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Journal of the Anatomical Society of India

Histomorphometric Analysis Of Coronary Arteries: Sexual Dimorphism

Author(s): Dhall, U; Chaudhary, S. and *Sirohiwal, B.L.

Vol. 52, No. 2 (2003-07 - 2003-12)

Department of Anatomy & *Forensic Medicine, Pt. B. D. Sharma PGIMS, Rohtak-(INDIA)

Abstract

Sex differences in the histomorphometry of coronary arteries were studied in 25 male and 25 female autopsied heart specimens ranging in age between 20 and 40 years. The lumen diameter and thickness of tunica media and tunica intima were measured in paraffin sections of five specimens of coronary arteries from each heart using point-counting and linear-intercept techniques. Although the mean lumen diameter of the vessels studied was more in males as compared to females but relative to heart weight coronaries were found to be wider in females suggesting better coronary flow in females. Tunica intima was found to be thicker in males in absolute terms as well as relative to the diameter. This may form the basis for higher incidence of atherosclerosis, a disease of tunica intima, in males. These quantitative differences in the structure of coronary arteries can explain at least to some extent, the sex differential in the coronary artery disease.

Key words: Coronary arteries, atherosclerosis & Coronary artery disease, angina pectoris, myocardial infarction.

Introduction:

Coronary artery disease is a major cause of human mortality and morbidity. It is also established that the incidence of coronary artery disease is much higher in men than in women until the fourth- fifth decades of life when it increases more steeply in women than in men (Kalin and Zumoff, 1990). The reasons for this difference are, however, not fully understood. It has been speculated that the protective factor may be the female hormone estrogen which favourably affects lipid metabolism slowing down the process of atherosclerosis in coronary arteries (Walsh et al., 1991). It is well known that blood flow through arteries is influenced by various mechanical and hydraulic factors (Braunwald, 1992), but sex differences in morphometric features of coronaries like diameter and wall thickness do not seem to have attracted much attention as evidenced by paucity of publications. The present study is, therefore aimed to analyse histomorphometric features of coronary arteries which may add to the understanding of sexual differences in coronary artery disease.

Material and Methods:

This study was conducted on 50 human hearts (25 male, 25 female) obtained from medicolegal autopsies done in the Department of Forensic Medicine Sciences, Pt. B.D. Sharma PGIMS, Rohtak. The age group studied varied between 20 and 40 years to avoid major cardiac pathology. The cause of death was due to accident, either suicide or murder and, therefore, occurred suddenly. Weight was recorded and hearts weighing more than 370 gms in males and 280 gms in females were excluded from the study to avoid the possibility of hypertensive cases. Hearts showing obvious pathological changes of atherosclerosis were also excluded. After fixation (by immersion in 10% formaldehyde solution) coronary arteries were dissected and tissue pieces were taken for processing from the following sites.

  1. Right coronary near origin (RCA-1)
  2. Right coronary 2.5cm from origin (RCA-II)
  3. Left coronary stem (LCA)
  4. Anterior interventricular artery 5mm from its origin (AIV)
  5. Circumflex artery 5mm from its origin (CX)

Paraffin sections seven micron thick were stained with Verhoeff's stain which delineated the internal elastic lamina clearly. Three step-sections from each piece at interval of 70m were subjected to morphometric analysis using a microprojector (magnification x 40). The profile of each section was drawn outlining the endothelial lining, internal elastic lamina and outer margin of tunica media carefully on a white sheet. Using appropriate grids for point- counting and linear-intercept techniques, the area of tunica media and tunica intima, and lumen circumference were measured. Then from these parameters thickness of tunica media (Tm), thickness of tunica intima (Ti) and lumen diameter (D) were calculated as described by Aherne and Dunnill (1982). Results were analysed statistically using student t- test.

Results:

Mean heart weight in males and females was 262.6 ± 8.4 gms and 220.3 ± 6.7 gms respectively.

