Alfred J. Anderson

Relation of Lipoprotein Subclasses as Measured by Proton Nuclear Magnetic Resonance Spectroscopy to Coronary Artery Disease

Although each of the major lipoprotein fractions is composed of various subclasses that may differ in atherogenicity, the importance of this heterogeneity has been difficult to ascertain owing to the labor-intensive nature of subclass measurement methods. We have recently developed a procedure, using proton nuclear magnetic resonance (NMR) spectroscopy, to simultaneously quantify levels of subclasses of very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins; subclass distributions determined with this method agree well with those derived by gradient gel electrophoresis. The objective of the current study of 158 men was to examine whether NMR-derived lipoprotein subclass levels improve the prediction of arteriographically documented coronary artery disease (CAD) when levels of lipids and lipoproteins are known. We found that a global measure of CAD severity was positively associated with levels of large VLDL and small HDL particles and inversely associated with intermediate size HDL particles; these associations were independent of age and standard lipid measurements. At comparable lipid and lipoprotein levels, for example, men with relatively high (higher than the median) levels of either small HDL or large VLDL particles were three to four times more likely to have extensive CAD than were the other men; the 27 men with high levels of both large VLDL and small HDL were 15 times more likely to have extensive CAD than were men with low levels. In contrast, adjustment for levels of triglycerides or HDL cholesterol greatly reduced the relation of small LDL particles to CAD. These findings suggest that large VLDL and small HDL particles may play important roles in the development of occlusive disease and that their measurement, which is not possible with routine lipid testing, may lead to more accurate risk assessment.

Postmenopausal use of estrogen and occlusion of coronary arteries

The degree of coronary artery occlusion was compared between users and nonusers of postmenopausal estrogen among 933 female patients undergoing angiography between the ages 50 and 75 years in the Milwaukee Cardiovascular Data Registry. Users (n = 154) had less occlusion than nonusers (n = 779), and a significant increase in occlusion scores with age was evident for nonusers (p less than 0.001) but not for users (p = 0.50). The age-adjusted odds ratios for use of postmenopausal estrogen among women with moderate and severe levels of occlusion of the coronary arteries were 0.59 (95% confidence interval, 0.48 to 0.73) and 0.37 (95% confidence interval, 0.29 to 0.46), respectively, which indicated a statistically significant, apparent protective effect of postmenopausal estrogen on coronary occlusion. This effect was independent of the type of menopause or other risk factors but not independent of high-density lipoprotein-cholesterol levels. Higher high-density lipoprotein-cholesterol levels among users may indicate a biologic mechanism by which postmenopausal estrogen use lowers the risk of coronary occlusion.

Body fat distribution and male/female differences in lipids and lipoproteins.

The role of body fat distribution, as assessed by the ratio of waist-to-hip circumferences (WHR), in statistically explaining differences in levels of lipoproteins between men and women was studied using data collected in 1985-1986 from employed adults (mean age, 40 years). As compared with the 415 women, the 709 men had higher mean levels of triglycerides (+38 mg/dl) and apolipoprotein B (+11 mg/dl) as well as lower mean levels of high density lipoprotein (HDL) cholesterol (-15 mg/dl) and apolipoprotein A-I (-19 mg/dl). Additionally, men were more overweight, consumed more alcohol, and exercised more frequently than women but were less likely to smoke cigarettes. Controlling for these characteristics, however, did not alter the differences in lipoprotein levels between men and women. In contrast, adjustment for WHR (which was greater among men) reduced the sex differences in levels of apolipoprotein B (by 98%), triglycerides (by 94%), HDL cholesterol (by 33%), and apolipoprotein A-I (by 21%). Similar results were obtained using analysis of covariance, stratification, or matching; at comparable levels of WHR, differences in lipid and lipoprotein levels between men and women were greatly reduced. Although these results are based on cross-sectional analyses of employed adults and need to be replicated in other populations, the findings emphasize the relative importance of body fat distribution. Whereas generalized obesity and body fat distribution are associated with lipid levels, fat distribution (or a characteristic influencing fat patterning) can be an important determinant of sex differences in levels of triglycerides, HDL cholesterol, and apolipoproteins B and A-I.

