349
Atherosclerosis, 34 (1979) 349--351 9 Elsevier/North-Holland Scientific Publishers, Ltd.
Letter to the Editors C H O L E S T E R O L CONTENT O F THE HUMAN ATRIUM IS R E L A T E D TO PLASMA LIPOPROTEIN LEVELS
Sirs: Nestel and Poyser [1] examined the relations between the cholesterol content of the atrium and plasma lipoprotein lipid concentrations in 30 men and 8 women who required surgery for coronary heart disease. Atrial cholesterol content correlated with none of the lipoprotein lipid concentrations in these patients except for a positive association with very low density lipoprotein (VLDL) cholesterol (r = +0.32, P < 0.05). In fact it can be shown that even this relation disappeared after logarithmic transformation of VLDL cholesterol to allow for its skewed distribution. Nevertheless, there was a suggestion that patients with the highest concentrations of cholesterol in atrial tissue tended to a more severe form o f atheromatous dyslipoproteinaemia than the remainder. In view o f the importance of these data I have extended the analysis, which has provided further evidence for an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentration and the cholesterol content of extra-hepatic tissues [2]. If atrial cholesterol content increases with time, b u t the rate of accumulation is influenced by plasma lipoprotein concentrations, then there is interaction between time and lipoprotein concentration. This effect can be sought b y simultaneous (multiple) regression of atrial cholesterol on time (Xl), lipoprotein concentration (X2) and the interaction term (X,, X2). In the case o f HDL cholesterol, the interaction term should be statistically significant (P < 0.05) and of negative sign in order to support the hypothesis that this lipoprotein reduces the rate of cholesterol accumulation in extra-hepatic tissues. For LDL and V L D L the interaction terms should be significant b u t positive when high concentrations increase the rate o f cholesterol accumulation. The variable factor " t i m e " requires further consideration. This is the period during which cholesterol has been accumulating in the atrium at the adult rate. Its correct estimate is important because it partly determines the value and significance o f the interaction term and thus the conclusions o f the analysis. If the process has progressed steadily from birth then " t i m e " can b e equated with age. If on the other hand the adult pattern is established only after adolescence then the factor might be say, (age--20 years). The analysis confirmed that whichever definition was used atrial cholesterol content increased with time (P < 0.001) and that the interaction term of time with H D L cholesterol was always negative. However, the interaction term failed to achieve the conventional level o f statistical significance b y a small margin when time equalled age, but did reach significance (P ~ 0.02) when the process was assumed to have
350 1.6 1,5 1,4 9 1,3
1.2 _J
oL~ 1.1 -~ 1.0 i-
0.9 0.8
40
50
60
YEARS OF ACCUMULATION (AGE -5) Fig. I . R e l a t i o n b e t w e e n a t r i a l tissue cholesterol concentration a n d y e a r s o f a c c u m u l a t i o n ( d e f i n e d as age----5 y e a r s ) a t s t a n d a r d h i g h density llpopzotein (HDL) c h o l e s t e r o l c o n c e n t r a t i o n s o f 3 0 a n d 6 0 mg/ 1 0 0 m l . D a t a are t h o s e o f Nestel and P o y s e r [ 1 ] .
c o m m e n c e d in early childhood ("time ' ' = age--5 years). When (age--20 years) was used the interaction term was highly significant (P < 0.001). The figure illustrates the case when '~years of accumulation" was assumed to be (age-5 years). This shows that in the youngest patients atrial cholesterol appeared unrelated to H D L concentration b u t that thereafter the concentration of cholesterol in the atrium increased with time to a greater extent in those with a low HDL cholesterol than in those with a high concentration. By contrast, the analysis did n o t show that these patients with a high LDL or VLDL concentration had an increased rate of accumulation of atrial cholesterol relative to that of the remainder. These results must be interpreted with caution in such a selected group, b u t appear to support another report that in hypercholesterolaemic middle-aged patients, tissue cholesterol content is inversely related to plasma HDL cholesterol concentration [2]. The findings might mean that the supposed protective effect of HDL [3] becomes detectable in this t y p e of patient only when tissue cholesterol accumulation is well established. They do not exclude an association with other lipoproteins. For example, any association of LDL cholesterol with atrial cholesterol might be more obvious during younger adulthood and weaken as age advances, as is suggested b y prospective studies o f lipoproteins and coronary heart disease [4]. Atrial cholesterol is not s y n o n y m o u s with intimal atheroma, b u t the results support the view that a high HDL might retard the rate of accumulation of cholesterol in peripheral tissues, and thereby afford some protection against (but clearly not necessarily prevent) coronary heart disease.
351
References 1 Nestel, P.J. and Poyser, A., Cholesterol content of the h u m a n atrium is related to plasma lipoprotein levels, Athezosclezosis0 30 (1978) 177. 2 Miller, N.E., Nestel, P,J. and Cilfton-Bligh, p., Relationships between plasma lipoprotein cholesterol concentrations and the pool size and metabolism of cholesterol in man, Atherosclerosis, 23 (1976) 535. 3 Miller, G.J. and Miller, N.E., Plasma high-density Hpoprotein concentration and development of ischaemic heart disease, Lancet, I (1975) 16. 4 Gofman, J.W., Young, W. and "randy, R., Ischemic heart disease, atherosclerosis, and longevity, Circulation, 34 (1966) 679.
16--18 Jamaica Boulevard, P.O. Box 164, Federation Park, Port-of-Spain, Trinidad (W.L )
George J. Miller
Atherosclerosis, 34 (1979) 349--351 9 Elsevier/North-Holland Scientific Publishers, Ltd.
