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Biomedical subjects

J C Stevenson

Publications and source records attributed to J C Stevenson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Insulin resistance, lipoproteins, body fat and hemostasis in nonobese men with angina and a normal or abnormal coronary angiogram.

OBJECTIVES: The aim of this study was to compare metabolic risk factors in men with anginal chest pain and a normal or abnormal coronary angiogram with those in healthy men. BACKGROUND: Risk factors for coronary heart disease, including lipoprotein abnormalities, hypertension and adiposity, may be metabolically interlinked, with insulin resistance and hyperinsulinemia being pivotal to these disturbances. METHODS: Glucose and insulin metabolism, lipids and lipoproteins, hemostasis, blood pressure and body fat distribution were measured in 77 nonobese middle-aged men who had anginal chest pain (39 with an abnormal coronary angiogram and 38 with no detectable angiographic abnormality) and were compared with those of 40 healthy men of similar age and body mass index. RESULTS: Patients with chest pain had higher insulin responses to an intravenous glucose challenge, lower insulin sensitivity, lower high density lipoprotein (HDL) and subfraction 2 cholesterol, lower apolipoprotein AI, higher triglycerides, greater android fat and higher systolic blood pressure at rest compared with levels in healthy control subjects (p < 0.05). Those with an abnormal coronary angiogram had lower tissue plasminogen activator levels, higher plasminogen activator inhibitor 1 levels and more android fat than did those with a normal angiogram (p < 0.05). Insulin sensitivity correlated positively with HDL (p < 0.05) and subfraction 2 (p < 0.001) cholesterol and negatively with triglycerides (p < 0.01), android fat proportion (p < 0.01) and systolic blood pressure (p < 0.05), whereas insulin response showed converse correlations. CONCLUSIONS: These findings provide new evidence of the central role of insulin resistance and hyperinsulinemia in the development of risk factors associated with coronary heart disease.

Adult↗
PubMed1994

Bone density and endometriosis.

To establish whether there is evidence of low bone density in women with endometriosis, we compared bone density between 48 women with laparoscopically proven endometriosis and 48 age-matched normal controls. Bone density of the lumbar spine (L2-4), proximal femur (femoral neck, Ward's triangle, and trochanteric region), and total body were measured by dual energy roentgenogram absorptiometry. After adjusting for physical and lifestyle differences, bone density was not significantly different between the groups in any site. Bone density measurements were not related to the severity of endometriosis. These results do not confirm evidence of low bone density in women with endometriosis.

Absorptiometry, Photon↗
PubMed1994

Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: links between osteoporosis and cardiovascular disease?

The effect of spinal degenerative changes and aortic calcification on bone mineral density measurements was studied in 115 healthy early post-menopausal women. Lateral lumbar spine radiographs and quantitative computer tomography images were used to determine the presence and severity of aortic calcification and degenerative changes in the lumbar spine. Women with spinal degenerative calcification had higher spine bone density when measured by dual photon absorptiometry compared to those without calcification (P < 0.01), but this was not reflected by the quantitative computer tomography or the proximal femur bone densities, suggesting that spinal calcification artefactually increases spinal bone density when measured by dual photon techniques. Women with aortic calcification had significantly lower quantitative computer tomography and proximal femur bone density compared to those without calcification (both P < 0.05). These women may be at increased risk for both osteoporosis and cardiovascular disease, suggesting a common aetiological factor such as oestrogen deficiency.

Aortic Diseases↗
PubMed1994

Insulin resistance syndrome as a feature of cardiological syndrome X in non-obese men.

