Beverly Strisower

Blood Lipids and Human Atherosclerosis

The transport of cholesterol and other lipids of serum is almost wholly in the form of very large molecular complexes of these lipids with variable amounts of protein. The exact components present in the blood of a particular individual may be quantitatively described both as to character and concentration by ultracentrifugal flotation of these components in the analytic ultracentrifuge. With this technic it is possible to demonstrate the presence of certain lipid and lipoprotein components which are related to coronary atherosclerosis, to hypertension and to other diseases associated with atherosclerosis, such as diabetes mellitus, the nephrotic syndrome and hypothyroidism. The blood level of these components may be influenced by dietary means. The blood level of these components is poorly correlated with the analytic serum cholestrol determined by the Schoenheimer-Sperry method.

Lipoproteins in atherosclerosis

Abstract 1.1. Serum lipoprotein patterns as studied ultracentrifugally in the human indicate lipoprotein transport may be interpreted as reflecting varying degrees of a lipid metabolic error. 2.2. The nature of several lipid transport disturbances have been described for a variety of experimental procedures in the rabbit. In all disturbances there is a strong positive correlation between elevation of the S f 10–30 class of lipoproteins and the rate of development of atherosclerosis. Lipoproteins of the classes of S f 10 and less and S f 40–50 and higher do not show this correlation. Total serum cholesterol is positively related to the development of atherosclerosis only in those experimental procedures which allow for the increased serum cholesterol to be largely in the S f 10–30 class. 3.3. A critical comparison has been made, in which the analysis of total cholesterol and S f 12–20 lipoproteins was done on aliquots of the same serum sample, of both levels in normals vs. atherosclerotics, using myocardial infarctions as the test group. The over-all correlation of S f 12–20 lipoprotein levels with atherosclerosis is two to four times as great as that for serum cholesterol levels with atherosclerosis. 4.4. The S f 12–20 lipoprotein levels are associated with atherosclerosis, independently of their relationship with serum cholesterol. The S f 12–20 levels account for the bulk of the over-all predictive segregation of atherosclerotics from normals. 5.5. The serum cholesterol level is very much less, if at all, associated with atherosclerosis, when considered independently of its association with the S f 12–20 levels. 6.6. One-year follow-up studies of patients with coronary artery disease indicate that early recurrence of myocardial infarction is significantly associated with elevated S f 12–20 lipoprotein levels. An approximate estimate of recurrence rate as a function of S f 12–20 level may be made from the data on thirty-nine recurrences in the follow-up study. At 50 mg. per cent S f 12–20 the chance of recurrence is ~6 per cent in one year; at 110 mg. per cent the chance is ~18 per cent. 7.7. In acute myocardial infarction the prognosis for survival is worsened with highly elevated S f 12–20 lipoprotein levels, as determined during the acute phase. 8.8. Follow-up studies show that the reduction of S f 12–20 lipoprotein levels by dietary restriction of fats and cholesterol gives a significant degree of protection against recurrent myocardial infarction in patients with coronary artery disease whose levels before dietary restriction ranged above 80 mg. per cent. 9.9. The only pharmacologic agent which rapidly shifts the lipoprotein pattern in humans in the direction of normality is parenteral heparin. The possibility is considered that a deficiency of heparin or a heparin-like substance may be involved in causing the basic lipid metabolic defect in humans.

Lipoproteins and atherosclerosis.

Author(s): Gofman, John W.; Lindgren, Frank T.; Jones, Hardin B.; Lyon, Thomas P.; Strisower, Beverly.

Treatment of hyperlipidemias

Abstract The long-term effects of ethyl chlorophenoxyisobutyrate (CPIB), thyroid-active substances and diet were observed in seventy-two patients with five different types of hyperlipoproteinemias. Essential hypercholesterolemia (Sf 0–20 hyperlipoproteinemia) with tendon xanthomatosis proved refractory to CPIB, and to supplementary corn oil, but Sf 0–20 concentrations were reduced slightly (up to 20 per cent) by thyroid-active substances. Sf 0–20 hyperlipoproteinemia without tendon xanthomatosis was moderately reduced by CPIB or thyroid-active substances. In xanthoma tuberosum (characterized by very low Sf 0–12 and high Sf 12–400 lipoprotein concentrations), lipoprotein concentrations decreased to normal levels with severe carbohydrate restriction or (more acceptable to patients) CPIB therapy. In Sf 20–400 hyperlipoproteinemia, CPIB greatly reduced very low density lipoprotein, cholesterol and triglyceride levels but in 80 per cent of patients Sf 0–20 concentrations rose concurrently. In view of the atherogenicity of Sf 0–20 lipoproteins, if Sf 0–20 lipoprotein concentrations rise to high levels CPIB therapy should be discontinued. Carbohydrate restriction caused no consistent similar shift and appeared preferable to CPIB in this group. In combined Sf 0–20, Sf 20–400 hyperlipoproteinemia, CPIB reliably reduced Sf 20–400 levels; in some patients it decreased, and in some it increased Sf 0–20 concentrations; when increases occurred, added thyroid sometimes proved helpful.

Tyrosine, Iodide, and Human Serum Lipoproteins.

Conclusions and Summary 1) Tyrosine and potassium iodide do not have any effect on serum lipoprotein and total serum cholesterol concentrations. 2) These findings indicate that in clinically euthyroid patients neither substance appears to be a limiting factor in thyroidal synthesis of thyroid hormones from tyrosine and iodide.