H. P. Chin

Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts. Lipid and nonlipid factors.

A within-group risk factor analysis was conducted to predict angiographic change in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled trial of colestipol plus niacin therapy in men with previous coronary bypass surgery. Global angiographic change, including both native coronary arteries and bypass grafts after 2 treatment years, was the end point. Risk factors included on-trial clinical measures, plasma lipids, lipoproteins, and apolipoproteins. Univariate analysis indicated that risk factors previously observed by others in epidemiologic investigation of ischemic heart disease--total cholesterol, LDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein B, and diastolic blood pressure--had significant effects in the placebo-treated group. Univariate analysis indicated significant effects of apolipoprotein C-III in drug- and placebo-treated groups. Multivariate analysis indicated the predominant risk factor predicting the probability of global coronary progression was non-HDL cholesterol in placebo-treated subjects and the content of apolipoprotein C-III in high density lipoproteins of drug-treated subjects. Both drug- and placebo-treated group findings point to an important role for triglyceride-rich lipoproteins in progression and regression of human atherosclerosis.

Separation and quantitative analysis of serum lipoproteins by means of electrophoresis on cellulose acetate

Abstract A method for lipoprotein electrophoresis on cellulose acetate is described. Features which distinguish this method are: (1) It affords complete resolution of chylomicrons, β-lipoproteins, pre-β-lipoproteins, and α-lipoproteins into distinct bands and allows the relative magnitude of each to be estimated by transmission microden-sitometry. (2) Lipoproteins can be eluted quantitatively from separated bands for analyses. (3) Intact chylomicrons can be recovered by ultrasonic treatment. (4) The procedure is rapid, reproducible, and does not require addition of albumin to the buffer.

Design of human atherosclerosis studies by serial angiography.

Atherosclerosis has been studied by femoral angiography in men with myocardial infarction. Smoking history recorded at entry was the strongest variable asssociated with degree of atherosclerosis at the first angiogram. This correlation was significant at the 1% level in two out of three femoral segments. Fifty-four men had two angiograms; 28 of these men had one additional angiogram. Two variables recorded in the interval between angiograms were significantly correlated with atherosclerosis change in one femoral segment; α-lipoprotein level determined by electrophoresis (a negative correlation, p < 0.01) and maximum systolic blood pressure occurring during an exercise tolerance test (a positive correlation, p < 0.01). An estimate of angiographic atherosclerosis assessment error has been obtained (S.D. = 8.28; in a scale of 1–128) and used to calculate sample size for future clinical trials which employ this endpoint. Testing the effect of therapy on lesion change with angiography requires fewer study subjects observed for a shorter period than is necessary to test a commensurate effect on atherosclerosis-related morbidity or mortality rates. For example, an angiographic study with design features comparable to those of the Coronary Drug Project could require a 1-yr observation period and 132 subjects per test group.

Assessment of Atherosclerosis from Angiographic Images

Summary Raised aortic atheromas can be quantitated by densitometer-computer analysis of edge irregularity on angiographic shadows. Combined measurement of edge irregularity and variation in cross-sectional density provides an angiographic index indicative of local cholesterol concentration in aorta walls and atheromas.

Lipids in Silicone Rubber Valve Prostheses After Human Implantation

Fourteen prosthetic valves were obtained from human recipients at autopsy or valve replacement surgery. The silicone rubber poppets were extracted with lipid solvent and examined by thin-layer chromatography, infrared absorption spectroscopy, and phosphorus analysis. The significant findings were: (1) No phospholipid was present in any of the valves; neither was there any protein. (2) The relative content of cholesterol, cholesteryl ester, fatty acid, and triglyceride varied widely. (3) Residual uncured silicone polymers were found in all valves; in one patient these appeared to combine with lipid and form a component with unusual chromatographic behavior.

Ultrasound observation on pulsation in human carotid artery lesions

B-mode ultrasound imaging was used to compare pulsation in moderately advanced, non-calcific, common carotid atherosclerotic lesions with adjacent carotid artery walls where no lesions were visible. Subjects were 13 men with proven coronary atherosclerosis. Average age was 54 years and subjects did not have cerebral symptoms or carotid bruits. Ep, the pressure-strain modulus, was estimated using brachial artery blood pressures recorded on the same clinic visit. Ep values in lesion areas were significantly greater than in nonlesion areas. Two extremely high Ep lesion values were found which could not be explained on the basis of focal calcification as determined by ultrasonic or angiographic images. Study of lesion pulsation by ultrasound imaging is proposed as a new noninvasive procedure for characterizing human carotid atherosclerosis.