Body fat distribution, plasma lipids, and lipoproteins.

The relation of body fat distribution as measured by the ratio of waist to hip circumferences (WHR) to plasma levels of lipids and lipoproteins was studied In 713 men and 520 women who were employed by two Milwaukee companies. Quetelet Index (kg/m2), waist girth, hip girth, and WHR were each positively related to levels of total cholesterol, trlglycerldes, apollpoproteln B, and the ratio of total to high density llpoproteln (HDL) cholesterol. In addition, the anthropometrlc measures were Inversely associated with levels of HDL cholesterol. (Controlling for age, alcohol intake, exercise level, current smoking status, and oral contraceptive use only slightly reduced the strength of the correlations.) In addition, WHR and Quetelet Index were Independently related to llpld and llpoproteln levels, and the magnitudes of the associations were roughly equivalent For example, the mean (covarlate-adjusted) trlglycerlde level among men In the upper tortile of the Quetelet Index was 37 mg/dl higher than for men in the lower tertlle of the Quetelet Index; the corresponding difference according to WHR tertlles (upper to lower) was 39 mg/dl (p<0.01 for both effects). These findings Indicate that In healthy men and women a less favorable lipid and llpoproteln profile Is associated with elevated levels of both Quetelet Index and WHR.

Effects of drinking patterns on the relationship between alcohol and coronary occlusion

Previous reports have described an inverse relationship between alcohol consumption and the prevalence of myocardial infarction or the extent of coronary artery occlusion. The study reported here explored the relationship between patterns of alcohol intake and coronary occlusion in 526 patients who have had coronary arteriography. Patients were characterized as regular drinkers, occasional drinkers and non-drinkers. Regular drinkers were further characterized as drinking relatively consistent amounts or variable amounts. The inverse correlation between amounts of alcohol consumed and coronary occlusion found in previous studies was reaffirmed. It was also observed that the pattern of alcohol intake was related to the degree of occlusion. Higher levels of occlusion were found among non-drinkers, occasional drinkers, and regular drinkers with patterns of variable intake, while significantly lower levels of occlusion were observed for regular drinkers who drank relatively consistent amounts (P = 0.014). Furthermore, while occlusion scores were inversely correlated with amounts consumed by regular drinkers with consistent intake (P = 0.019), drinkers with variable drinking patterns had higher occlusion scores regardless of amounts consumed. Analyses of serum lipids according to drinking patterns showed a significant association between the total/HDL cholesterol ratio and drinking patterns. These findings suggest that whatever attenuating effect alcohol consumption might exert on coronary occlusion, it appears to be reversed by a variable or sporadic pattern of alcohol intake.

The Association of Smoking with Cardiomyopathy

We investigated the possibility that smoking has an association with ventricular wall-motion abnormalities that is independent of its known association with coronary occlusion. We studied 4763 men between the ages of 35 and 74 who had diagnostic coronary angiography and ventriculography. We considered three kinds of wall-motion abnormalities: hypokinesis in one to four ventricular segments, hypokinesis in five to six ventricular segments (diffuse hypokinesis), and akinetic or dyskinetic wall motion in at least one segment. Among men younger than 55, the relative risk of diffuse hypokinesis was 2.78 (1.1 to 6.99) for heavy smokers as compared with nonsmokers. Adjusting for the degree of coronary occlusion or eliminating subjects with a history of myocardial infarction did not change this relative risk. Among men who were 55 or older the relative risk (odds ratio for heavy smokers as compared with nonsmokers) was not significant (0.55 to 2.28). Regardless of age the relative risk of akinesis or dyskinesis, adjusted for coronary stenosis, was significant: 1.84 (1.28 to 2.65) for men under 55 and 1.57 (1.12 to 2.19) for men 55 or older. These results suggest that smoking is related to both cardiomyopathy and transmural myocardial infarction and that the relationships are largely separate from the association of smoking with coronary stenosis.