Figures 1-5 and Table I compare the morphometric features of the coronary arteries in two sexes. The important ohservations are as follows:

  1. The mean lumen diameter of all the vessels (except LCA where it is equal) is more in males as compared to females (Fig.1). The difference was found to be statistically significant for anterior interventricular artery (P < 0.05).
  2. The thickness of tunica intima is more in males as compared to females in RCA-II, AIV and CX-arteries (Fig.2)
  3. The thickness of tunica media is more in males as compared to females (Fig.3).
  4. When Tm : Ti was calculated it was observed that this ratio was lower in males for anterior interventricular, circumflex and distal part of right coronary arteries (Fig.4).
  5. When D : Ti was calculated it was observed that the ratio was lower in males (Fig.5).
  6. Relative to the heart weight the diameter was more in females than in males (Table 1)

Table-1: Diameter of Coronary Arteries in relation to heart weight

Arteries Diameter (mm): Heart Weight (gms.)
Male Female
Left Coronary 8.1 9.6
Right Coronary near origin 6.1 6.8
Right Coronary 2.5cm from origin 6.1 6.5
Anterior Interventricular 6.2 6.6
Circumflex 6.9 7.4

Discussion:

The present study has highlighted some of the histomorphometric differences in the male and female coronary arteries which may help to explain the sex differential in the incidence of coronary artery disease. Although these differences observed are not found to be statistically significant but a definite trend can be observed. The earlier publications concerning morphometric differences in coronaries have either compared lumen diameter or wall thickness. The authors could not find any publication that compared all the parameters simultaneously.

The lumen diameter was found to be more in males as compared to females consistent with the earlier reports (Macalpin et al., 1973; Robert and Robert, 1980; Dodge et al., 1992). Macalpin et al (1973) reported that differences in lumen calibre between men and women could be acceptably resolved when total coronary area was normalised to body surface area. Dodge et al (1992), however, observed such differences to persist after adjustment for body size. Robert and Robert (1980) stated that sex differences in lumen diameter disappeared when coronary size was adjusted for heart weight. However, in the present study when lumen size was compared to heart weight (Table 1), it was observed that all the coronaries studied were wider in relation to heart weight in women indicating better coronary flow in females. This could be one of the factors contributing to lower incidence of coronary artery disease in women.

The present study revealed that in general tunica intima was thicker in adult males not only in absolute terms but also relative to tunica media and to lumen size. Thicker intima in males has been reported in newborns (Dock,1945) fetuses and children of Askhenazy Jews (Vlodaver et al., 1969) and adults (Velican and Velican, 1981). On the other hand Moon (1957) reported absence of consistent sex differences in intimal thickness of main coronary arteries of male and female fetuses, infants and juveniles ranging in age from zero to 22 years. The finding of thicker tunica intima in males is important in relation to higher incidence of coronary artery disease in man which is usually due to atherosclerosis (Helander and Levander, 1959; Peel, 1955) a disease that primarily invloves tunica intima. Interestingly women are more prone to nonatherosclerotic coronary artery disease as compared to men. It is reported that angina pectoris was predominant initial presentation of coronary artery disease among women, occurring in 56% of women as compared to 43% men (Douglas, 1969) The present study revealed that Tm : Ti was lower in males. In other words women had thicker tunica media relative to tunica intima. This may explain higher incidence of spasm of coronary arteries in females since tunica media is predominantly made up of smooth muscle.

Understanding the pathogenesis of coronary heart disease is essential for both the presentation and the treatment of ischaemia. Pathophysiological mechanism operating in coronary vessels seem to be different in two sexes leading to differences in the clinical profile of the disease. The present study showing morphometric differences in the wall and diameter of coronary arteries in two sexes throws some light on these pathophysiological mechanisms. More research is, however,needed to further clarify these processes. One interesting aspect would be to study the density of autonomic nerves in coronaries in view of the different threshold for stress in two sexes.

