Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina: lack of effect of oral L-arginine on endothelial function, oxidative stress and exercise performance.

OBJECTIVES: This study was designed to determine the effect of two weeks' treatment with L-arginine on the ratio of plasma L-arginine to asymmetric dimethylarginine (ADMA), oxidative stress, endothelium-dependent vasodilatation to acetylcholine, exercise performance and heart rate variability in men with stable angina. BACKGROUND: The ratio of plasma L-arginine:ADMA has been proposed as a determinant of endothelium-dependent dilation; dietary supplementation with L-arginine has been shown to improve endothelium-dependent vasodilation and symptoms in some conditions. METHODS: Men (n = 40) with stable angina, at least one epicardial coronary artery with a stenosis >50% and a positive exercise test were randomized to receive L-arginine (15 g daily) or placebo for two weeks according to a double-blind parallel-group design. Plasma L-arginine, ADMA, 8-epi-prostaglandin F2alpha (a marker of oxidative stress) and forearm vasodilator responses to brachial artery infusion of nitroprusside and acetylcholine (+/-L-arginine) were measured. A standard Bruce protocol exercise test was performed before and at the end of the treatment period. RESULTS: Plasma L-arginine increased after oral L-arginine, whereas ADMA remained unchanged, leading to an increase in the L-arginine/ADMA ratio of 62 +/- 11% (mean +/- SE, p < 0.01). Despite a significant enhancement in acetylcholine response by intra-arterial L-arginine at baseline, this response remained unchanged after oral L-arginine. Measures of oxidative stress and exercise performance after L-arginine/placebo were similar in placebo and active groups. CONCLUSIONS: In men with stable angina, an increase in plasma L-arginine/ADMA ratio after two weeks' oral supplementation with L-arginine is not associated with an improvement in endothelium-dependent vasodilatation, oxidative stress or exercise performance.

Does angina vary with the menstrual cycle in women with premenopausal coronary artery disease?

OBJECTIVE: To determine whether angina in women with established coronary heart disease varies with changes in hormone concentrations during the menstrual cycle. DESIGN: Subjects were prospectively studied once a week for four weeks. SETTING: Cardiology outpatient department of tertiary referral centre. SUBJECTS: Nine premenopausal women, mean (SEM) age 38.89 (2.18) years, with established coronary heart disease, symptomatic angina, and a positive exercise test. MAIN OUTCOME MEASURE: Myocardial ischaemia as determined by time to 1 mm ST depression during symptom limited exercise testing. Position in the menstrual cycle was established from hormone concentrations. RESULTS: The early follicular phase, when oestradiol and progesterone concentrations were both low, was associated with the worst exercise performance in terms of time to onset of myocardial ischaemia, at 290 (79) seconds; the best performance (418 (71) seconds) was when oestrogen concentrations were highest in the mid-cycle (p < 0.05). Similar trends were observed in other measured variables. Progesterone concentrations did not influence exercise performance. CONCLUSIONS: During the menstrual cycle myocardial ischaemia was more easily induced when oestrogen concentrations were low. This may be important for timing the assessment and evaluating treatment in women with coronary heart disease.

Are women discriminated against for lipid lowering therapy? Results from a prospective cohort of women with coronary artery disease.

The objective of the study was to compare the lipid management of men and women with documented coronary artery disease in 587 patients (433 men and 154 women) undergoing coronary angiography between 1991 and 1995. A fasting total cholesterol (TC) was measured in all patients on the morning of angiography. A postal/telephone follow-up was carried out one year after angiography in a subpopulation of 278 patients (194 men and 84 women) who were not taking lipid-lowering therapy (LLT) or whose TC was > 5.2 mmol/l at the time of angiography. At baseline, mean TC was 5.89 mmol/l (SE 0.06) in the men and 6.47 mmol/l (SE 0.09) in the women (p = < 0.0001). Action or recommendation to institute LLT was taken in 141 (32.7%) men and 62 (40.3%) women (p = 0.09). In the follow-up population, comparing men with women, 74 (38.3%) vs 39 (46.4%) were taking LLT (p = 0.21); 56 (28.9%) vs 26 (31.0%) had not undergone repeat TC testing (p = 0.73); when performed, repeat TC was 5.75 (0.09) mmol/l vs 5.64 (0.16) mmol/l (p = 0.53); mean decrease in TC between baseline and follow-up was 0.86 (0.10) mmol/l vs 1.01 (0.21) mmol/l (p = 0.51). There was no significant gender difference in lipid management either at the time of coronary angiography or subsequent follow-up, although the level of lipid-lowering drug use remained inadequate in both sexes.

A randomised placebo controlled trial of the effects of tibolone on blood pressure and lipids in hypertensive women.

The effects of hormone replacement therapy in hypertensive women are controversial. This randomised placebo controlled trial assessed the effect of tibolone 2.5 mg on blood pressure and fasting plasma lipids in 29 hypertensive postmenopausal women over 6 months using a 2:1 randomisation to tibolone. The primary clinical end-point was mean office blood pressure. At 6 months systolic blood pressure declined by 5.30 +/- 2.87% vs 4.94 +/- 3.37% whilst diastolic blood pressure declined 5.38 +/- 2.65% vs 0.85 +/- 3.69% on tibolone and placebo respectively. These differences were not statistically significant. Triglycerides decreased by 33.3 +/- 6.1% vs 7.6 +/- 7.9% (P < 0.01) and high-density lipoprotein (HDL)-cholesterol by 21.7 +/- 3.8% vs 2.4 +/- 2.6% (P < 0.01) with tibolone as opposed to placebo. No significant differences were observed in total cholesterol, low-density lipoprotein (LDL)-cholesterol and lipoprotein (a). Fibrinogen levels were reduced by 13.6 +/- 6.8% on tibolone compared to a 19.3 +/- 15.4% rise (P < 0.05) on placebo. This study suggests that tibolone has no deleterious effect on blood pressure in women with hypertension but has contrasting effects on biochemical risk factors. Large-scale studies are required to determine the overall effect of tibolone on cardiovascular morbidity and mortality.

Acute effects of hormone replacement with tibolone on myocardial ischaemia in women with angina.

This study was designed to evaluate whether hormone replacement therapy with tibolone demonstrated similar effects to those observed with oestrogen on myocardial ischaemia and angina. Ten postmenopausal women with documented coronary artery disease were evaluated by treadmill exercise electrocardiograms before and 24 hours after the oral administration of tibolone 2.5 mg. Onset of myocardial ischemia, as defined by ST segment depression, increased by a median 102 seconds (p = 0.022). Time to onset of angina increased by 31 seconds (p = 0.038), while total exercise time was not significantly affected (p = 0.24). Haemodynamic variables in the form of heart rate, systolic blood pressure and their product were unaffected by tibolone administration. We conclude that tibolone appears to show similar anti-ischaemic properties to oestrogen.