ABO blood groups and atherosclerosis

Atherosclerosis,

18 (1973) 347-351

347

0 Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands

letter

ABO

to the Editors

BLOOD

GROUPS

AND

ATHEROSCLEROSIS

Sirs, normal

The existence, in normal mean level of esterified

subjects of blood serum-cholesterol1

group A, of a slightly higher-thanand perhaps of serum-triglycerides

and beta-lipoproteins clearly suggests the possibility of an association between blood group A and atherosclerosis. The same possibility is suggested by the known association between blood group A and arterial thrombosi+-6, in that arterial thrombosis and atherosclerosis are believed to be so intimately related’s, however distincts, that the most fundamental point in question is their relative priorityrs~lr. Accordingly it may be useful to draw together the rest of the evidence on the matter, beginning with evidence in jizvour of an association between blood group A and atherosclerosis, proceeding to evidence which is at present problematic, and continuing with evidence against. between blood group A and atherosclerosis is In favour of an association Jaegermann’@ series of 829 forensic autopsies on unselected cases of sudden death. It is true that, over this series us a whole the ratio of blood group A to blood group 0 is normal, as is (atypically) that of the 10 “/, of deaths in the series which were ascribed to coronary thrombosis. Within the series, however, the A/O ratio is significantly higher (P < 0.05) for cases with extensive coronary atherosclerosis at any age, or with slight coronary atherosclerosis before the age of 40, than for those aged over 40 with either slight coronary atherosclerosis or none. The details are shown in Table 1, in which the categories of atherosclerosis distinguished are, for convenience, labelled respectively “extensive or early” and “slight or absent”. The less common blood groups, AB and B, can, in this context, be disregarded. series of male The problematic piece of evidence resides in Kingsbury’&14 cases of peripheral atherosclerosis - cases which had presented with claudication and were assessed by arteriogram. In this series the A/O ratio is, in complete contrast, significantly higher (P < 0.005) for cases with slight than for those with moderate or extensive peripheral atherosclerosis; and the difference is at least as great in the absence as in the presence of occlusion. (The details are shown in Table 2, in which the categories of atherosclerosis distinguished are labelled “slight” and “considerable”, the findings being similar for moderate and extensive atherosclerosis.) The description

Key words: ABO blood groups - Atherosclerosis - Thrombosis

348 TABLE

T. M. ALLAN 1 A AND OINASERIESOFUNSELECTEDMALE ANDFEMALEFORENSICAUTOPSY SUDDENDEATH,BY EXTENTOF CORONARY ATHEROSCLEROSIS (DATAOF JAEGERMANN’~)

INCIDENCEOFBLOODGROUPS CASES OF

Number Coronary

atherosclerosis

of cadavers

Sex A

0

A/O

x::

P

Slight or absent Extensive or early

M

66 159

16 123

0.87 1.29

3.33

> 0.05

Slight or absent Extensive or early

F

41 61

38 37

1.08 1.65

1.52

> 0.20

Slight or absent Extensive or early

M+F

107 220

114 160

0.94 1.37

4.69

< 0.05

Total observed Total expected

M+F

327 321.3

274 275.3

1.19 1.17

0.02

> 0.80

Slight or absent

M F

66 41

76 38

0.87 1.08

0.40

> 0.50

Extensive or early

M F

159 61

123 37

1.29 1.65

0.80

> 0.30

TABLE

2

INCIDENCE OF BLOOD GROUPS

A AND 0 INASERIESOFMALECASESOFPERIPHERALATHEROSCLEROSIS,BY

EXTENT OF PERIPHERAL ATHEROSCLEROSIS AND

BY NUMBER

No. of patients Peripheral

atherosclerosis

1+

Slight Considerable

none

Slight Considerable Total observed Total expected

Considerable

1+ none 1+ none

OF KINGSBURY'3~1")

(male)

