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W Hague

Publications and source records attributed to W Hague.

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Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: Results from the LIPID trial.

BACKGROUND: The effect of cholesterol-lowering therapy on death from coronary heart disease in older patients with previous coronary heart disease and average cholesterol levels is uncertain. OBJECTIVE: To compare the relative and absolute effects of pravastatin on cardiovascular disease outcomes in patients with coronary heart disease who are 65 years of age or older with those in patients 31 to 64 years of age. DESIGN: Subgroup analysis of a randomized, placebo-controlled trial. SETTING: 87 centers in Australia and New Zealand. PATIENTS: 3514 patients 65 to 75 years of age, chosen from among 9014 patients with previous myocardial infarction or unstable angina and a baseline plasma cholesterol level of 4.0 to 7.0 mmol/L (155 to 271 mg/dL). INTERVENTION: Pravastatin, 40 mg/d, or placebo. MEASUREMENTS: Major cardiovascular disease events over 6 years. RESULTS: Older patients were at greater risk than younger patients (31 to 64 years of age) for death (20.6% vs. 9.8%), myocardial infarction (11.4% vs. 9.5%), unstable angina (26.7% vs. 23.2%), and stroke (6.7% vs. 3.1%) (all P < 0.001). Pravastatin reduced the risk for all cardiovascular disease events, and similar relative effects were observed in older and younger patients. In patients 65 to 75 years of age, pravastatin therapy reduced mortality by 21% (CI, 7% to 32%), death from coronary heart disease by 24% (CI, 7% to 38%), coronary heart disease death or nonfatal myocardial infarction by 22% (CI, 9% to 34%), myocardial infarction by 26% (CI, 9% to 40%), and stroke by 12% (CI, -15% to 32%). For every 1000 older patients treated over 6 years, pravastatin prevented 45 deaths, 33 myocardial infarctions, 32 unstable angina events, 34 coronary revascularization procedures, 13 strokes, or 133 major cardiovascular events, compared with 22 deaths and 107 major cardiovascular events per 1000 younger patients. Among older patients, the numbers needed to treat were 22 (CI, 17 to 36) to prevent one death from any cause, 35 (CI, 24 to 67) to prevent one death from coronary heart disease, and 21 (CI, 17 to 31) to prevent one coronary heart disease death or nonfatal myocardial infarction. CONCLUSIONS: In older patients with coronary heart disease and average or moderately elevated cholesterol levels, pravastatin therapy reduced the risk for all major cardiovascular events and all-cause mortality. Since older patients are at greater risk than younger patients for these events, the absolute benefit of treatment is significantly greater in older patients.

Adult↗

Effect of pravastatin on frequency of fracture in the LIPID study: secondary analysis of a randomised controlled trial. Long-term Intervention with Pravastatin in Ischaemic Disease.

BACKGROUND: Statins inhibit the same biochemical pathway as aminobisphosphonates, therefore these cholesterol-lowering agents may have a beneficial effect on osteoporosis. This possibility has been supported by the finding that some statins also stimulate bone formation, and by observational studies suggesting that patients using statins have higher bone densities and lower fracture rates than controls. To assess whether statins have clinically significant effects on bone, we studied the frequency of fractures in a large randomised controlled trial of these agents. METHODS: 9014 patients (17% women, median age 62 years) with ischaemic heart disease were randomly assigned pravastatin 40 mg daily or placebo and followed up for a mean of 6.0 years. Fractures were ascertained from adverse-event reports. FINDINGS: 101 patients in the placebo group were admitted to hospital for fracture compared with 107 in the pravastatin group (hazard ratio 1.05 [95% CI 0.80-1.37]). When patients with fractures not necessitating hospital admission were added, the total number of patients having a fracture was 183 in the placebo group and 175 in the pravastatin group (0.94 [0.77-1.16]). Separate analyses for women alone and for individuals aged 65 years and over gave similar results. INTERPRETATION: These findings offer no support for the hypothesis that statins have a significant effect on fracture risk. However, this study was not of an osteoporotic population, and fracture rate, although clinically important, is an insensitive index of effects on bone. Statins should not be used to prevent osteoporosis until there is evidence for their efficacy based on randomised controlled trials.

Aged↗

Effects of pravastatin in 3260 patients with unstable angina: results from the LIPID study.

BACKGROUND: The LIPID study is a major trial of secondary prevention of coronary-heart-disease events that includes hospital admission with unstable angina (as well as myocardial infarction) as a qualifying event. In this substudy of LIPID, we compared subsequent cardiovascular risks and the effects of pravastatin in patients with previous unstable angina or previous myocardial infarction. METHODS: 3260 patients diagnosed with unstable angina and 5754 with acute myocardial infarction 3-36 months previously were randomly assigned 40 mg pravastatin daily or placebo over a mean of 6.0 years. The risk reduction of a range of cardiovascular events was estimated by means of the hazard ratio in Cox's proportional hazards model. FINDINGS: Among patients assigned placebo, survival in the two diagnosis groups was similar. The relative risk reduction for mortality with pravastatin was 20.6% in the myocardial infarction group and 26.3% in the unstable angina group (p=0.55). Pravastatin significantly reduced the rates of all prespecified coronary endpoints in the myocardial infarction group. In patients with previous unstable angina, coronary heart disease mortality, total mortality, myocardial infarction, a need for coronary revascularisation, the number of admissions to hospital, and the number of days in hospital were significantly lower with pravastatin. Overall, hospital admission for unstable angina was the most common endpoint (24.6% of the placebo group; 22.3% of the pravastatin group). INTERPRETATION: Patients who have survived acute myocardial infarction or unstable angina have a similar long-term prognosis, a high occurrence of subsequent unstable angina, and benefit similarly from therapy with pravastatin.

