HDL-C. To the best of our knowledge, this is the first study demonstrating an association between Rh-positive status and dyslipidemia.
Presented in part in the 74th Congress of the European Atherosclerosis Society, April 17–20, 2004, Seville, Spain.
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REFERENCES
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- Fuster V. Epidemic of cardiovascular disease and stroke: the three main challenges. Circulation 1999;99:1132–7.[Free Full Text]
- Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 1997;349:1269–76.[Medline]
- Napoli C, Glass CK, Witztum JL, Deutsch R, D’Armiento FP, Palinski W. Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: Fate of Early Lesions in Children (FELIC) study. Lancet 1999;354:1234–41.[Medline]
- Anderson KM, Wilson PW, Odell PM, Kannel WB. An updated coronary risk profile. A statement for health professionals. Circulation 1991;83:356–62.[Free Full Text]
- Stakisaitis D, Maksvytis A, Benetis R, Viikmaa M. Coronary atherosclerosis and blood groups of ABO system in women. Medicina (Kaunas) 2002;38(Suppl 2):230–5.
- Horby J, Gyrtrup HJ, Grande P, Vestergaard A. Relation of serum lipoproteins and lipids to the ABO blood groups in patients with intermittent claudication. J Cardiovasc Surg (Torino) 1989;30:533–7.[Medline]
- Meade TW, Cooper JA, Stirling Y, Howarth DJ, Ruddock V, Miller GJ. Factor VIII, ABO blood group and the incidence of ischaemic heart disease. Br J Haematol 1994;88:601–7.[Medline]
- Wong FL, Kodama K, Sasaki H, Yamada M, Hamilton HB. Longitudinal study of the association between ABO phenotype and total serum cholesterol in a Japanese cohort. Genet Epidemiol 1992;9:405–18.[Medline]
- Cronenwett JL, Davis JT Jr, Garrett HE. ABO blood group and serum lipids in female atherosclerosis. J Cardiovasc Surg (Torino) 1983;24:658–61.[Medline]
- Grover SA, Palmer CS, Coupal L. Serum lipid screening to identify high-risk individuals for coronary death. The results of the Lipid Research Clinics prevalence cohort. Arch Intern Med 1994;154:679–84.[Abstract/Free Full Text]
- Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987;317:1237–45.[Abstract]
- Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996;335:1001–9.[Abstract/Free Full Text]
- Onat A, Senocak MS, Surdum-Avci G, Ornek E. Prevalence of coronary heart disease in Turkish adults. Int J Cardiol 1993;39:23–31.[Medline]
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ABSTRACT
INTRODUCTION
