The association of elevated plasma cortisol and early atherosclerosis as demonstrated by coronary angiography.

To study the association of plasma cortisol and coronary atherosclerosis, we elected 71 male outpatients who had coronary angiography as part of their evaluation at our facility. Forty-eight percent of the angiograms showed no evidence of coronary artery disease (CAD), 20% showed mild CAD, and 32% showed moderate to severe CAD. We found significant correlations between elevated serial morning plasma cortisols and moderate to severe coronary atherosclerosis. Using the odds ratio, we compared plasma cortisol to the major risk factors for coronary artery disease. Plasma cortisol was second only to serum cholesterol as a discriminator in our patient population between diseased and non-diseased patients. We found a significant correlation between plasma cortisol and cholesterol, blood pressure, and smoking- the three cardinal risk factors for CAD. The highest degree of correlation was found between cortisol and cholesterol. The possible significance of the association of cortisol and the major risk factors for CAD is discussed.

Cortisol and the hypercholesterolemia of pregnancy and labor.

Lipids and lipoproteins are known to increase substantially during pregnancy and to decrease rapidly after delivery. The factors responsible for the changes have not been identified, however, they could be related to changes in one or more of the endocrine hormones. Since studies relating lipid and lipoprotein changes to cortisol or estradiol concentrations have not been made, we sought to perform such a study. For this study, we measured cholesterol, HDL-C, VLDL/LDL-C, cortisol, and estradiol concentrations from early gestation through delivery in 32 normal pregnant women. During the course of pregnancy, cholesterol increased from 145 to 211 mg/dl (45%); plasma cortisol increased from 8.6 to 17.8 micrograms/dl (107%); and urinary cortisol increased from 0.10 to 0.177 microgram/mg of creatinine (72%). Further significant increases in cholesterol (256 mg/dl, P less than 0.005) and cortisol (77.6 micrograms/dl, P less than 0.001) occurred during labor, and both decreased after delivery. Pooled correlations were calculated and both cholesterol and VLDL/LDL-cholesterol concentrations were found to be related to plasma cortisol as well as to urinary cortisol (P less than 0.001). Plasma estradiol concentrations increased during pregnancy, but not during labor. The results suggest that the increases in cholesterol during pregnancy and labor could be due, in part, to the metabolic and stress-related increases in cortisol. The studies also suggest that both pregnancy and labor and delivery might be useful "natural" models for studying hormonal mechanisms involved in lipid and lipoprotein metabolism.

Relation between high density lipoprotein cholesterol and coronary artery disease in asymptomatic men.

The well established inverse relation of high density lipoprotein cholesterol (HDL) and the risk of coronary artery disease was tested in a cross-sectional group of 572 asymptomatic aircrew members who were being screened for risk of coronary artery disease. A battery of tests was performed, including determinations of fasting serum cholesterol, HDL cholesterol and triglycerides and performance of a maximal symptom-limited exercise tolerance test. Of the 572 patients, 132 also had an abnormal S-T segment response to exercise testing or were otherwise believed to have an increased risk of organic heart disease and subsequently underwent coronary angiography. Significant coronary artery disease was found in 16 men and minimal or subcritical coronary disease in 14; coronary angiograms were normal in the remaining 102 men. The remaining 440 men, who were believed to have a 1 percent chance of having coronary artery disease by sequential testing of risk factors and treadmill testing, had a mean cholesterol level of 213 mg/100 ml, a mean HDL cholesterol of 51 mg/100 ml and a mean cholesterol/HDL ratio of 4.4. The mean values of cholesterol, HDL cholesterol and cholesterol/HDL cholesterol did not differ significantly in men with normal angiographic finding and those with subcritical coronary disease. However, 14 of 16 men with coronary artery disease had a cholesterol/HDL ratio of 6.0 or more whereas only 4 men with normal coronary arteries had a ratio of 6.0 or more. Of the classical coronary risk factors evaluated, the cholesterol/HDL ratio of 6.0 or more had the highest odds ratio (172:1). It appears that determination of HDL cholesterol level helps to identify asymptomatic persons with a greater risk of having coronary artery disease.

Cholesterol, stress, lifestyle, and coronary heart disease.

Because of the recent report by the Lipid Research Group showing that a lowering of total cholesterol and LDL cholesterol lowered mortality due to coronary heart disease (CHD) and other similar studies, there can no longer be any doubt that cholesterol is a causal factor in the development of CHD. Since total serum cholesterol and LDL cholesterol are produced by the body, those interested in the prevention of CHD must give greater attention to factors which are associated with raised endogenous cholesterol. The major factors are increased dietary and body fat, emotional arousal, and the inability of the liver to clear the serum of low density lipoprotein. The beneficial effect of exercise on lowering one's risk of CHD reported in the literature may be mediated by a rise in HDL cholesterol and/or weight loss. All patients should have their total cholesterol/HDL measured. Those with elevated serum cholesterols should be encouraged to eat a low saturated low fat diet, exercise, maintain proper weight and avoid undue distress. Cigarette smoking should be discouraged. Blood pressure elevations not responsive to diet and exercise should be treated with medication. Cholesterol elevations not responsive to life style change, should be treated with Cholestyramine.