OBJECTIVE: To assess the features of the insulin resistance syndrome in patients presenting with cardiological syndrome X, who experience angina despite angiographically normal coronary arteries. PATIENTS AND METHODS: 14 Non-obese male patients with syndrome X and 38 symptom free, apparently healthy, male volunteers were studied. Insulin sensitivity (inversely related to insulin resistance) was measured by minimal modelling analysis of glucose and insulin concentrations during an intravenous glucose tolerance test. Serum lipids, lipoproteins, and apolipoproteins were also measured. RESULTS: Insulin sensitivity was 31% lower in the men with syndrome X (p < 0.05) and fasting insulin concentration was 30% higher (p < 0.05). The patient group also had 64% higher mean triglycerides (p < 0.001) and 20% lower mean high density lipoprotein cholesterol concentration (p < 0.01). Systolic blood pressure was also 10% higher in the syndrome X group (p < 0.01). There were no differences in total cholesterol, low density lipoprotein cholesterol or lipoprotein (a). CONCLUSION: These findings show that non-obese male patients with anginal chest pain but normal coronary arteries (syndrome X) are insulin resistant, hyperinsulinaemic, and have higher concentrations of triglycerides and lower high density lipoprotein cholesterol than healthy men. The insulin resistance syndrome may predispose to a spectrum of arterial disease capable of causing myocardial ischaemia.

Adult↗
PubMed1994

Hormone replacement therapy and the cardiovascular system. Nonlipid effects.

Coronary heart disease (CHD) is the leading cause of death in women, and the risk of this disease rises markedly after loss of ovarian function. Hormone replacement therapy (HRT) can reduce the incidence of CHD in postmenopausal women by 50%. HRT causes changes in lipids and lipoproteins, but it is now clear that many other effects of gonadal steroid hormones have important influences on the cardiovascular system. These nonlipid effects include a variety of changes in other metabolic risk factors for CHD, as well as direct arterial effects. Insulin resistance and hyperinsulinaemia may be pivotal disturbances in the pathogenesis of CHD. Estradiol reverses the effects of menopause on glucose and insulin metabolism, resulting in an increase in pancreatic insulin secretion and a decrease in insulin resistance, although other types of estrogen may not do this. Androgenic progestogens may oppose this potentially beneficial effect on insulin resistance. Central obesity is linked with many CHD risk factors, and HRT reverses the increased fat distribution that results from loss of ovarian function at the menopause. HRT may also improve the balance between coagulation and fibrinolysis, resulting in a reduction in arterial thrombosis. Finally, estradiol acts directly on the arterial wall, modifying both endothelium-dependent and calcium-dependent processes. These actions result in improved blood flow and reduced blood pressure and, importantly, have the potential to reduce myocardial ischaemia.

Adipose Tissue↗
PubMed1994

Long-term effects of oral and transdermal hormone replacement therapies on serum lipid and lipoprotein concentrations.

OBJECTIVE: To see whether the short-term changes in serum lipid and lipoprotein concentrations induced by postmenopausal estrogen-progestin therapy are maintained in the long term. METHODS: Sixty-one healthy postmenopausal women were randomized to either oral therapy (continuous conjugated equine estrogens at 0.625 mg/day with sequential dl-norgestrel at 0.15 mg/day for 12 days each cycle) or transdermal therapy (patches delivering continuous 17 beta-estradiol [E2] at 0.05 mg/day with sequential norethindrone acetate at 0.25 mg/day for 14 days each cycle). Twenty-nine healthy postmenopausal women who did not request therapy served as a reference group. Fasting serum lipid and lipoprotein concentrations were monitored for 3 years. RESULTS: Studied in the estrogen-progestin phase, oral and transdermal therapies reduced serum total cholesterol concentrations by 12.1% (P < .001) and 8.4% (P < .001), respectively, and those of low-density lipoprotein (LDL) by 14.2% (P < .001) and 6.6% (P < .01), respectively. These changes, apparent at 3 months, were maintained over 3 years. Serum triglyceride concentrations fell by 2.5% (P < .05) and 16.4% (P < .01), respectively. These decreases were evident after 6 months in both groups but were maintained over 3 years only in the transdermal group. High-density lipoprotein (HDL) concentrations fell in women given oral therapy (7.8%, P < .05) and transdermal therapy (10.7%, P < .001), as well as in untreated women (7.0%, P < .05). CONCLUSIONS: The potentially beneficial effects of estrogen-progestin therapy on serum total and LDL cholesterol and on triglycerides were maintained over 3 years. Interpretation of the potentially detrimental effects on HDL concentrations was hindered by the changes seen in untreated women.

Administration, Cutaneous↗
PubMed1994

HRT mechanisms of action: carbohydrates.