Prediction of Lipid Uptake by Prosthetic Heart Valve Poppets from Solubility Parameters

Most prosthetic heart valves currently implanted consist of a silicone rubber poppet situated within a metallic cage. Recent reports indicate that gradual deterioration of the poppet can occur and lead to serious valve malfunction. Physical changes (variance) observed in recovered prosthesis include discoloration, swelling, and cracking. A major cause of variance is believed to be lipid accumulation. This article presents an assessment of the solubility of lipids in silicone rubber and other commonly used poppet materials. The analysis is based on solubility parameter theory that is based on principles derived from thermodynamic considerations. The results of this analysis predict that highly polar compounds, such as phospholipids or proteins, should not be present in silicone rubber poppets, which is in agreement with observations.

Alterations in Serum Thyroid Hormonal Indices with Colestipol-Niacin Therapy

A serial blood-lipid-lowering study at the University of Southern California yielded unexpected findings on routine thyroid function monitoring. After 1 year of combined colestipol and niacin therapy, patients had reduced total serum thyroxine (T4) levels and increased triiodothyronine uptake ratios, an indicator of apparent decreases in thyroxine-binding globulin levels. Calculation of the free T4 index partially but not completely corrected for the apparent decrease in thyroxine-binding globulin, as determined by a relatively small decrease in the free T4 index compared with a large decrease in T4. Sequential sampling, using three separate methods, showed reduced thyroxine-binding globulin levels. The mechanism for these changes is unknown, but the fact that these patients were essentially euthyroid needs emphasis because the use of combined colestipol and niacin therapy is becoming more widespread.

An improved method for determination of serum and plasma triglycerides

Abstract A method is described for the determination of serum or plasma glyceride content. The method is a modification of that described by Blankenhorn et al. Lipids are extracted with a mixture of acetone-ethanol and triglycerides separated from phospholipids by means of Florisil chromatography. The major modifications are: (1) conditioning the Florisil columns with eluting solvent to avoid the necessity for adjusting the moisture content of Florisil; (2) removal of cholesterol and fatty acids from the saponified mixtures by partitioning with petroleum ether. These two modifications bring about a significant improvement in accuracy and precision of triglyceride analyses.

Altered partition of serum cholesterol and cholesteryl ester in a petroleum ether-ethanol-water system after incubation.

D IFFERENTIAL PARTITION Of f ree and es te r ified choles te ro l be t w een aqueous e t h a n o l and p e t r o l e u m e t h e r h a s been used f o r quan t i t a t i v e ana lys i s o f se rum lipids. U n d e r t he cond i t ions of Ga lanos et al. (1) f ree cholest e ro l a p p e a r s in the aqueous e t hano l p h a s e a n d es ter i f ied choles te ro l in the p e t r o l e u m e t h e r phase. I n con t ras t , we h a v e obse rved condit ions u n d e r which f ree cho les te ro l p a r t i t i o n s in to the p e t r o l e u m e t h e r phase whi le es te r i fled choles te ro l r e m a i n s in the aqueous e t hano l phase . A modi f ica t ion of the cond i t ions resul ts in b o t h f ree and es ter i f ied cho les te ro l a p p e a r i n g in the pe t ro l eum e t h e r phase . These obse rva t i ons serve as the bas i s f o r a d d i t i o n a l a n a l y t i c a l p rocedures . The cond i t ions a re desc r ibed below. A c e t o n e e t h a n o l 1 : 1 l ip id e x t r a c t s of h u m a n se rum were p r e p a r e d as descr ibed by B l a n k e n h o r n et al. (2) . E x t r a c t s (10 ml) were dr ied , d issolved in 5 ml of abso lu te e t hano l a n d inc u b a t e d a t 37C fo r 60 rain. A f t e r i n c u b a t i o n 5 ml of de ionized w a t e r were added and the aqueous e thano l n i i x tu r e was t hen e x t r a c t e d w i t h 10 Inl of p e t r o l e u m e t h e r (bp 60C-75C) . Al l of the f ree choles te ro l ( d e t e r m i n e d b y nieans of the L i e b e r m a n n B u r c h a r d reac t ion) was f o u n d to be p r e s e n t in the p e t r o l e u m e t h e r phase a f t e r a s ingle p a r t i t i o n ; es ter i f ied choles tero l r e m a i n e d in the aqueous e t h a n o l phase . W h e n i n c u b a t i o n was om i t t ed b o t h f ree a n d ester i f ied choles te ro l a p p e a r e d in the pe t ro l eum e t h e r phase in keep i ng w i th the p a r t i t i o n coefficients of the pu re subs t ances in the solven t sys tem. Va lues fo r t o t a l f ree cho les te ro l (Tab le I ) o b t a i n e d b y t h e s o l v e n t p a r t i t i o n m e t h o d showed close a g r e e m e n t w i t h those o b t a i n e d b y t h e d i g i t o n i d e p r e c i p i t a t i o n m e t h o d o f