Interpretation of an abnormal oral glucose tolerance test encountered during multiphasic laboratory screening.

We have studied 162 healthy male flyers who had repeat glucose tolerance tests at intervals of 6 months to 2 years. On the premise that an abnormal oral glucose tolerance test (OGTT) was not reproducible because standard criteria were not strict enough, we evaluated 11 different criteria for diagnosing an abnormal OGTT. The number of abnormal tests varied according to the criteria but, no matter how the criteria were varied, the best reproducibility of any abnormal test on repeat testing was 50%. Factors affecting the reproducibility of an abnormal test are discussed. We conclude that a single, standard 2-h oral glucose tolerance test should be considered only as a screening test for diabetes mellitus, and that a final diagnosis of chemical diabetes mellitus should be made only if the carbohydrate in-tolerance consistently worsens or if insulin curves show hypofunction of the Islets of Langerhans. Our recommendations for followup studies of a patient with an initial abnormal OGTT are outlined. This study illustrates the importance of basic definitions of diagnostic criteria for diseases which have a long-term effect on the health of the flying population.

Predictive value of family history in detecting hypercholesterolemia in predominantly Hispanic adolescents.

Plasma levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were obtained in 110 senior high school students who were predominantly Hispanic. Results were compared with family history of premature coronary heart disease or hypercholesterolemia. The level of high-density lipoprotein cholesterol was significantly lower in Hispanic adolescents than in non-Hispanics (P less than 0.05). A positive family history was found in 22% of the subjects. Only 25% of the students with high levels of total cholesterol had a positive family history. The positive predictive value of family history for a high level of total cholesterol was only 38%. These results suggest that adolescents should be screened for hypercholesterolemia regardless of a positive family history.

Three-pool analysis for quality control: a method for daily differentiation of analytic error from random variability.

Using the Z statistic we have devised a novel, mathematically simple concept for daily quality control of laboratory procedures. The method allows rapid identification and differentiation of systematic errors from random variability on a daily basis, increases confidence in the accuracy of reported results, reduces the number of repeat analyses, and allows the analyst to detect a deteriorating quality control pool. Using three controls instead of one or two increases the chance of detecting out-of-control situations and uses simplified statistical calculations summarized on a single graphic wall chart to monitor the daily accuracy and precision of analytic procedures. The method is adaptable to any type of specimen quantitatively analyzed and can be used in large or small laboratories with light or heavy workloads. This paper reflects what happens in a small laboratory with only one run each day, but, the system has been tested in a large community hospital with a heavy workload and multiple runs each day. Although this procedure is presented for the clinical laboratory, the method would be equally useful in industry.

Relationship between cortisol and cholesterol in men with coronary artery disease and type A behavior.

To further understand the hormonal mechanisms linking behavior pattern and coronary artery disease (CAD), we investigated the relationship between 0930-hour plasma cortisol and cholesterol in relatively young males who had undergone coronary angiography and in a subgroup of individuals who had undergone the structured interview for classification of behavior pattern. A statistically significant association (p less than 0.05) was found between cortisol and cholesterol for individuals who had either minimal CAD (20% to 49% narrowing) or significant CAD (greater than or equal to 50% narrowing), but not for subjects without CAD. An association between cortisol and cholesterol was also found to be significant for the subgroup of individuals with Type A-1 behavior pattern, but not for those with Type A-2, X, or B behavior patterns. The findings suggest that hormonal mechanisms involving cortisol and cholesterol metabolism may be operative in individuals with CAD as well as in individuals with Type A-1 behavior.

Abnormal hormone levels in men with coronary artery disease.

Plasma concentrations and urinary excretions of various hormones and hormone metabolites were measured in four groups. Group 1 was composed of 13 men with prior myocardial infarction; Group 2 contained 35 clinically normal men; Group 3 consisted of 44 men with normal coronary arteriograms; and Group 4 was composed of 25 men with severe coronary artery disease shown on arteriogram but no infarction. There were four major findings: Group 1 had significantly higher 24-hour mean plasma concentrations of estrone (E1), dehydroisoandrosterone (DHA), and dehydroisoandrosterone sulfate (DHAS) than Group 2, while Group 3 had the same levels as Group 4; Group 4 had significantly lower urinary excretion of androsterone glucuronide (AG) than Group 3, while Group 1 excreted normal amounts. There are three possible explanations for these findings: 1) myocardial infarction occurring in men with coronary artery disease may elevate the plasma levels of E1, DHA, and DHAS and eliminate the preinfarction depression of urinary AG levels; 2) higher than average levels of E1, DHA, DHAS, and AG may favor the development of infarction in men with coronary artery disease; 3) higher than average levels of E1, DHA, DHAS, and AG may favor survival from any infarction that occurs in men with coronary artery disease. Experimental and epidemiological evidence seems to favor the third possibility.