Letter to the Editors C H O L E S T E R O L CONTENT O F THE HUMAN ATRIUM IS R E L A T E D TO PLASMA LIPOPROTEIN LEVELS
Sirs: Nestel and Poyser [1] examined the relations between the cholesterol content of the atrium and plasma lipoprotein lipid concentrations in 30 men and 8 women who required surgery for coronary heart disease. Atrial cholesterol content correlated with none of the lipoprotein lipid concentrations in these patients except for a positive association with very low density lipoprotein (VLDL) cholesterol (r = +0.32, P < 0.05). In fact it can be shown that even this relation disappeared after logarithmic transformation of VLDL cholesterol to allow for its skewed distribution. Nevertheless, there was a suggestion that patients with the highest concentrations of cholesterol in atrial tissue tended to a more severe form o f atheromatous dyslipoproteinaemia than the remainder. In view o f the importance of these data I have extended the analysis, which has provided further evidence for an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentration and the cholesterol content of extra-hepatic tissues [2]. If atrial cholesterol content increases with time, b u t the rate of accumulation is influenced by plasma lipoprotein concentrations, then there is interaction between time and lipoprotein concentration. This effect can be sought b y simultaneous (multiple) regression of atrial cholesterol on time (Xl), lipoprotein concentration (X2) and the interaction term (X,, X2). In the case o f HDL cholesterol, the interaction term should be statistically significant (P < 0.05) and of negative sign in order to support the hypothesis that this lipoprotein reduces the rate of cholesterol accumulation in extra-hepatic tissues. For LDL and V L D L the interaction terms should be significant b u t positive when high concentrations increase the rate o f cholesterol accumulation. The variable factor " t i m e " requires further consideration. This is the period during which cholesterol has been accumulating in the atrium at the adult rate. Its correct estimate is important because it partly determines the value and significance o f the interaction term and thus the conclusions o f the analysis. If the process has progressed steadily from birth then " t i m e " can b e equated with age. If on the other hand the adult pattern is established only after adolescence then the factor might be say, (age--20 years). The analysis confirmed that whichever definition was used atrial cholesterol content increased with time (P < 0.001) and that the interaction term of time with H D L cholesterol was always negative. However, the interaction term failed to achieve the conventional level o f statistical significance b y a small margin when time equalled age, but did reach significance (P ~ 0.02) when the process was assumed to have
350 1.6 1,5 1,4 9 1,3
1.2 _J
oL~ 1.1 -~ 1.0 i-
0.9 0.8
40
50
60
YEARS OF ACCUMULATION (AGE -5) Fig. I . R e l a t i o n b e t w e e n a t r i a l tissue cholesterol concentration a n d y e a r s o f a c c u m u l a t i o n ( d e f i n e d as age----5 y e a r s ) a t s t a n d a r d h i g h density llpopzotein (HDL) c h o l e s t e r o l c o n c e n t r a t i o n s o f 3 0 a n d 6 0 mg/ 1 0 0 m l . D a t a are t h o s e o f Nestel and P o y s e r [ 1 ] .
c o m m e n c e d in early childhood ("time ' ' = age--5 years). When (age--20 years) was used the interaction term was highly significant (P < 0.001). The figure illustrates the case when '~years of accumulation" was assumed to be (age-5 years). This shows that in the youngest patients atrial cholesterol appeared unrelated to H D L concentration b u t that thereafter the concentration of cholesterol in the atrium increased with time to a greater extent in those with a low HDL cholesterol than in those with a high concentration. By contrast, the analysis did n o t show that these patients with a high LDL or VLDL concentration had an increased rate of accumulation of atrial cholesterol relative to that of the remainder. These results must be interpreted with caution in such a selected group, b u t appear to support another report that in hypercholesterolaemic middle-aged patients, tissue cholesterol content is inversely related to plasma HDL cholesterol concentration [2]. The findings might mean that the supposed protective effect of HDL [3] becomes detectable in this t y p e of patient only when tissue cholesterol accumulation is well established. They do not exclude an association with other lipoproteins. For example, any association of LDL cholesterol with atrial cholesterol might be more obvious during younger adulthood and weaken as age advances, as is suggested b y prospective studies o f lipoproteins and coronary heart disease [4]. Atrial cholesterol is not s y n o n y m o u s with intimal atheroma, b u t the results support the view that a high HDL might retard the rate of accumulation of cholesterol in peripheral tissues, and thereby afford some protection against (but clearly not necessarily prevent) coronary heart disease.
351
References 1 Nestel, P.J. and Poyser, A., Cholesterol content of the h u m a n atrium is related to plasma lipoprotein levels, Athezosclezosis0 30 (1978) 177. 2 Miller, N.E., Nestel, P,J. and Cilfton-Bligh, p., Relationships between plasma lipoprotein cholesterol concentrations and the pool size and metabolism of cholesterol in man, Atherosclerosis, 23 (1976) 535. 3 Miller, G.J. and Miller, N.E., Plasma high-density Hpoprotein concentration and development of ischaemic heart disease, Lancet, I (1975) 16. 4 Gofman, J.W., Young, W. and "randy, R., Ischemic heart disease, atherosclerosis, and longevity, Circulation, 34 (1966) 679.
16--18 Jamaica Boulevard, P.O. Box 164, Federation Park, Port-of-Spain, Trinidad (W.L )
George J. Miller