Elevated insulin concentrations are frequently found in both men and women with coronary heart disease (CHD), and are likely to be due to insulin resistance. Hyperinsulinaemia may increase CHD risk by directly promoting atherogenesis, and insulin propeptides may also be important in this respect. However, increased insulin concentrations may adversely affect several other CHD risk factors, and it has been postulated that insulin resistance is a pivotal metabolic disturbance in a constellation of CHD risk factors. There is an association between hyperinsulinaemia and hypertension, although it is not known if this association is direct. Increased insulin concentrations are also associated with high triglycerides, low HDL or HDL2 concentrations, and increased small dense LDL. Obesity is also associated with insulin resistance, and it is the central or android body fat distribution which correlates with these metabolic disturbances. All these associated factors constitute a distinct syndrome--the insulin resistance syndrome--which is a frequent finding in patients with CHD, including microvascular angina. It is possible that the adverse associations of insulin resistance and dyslipidaemia are mediated through increased nonesterified fatty acid flux. Increased insulin levels are also associated with increases in the anti-fibrinolytic factor, plasminogen activator inhibitor-I (PAI-I). Whilst increased insulin levels are typically associated with insulin resistance, reduced hepatic insulin uptake may also be important. We now have techniques which can quantitate insulin secretion, hepatic uptake and release, elimination, and resistance. The menopause has appreciable effect on insulin and glucose metabolism. Estrogen and progesterone augment pancreatic insulin secretion, but the former reduces insulin resistance whilst the latter increases it.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1994

Effect of continuous combined estrogen and desogestrel hormone replacement therapy on serum lipids and lipoproteins.

OBJECTIVE: To determine the effects of continuous combined hormone replacement therapy with desogestrel and 17 beta-estradiol (E2) on serum lipids and lipoproteins. METHODS: Fifty-seven healthy postmenopausal women of less than 60 years of age were studied prospectively and treated with oral desogestrel 0.15 mg/day and micronized 17 beta-E2 1 mg/day, both taken continuously. Fasting venous blood samples for serum lipids and lipoproteins were taken before and after 6 and 12 months of treatment. RESULTS: Thirty-two women completed the study. Levels of all serum lipids and lipoproteins fell significantly by 6 months and remained low at 12 months. The mean percentage reduction after 12 months of treatment was 12.8% for high-density lipoprotein (HDL) cholesterol, which largely resulted from a reduction in the HDL2 subfraction, which fell by 25.7%. The mean percentage reduction for both low-density lipoprotein (LDL) cholesterol and triglycerides was 7.7%. The median percentage reduction for lipoprotein (a) was 17.6%. CONCLUSIONS: This combination of hormone replacement therapy had profound effects on serum lipids and lipoproteins. According to current concepts, reductions in total and LDL cholesterol, triglycerides, and lipoprotein (a) may reduce cardiovascular disease risk. The reduction in HDL was unexpected, given the rise in HDL that has been demonstrated when desogestrel is combined with ethinyl estradiol in the contraceptive pill. The lowering of HDL observed in this study is undesirable and may be potentially harmful. Our results indicate that when desogestrel 0.15 mg/day is combined with micronized 17 beta-E2 1 mg/day in a continuous manner, the effects of the progestogen on HDL predominate and cause a reduction in HDL and the HDL2 subfraction.

Cholesterol, HDL↗
PubMed1993

Differences in proximal femur bone density over two centuries.

The incidence of osteoporotic hip fractures in northern Europe has been increasing over the past few decades faster than the rate adjusted for increased life expectancy. One important factor that determines osteoporotic fracture risk is bone density. The restoration of a London church, during which skeletal material dating from 1729 to 1852 was recovered, gave us the opportunity to compare the rate of bone loss in the femora of these samples with that of present-day women. The rate of bone loss, as judged by dual energy X-ray absorptiometry, was significantly greater in modern-day women than in the women from two centuries ago, both pre-menopausally (p < 0.05) and post-menopausally (p < 0.01). The difference in bone loss in the Ward's triangle region between the Spitalfields samples and present-day women remained even when the assumed age at menopause was increased to 48 years or decreased to 42 years. The results suggest that differences in rates of bone loss over two centuries may partly account for the increasing incidence of hip fracture in modern-day women. Reasons for these differences are unclear, but one factor may be a lower degree of physical activity in present-day women.