Importance of white blood cells in platelet storage.

Abstract. Platelet concentrates from 290 healthy donors collected in CPD anticoagulant and PL‐146 polyvinylchloride containers were stored for 72 h at 22±0.5°C under standard conditions to investigate variables affecting the quality of stored platelets. In addition to the expected inverse relationship between pH and platelet count (p < 0.001), a significant inverse correlation between pH and white blood cell count (WBC) was also noted (p < 0.01). Platelets from female donors developed a lower pH than those from male donors; this difference could not be accounted for by any of the variables analyzed other than sex. To investigate the relationship between WBC and pH further, 15 units of platelet‐rich plasma (PRP) were depleted of WBCs by slow centrifugation prior to being stored for 3 days. This resulted in a mean loss of 10% of the platelets and 75% of the WBCs. The average post‐storage pH of the 15 WBC‐poor concentrates (7.06 ± 0.02) was significantly higher than that of routinely prepared concentrates containing the same number of platelets (6.54 ± 0.43) (p < 0.001). Production of lactic acid and consumption of glucose was markedly diminished in leukocyte‐poor concentrates. These data suggest that WBCs significantly affect the metabolic activity of platelet concentrates and that the quality of stored platelets can be improved by reducing the number of contaminating leukocytes. Measurement of leukocytes may be important in quality control of platelet concentrates.

High density lipoprotein cholesterol and coronary artery occlusion.

The relationship between the levels of high density lipoprotein cholesterol (HDLC) and the extent of coronary artery occlusion (ascertained by arteriography) was studied in four hundred male patients. The group with HDLC levels over 50 mg/dl showed a significantly lower coronary artery occlusion score and lower plasma triglyceride levels than the patients with HDLC levels less than 35 mg/dl. The former group also imbibed more alcohol and had less smoking experience.

Results of Intraaortic Balloon Pumping after Cardiac Surgery: Experience with the Percor Balloon Catheter

One hundred thirty-eight patients undergoing an open-heart procedure required an intraaortic balloon pump (IAPB) postoperatively. In Group I (N = 45), the AVCO femoral conduit surgical technique was used; in Group II (N = 93), the Percor balloon was inserted either in the operating room after groin cutdown (open insertion) or percutaneously in the intensive care unit (percutaneous insertion). IABP usage increased in Group II (3% versus 1.6%; p less than 0.001). Immediate mortality was 40% (55/138). Use of the Percor balloon in Group II resulted in lower immediate mortality (32/93 or 34% versus 23/45 or 51%; p less than 0.06). Delayed mortality from multiorgan failure was 11.6% (16/138). Immediate percutaneous insertion at the bedside rather than a return to the operating room for open insertion yielded lower mortality (2/8 or 25% versus 6/7 or 86%; p less than 0.05). Open insertion of the Percor balloon decreases the failure rate of insertion compared with both the AVCO femoral conduit technique (7/85 or 8.2% versus 5/45 or 11%) and percutaneous insertion. It has more complications than the AVCO femoral conduit technique (7/85 or 8.2% versus 2/45 or 4.4%) and less than percutaneous insertion.

Long-Term Follow-up of the Björk-Shiley Prosthetic Valve Used in the Mitral Position

Abstract This study analyzes 547 patients who had mitral valve replacement with a Bjork-Shiley prosthesis over a 9-year period (mean follow-up, 46.5 months). Operative mortality was 7.3%, and 5-year survival was 76.9%. Serious anticoagulation problems occurred in 1.8% (10 patients) and serious thromboembolic episodes in 5.3% (28 patients) (1.3 per 1,000 patient-months). The study includes 257 patients with isolated mitral valve replacement (Group 1) and 290 who had associated procedures (Groups 2 through 5). Hospital mortality in Group 1 was 2.7% compared with 11.7% in Groups 2 through 5 ( p p In the patients in Group 1 with pure mitral insufficiency (MI), 5-year survival was 70.9%, significantly lower ( p Significantly lower ( p