Occlusions

Slight Considerable

Slight

OF OCCLUSIONS(DATA

x”,

P

1.89 1.29

3.15

> 0.05

14 45

1.64 0.58

5.41

< 0.02

138 172

75 158

1.84 1.09

7.97

< 0.005

310 273.1

233 285.7

1.33 0.96

7.14

< 0.01

115 23 146 26

61 14 113 45

1.89 1.64 1.29 0.58

0.03

> 0.50

7.94

< 0.005

A

0

AI0

115 146

61 113

23 26

of this result as problematic is due not only to the difficulties inherent in arteriographic assessment of degree of atherosclerosis but also to the fact that only an A/O ratio not differing significantly with any degree of atherosclerosis would unequivocally constitute a negative finding. A possible example of the sort of situation which might give rise to such a result as this of Kingsbury’s is one whereby a peripheral, as opposed to a coronary, atherogenic effect of the A gene might be swamped, as age advances, by

ABO

BLOOD

GROUPS

other atherogenic

AND ATHEROSCLEROSIS

effects, genetic,

data on age were not provided

349

environmental in relation

or both. In this instance,

to degree of atherosclerosis.

however,

The overall

age-range was 35-75. Clearly against the possibility of an association between blood group A and atherosclerosis are three pieces of circumstantial evidence. Firstly, in atherosclerotic aneurysm a normal A/O ratio is found in all three series reported to date, the cases being respectively femoro-popliteal or aorto-iliac14, popliteal or aortW and abdominal aorticl6. (In two of these series 14y16the patients’ mean age was not given, but in the third15 it was 59 years for the aortic cases.) Secondly, in hypertension, which aggravates minor atherosclerosis, a normal A/O ratio is found in the aggregate of the six series reported to datel7. Thirdly, in angina pectoris, which is associated with coronary atherosclerosis, a normal A/O ratio is found, at least in general18, in fourls-21 of the five series reported to date1s-22. There remains the complication that a high A/O ratio is certainly found not only in arterial but also in venous thrombosiszs, and is possibly found in superficial puerperal thrombophlebitis24. As these last two conditions are characterised by absence of atherosclerosis, at any rate locally, this absence may be all the more significant in the context, in so far as the high A/O ratio found in venous thrombosis23 is and highest, on the evidence to date6,25-27, in cases associated with oral contraception, also in so far as there is evidence that oestrogen may be u?zt&atherogenic28,29. In sum, therefore, present evidence suffices merely to pose, not to answer, the question whether any association exists between blood group A and atherosclerosis, of atherosclerosis to thrombosis, whatever either per se or through the relationship that may prove to be. Perhaps clearer evidence one way or the other would be provided by comprehensive prospective post-mortem surveys of the extent and distribution of co-existing peripheral and coronary atherosclerosis (in both male and female cases of different age groups, ABO blood groups, ABO sub-groups4~7~22~2s~sO~sl and ABH secretor-statuss2); the data being assembled both from series of unselected cases and series of cases of previously-recognised arterial disease, whether peripheral or coronary, with due regard to concomitant blood-group-associated diseases, such as duodenal ulcer and stomach cancer. Some of the unselected cases would have to be blood-grouped from post-mortem samples, but this would seldom present any difficulty. ACKNOWLEDGEMENTS

I am grateful to Drs. H. B. M. Lewis, E. B. Smith and A. A. Dawson comment.

for helpful

SUMMARY

Despite the known existence of an association between blood thrombosis, available evidence is conflicting with regard to the possibility

group A and of an associ-

T. M. ALLAN

350

ation between blood group A and atherosclerosis. Evidence in favour of such an association is provided by Jaegermann’s series of coronary atherosclerosis cases, and problematic evidence is provided by Kingsbury’s series of peripheral atherosclerosis cases, while circumstantial evidence against is provided by several sources. It is suggested that clearer evidence one way or other might be obtained from post-mortem surveys of co-existing

peripheral

and coronary

atherosclerosis.

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ABO BLOOD GROUPS AND ATHEROSCLEROSIS

351

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Blood Transfusion Centre, Royal Znjirmary, Aberdeen AB9 2ZW (Great Britain) (Received May lOth, 1973)

T. M. ALLAN