References:

  1. Aherne, W.A. and Dunnill, M.S : Morphometry. London : Edward Arnold, pp. 155-157. (1982)
  2. Braunwald, E. Heart disease. A text book of cardiovascular medicine. 4th ed. W.B. Saunders Co., Philadelphia, pp. 1161-1199. (1992)
  3. Dock, W. (1945) : The predilection of atherosclerosis for the coronary arteries. Journal of American Medical Association 131 : 39-50.
  4. Dodge, J.T., Brown B.G., Bolson E.L. and Dodge H.T. (1992): Lumen diameter of normal Human coronary arteries : Influence of age, sex, anatomic variation and left ventricular hypertrophy or dilation. Circulation 86 : 232-246.
  5. Douglas, P.S. : Heart disease in women. F.A. Davis Company, Philadelphia, p. 144 (1969)
  6. Helander , S and Levander, M. (1959) : The primary mortality and the 5 years prognosis of cardiac infarction Acta Medical Scandinavia 163 : 289-296.
  7. Kalin. M.F. and Zumoff B., (1990) : Sex hormones and coronary disease : A review of the clinical studies. Steroids 55 : 330-352.
  8. Macalpin, R.N., Abbasi,A.S. Grollman, J.H and Eber, L. (1973): Human coronary artery size during life: A cinearteriographic study. Radiology 108 : 567-576.
  9. Moon, H.D. (1957) : Coronary arteries in fetuses, infants and juveniles. Circulation 16 : 263-269.
  10. Peel, A.A.F. (1955) : Age and sex factors in coronary artery disease. British Heart Journal 17 : 319-326.
  11. Roberts, C.S. and Robert W.C (1980) : Cross sectional area of the proximal portions of the three major epicardial coronary arteries in 98 necropsy patients with different coronary effects.Relationship to heart weight, age and sex. Circulation 62 : 953-959.
  12. Velican, D. and Velican C. (1981) : Comparative study of age related changes and atherosclerotic involvement of the coronary arteries of male and female subjects upto 40 years of age. Atherosclerosis 38 : 39-50.
  13. Vlodaver, Z. Khan H.A. and Neufeld H. (1969) : The coronary arteries in early life in three different ethnic groups. Circulation 39 : 541-550.
  14. Walsh, B.W., Schiff I., Rosner B., Green Berg, L. Ravinkar V., and Sacks F.M. (1991) : Effects of postmenopausal estrogen replacement on the concentration and metabolism of plasma lipo-proteins. New England Journal of Medicine 325 : 1196-1204.

Missing Image

Fig. 1- Sexual Dimorphism in lumen diameter (m) of different branches of coronary arteries.

LCA-Left coronary artery;
RCA-I-Proximal part of right coronary artery.
RCA-II-distal part of right coronary artery.
AIV-Anterior interventricular artery
Cx- Circumflex artery

 

Missing Image

Fig. 2- Sexual Dimorphism in thickness of tunica intima

(m) of different branches of coronary arteries.
LCA-Left coronary artery;
RCA-I-Proximal part of right coronary artery.
RCA-II-distal part of right coronary artery.
AIV-Anterior interventricular artery
Cx- Circumflex artery

 

Missing Image

Fig. 3- Sexual Dimorphism in thickness of tunica media

(m) of different branches of coronary arteries.
LCA-Left coronary artery;
RCA-I-Proximal part of right coronary artery.
RCA-II-distal part of right coronary artery.
AIV-Anterior interventricular artery
Cx- Circumflex artery

 

Missing Image

Fig.4 - Sexual Dimorphism in ratio of tunica media to tunica intima of different branches of coronary arteries.

LCA-Left coronary artery;
RCA-I-Proximal part of right coronary artery.
RCA-II-distal part of right coronary artery.
AIV-Anterior interventricular artery
Cx- Circumflex artery

 

Missing Image

Fig. 5- Sexual Dimorphism in ratio of lumen diameter to thickness of tunica intima of different branches of coronary arteries.

LCA-Left coronary artery;
RCA-I-Proximal part of right coronary artery.
RCA-II-distal part of right coronary artery.
AIV-Anterior interventricular artery
Cx- Circumflex artery

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