Adult↗

Hyperinsulinemia is common in family members of women with polycystic ovary syndrome.

OBJECTIVE: To determine whether disorders of insulin secretion are common in male and female family members of subjects with polycystic ovary syndrome (PCOS). DESIGN: Family study of siblings and parents of PCOS subjects (five families). All proband cases met the criteria of polycystic ovaries (PCO) by ultrasound (US) and hyperandrogenism. SETTING: University Reproductive Medicine Unit. PATIENT(S): Family members of PCOS subjects. INTERVENTION(S): Oral glucose tolerance testing (OGTT), insulin, and lipids were measured. Clinical examination including assessment of premature baldness in men and US of ovaries in female members. MAIN OUTCOME MEASURE(S): Insulin, lipids, and clinical parameters. RESULT(S): Hyperinsulinemia (69%) and hypertriglyceridemia (56%) was common in family members as were PCO in 79% of 24 females and premature baldness in men in 88% of eight subjects. CONCLUSION(S): Hyperinsulinemia is a potential metabolic and genetic marker for subjects who may be carriers of a familial tendency for PCO.

Adolescent↗

Metabolic approaches to the subclassification of polycystic ovary syndrome.

OBJECTIVES: To examine the relationship between various hormonal and metabolic variables in a large group of women with unequivocal evidence of polycystic ovarian syndrome (PCOS) to dissect out the metabolic heterogeneity of this condition. DESIGN: Cross-sectional observational study of PCOS (n = 122) and non-PCOS (n = 26) subjects. SETTING: Reproductive medicine unit in a tertiary teaching hospital. PATIENTS: Subjects with presumed PCOS were recruited from the Reproductive Medicine and Gynaecological Clinics and later confirmed as PCOS with recognized criteria. Several other subjects were identified through recruiting reference subjects. The PCOS population consisted of 122 patients. Reference subjects were recruited from partners of male factor infertility patients in the clinics and from the general population (n = 27). INTERVENTIONS: A 75 g 2-hour oral glucose tolerance test was performed on all subjects in their midluteal phase. Blood was taken at fasting and at 30, 60, 90, and 120 minutes. MAIN OUTCOME MEASURES: Age, body mass index (BMI), waist to hip ratio, levels of integrated glucose and insulin, concentrations of maximum insulin, sex hormone-binding globulin, T, triglyceride, apolipoproteins (Apo A1, B), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDLC). RESULTS: Five clusters could be identified. They are characterized as a nonobese group, a moderately obese group, and three very obese groups. The nonobese group (n = 41, BMI = 24.1) exhibited the lowest level of integrated insulin (236.4 mIU/L or microU/mL) and concentration of serum T (5.5 nmol/L). The moderately obese group had the second lowest level of integrated insulin (497.1 mIU/L) whereas the three very obese groups (n = 15, 13, and 5, respectively) had significantly higher but different levels of integrated insulin (group 3: 850.8 mIU/L; group 4: 1,131.5 mIU/L; and group 5: 1,531.9 mIU/L), triglyceride (group 3: 1.39 mmol/L; group 4: 1.76 mmol/L; and group 5: 2.78 mmol/L [1 mmol/L = 88mg/mL]), Apo B (group 3: 1.18 g/L; group 4: 1.08 g/L; and group 5: 1.55 g/L) and LDLC (group 3: 3.81 mmol/L; group 4: 3.05 mmol/L; and group 5: 5.06 mmol/L [1 mmol/L = 38.6 mg/100 mL]). CONCLUSIONS: The metabolic heterogeneity of the PCOS population is reflected at least partly in patients' levels of insulin, lipids, and lipoproteins, dependent and independent of BMI.

Adult↗

Spironolactone in the treatment of hirsutism.

Spironolactone (100 mg) for 25 days in each menstrual cycle was assessed over 6 months for treatment of hirsutism in 35 patients. Five patients withdrew due to either nausea or polymenorrhea. the latter problem was encountered in 16 patients. Of the 30 remaining patients, 17 had a significant reduction in hair growth as assessed by Ferriman and Gallwey hair scores (p less than 0.05). The only significant change in endocrine parameters was a reduction in serum testosterone (p less than 0.05). Treatment with spironolactone alone was inferior to our previous experience with the cyproterone acetate--estrogen combination.

Female↗

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