Adolescent↗
PubMed1993

Influence of age and menopause on serum lipids and lipoproteins in healthy women.

Sex hormone deficiency is associated with increased coronary heart disease (CHD) risk in women. We measured fasting serum lipids and lipoprotein concentrations in a group of 542 healthy non-obese pre- and postmenopausal women (aged 18-70 years). Ageing was associated with increased concentrations of total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein subfraction 3 (HDL3) cholesterol and triglycerides, and decreased concentrations of high density lipoprotein subfraction 2 (HDL2) cholesterol. Body mass index (BMI) was related positively to concentrations of total and LDL cholesterol. Postmenopausal women had significantly higher concentrations of total cholesterol (P < 0.001), triglycerides (P < 0.005), LDL cholesterol (P < 0.001) and high density lipoprotein subfraction 3 (HDL3) cholesterol (P < 0.001), whilst those of HDL and HDL2 cholesterol were significantly lower (P < 0.001). These differences were independent of age, BMI and other potential confounding variables. We conclude that the menopause is associated with potentially adverse changes in lipids and lipoproteins, independent of any effects of ageing. These changes may in part explain the increased incidence of coronary heart disease seen in postmenopausal women.

Adolescent↗
PubMed1993

Preliminary evaluation of a new ultrasound bone densitometer.

A new ultrasound bone densitometer has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS), broadband ultrasound attenuation (BUA), and a proprietary factor derived from SOS and BUA, termed "stiffness." Short-term precision of ultrasound measurements was 1.4% for BUA, 0.2% for SOS, and 1.5% for stiffness in healthy women, and 1.1% for BUA, 0.1% for SOS, and 1.5% for stiffness in osteopenic women. One hundred seven women underwent measurements by ultrasound, together with dual energy X-ray absorptiometry (DXA) bone mineral density (BMD) measurements of the lumbar spine and proximal femur. Correlations between SOS, BUA, and stiffness measurements and DXA BMD measurements were all highly significant (P < 0.001) with r values varying from 0.54 to 0.67. BUA, SOS, and stiffness measurements were all significantly different between normal and osteopenic women even after adjusting for age, height, and weight (P < 0.05, P < 0.001, and P < 0.01, respectively). These results demonstrate that this ultrasound system measures ultrasonic properties of the os calcis with good precision, the measurements correlate moderately well with DXA BMD measurements and they can differentiate between normals and those with osteopenia.

Absorptiometry, Photon↗
PubMed1993

A comparative metabolic study of two low-estrogen-dose oral contraceptives containing desogestrel or gestodene progestins.

OBJECTIVES: Our objective was to compare the effects of low-estrogen-dose oral contraceptives containing desogestrel or gestodene progestins on metabolic risk markers for coronary heart disease. STUDY DESIGN: A cross-sectional comparison of 70 women who used a formulation that contained 30 micrograms ethinyl estradiol and 150 micrograms desogestrel, 43 women who used a formulation that contained 30 micrograms ethinyl estradiol and 75 micrograms gestodene, and 54 women who did not use steroidal contraceptives was performed. RESULTS: Oral contraceptive users had higher concentrations of high-density lipoproteins than did women in the control group (+10% to +20%, p < 0.001) primarily because of increases in high-density lipoprotein subfraction 3. High-density lipoprotein subfraction 2 concentrations were higher in users of the desogestrel formulation. Low-density lipoprotein cholesterol concentrations were normal in oral contraceptive users, but triglyceride concentrations were high (+80% to +100%, p < 0.001). Fasting glucose, insulin, and C-peptide concentrations were similar in the three groups, but their responses to a glucose load were higher in oral contraceptive users than in controls (p < 0.01 to p < 0.001). The late plasma insulin response to glucose was higher in the women who used the gestodene formulation than in those who used the desogestrel formulation. CONCLUSIONS: The metabolic profiles induced by these oral contraceptives were remarkably similar and may reflect the activity of the estrogen component.

Adolescent↗