Prior cytomegalovirus infection and the risk of restenosis after percutaneous transluminal coronary balloon angioplasty.

BACKGROUND: Restenosis is a common problem after all revascularization procedures in atherosclerotic coronary arteries. Reactivated human cytomegalovirus (CMV) has been detected in tissues of restenotic vascular lesions and was hypothesized to be a contributing pathogenic factor. Recent data suggest an association of restenosis after optimal coronary atherectomy with CMV serostatus, and a possible role of antiviral therapy was discussed. We therefore tested the hypothesis that prior CMV infection might be a risk factor for restenosis after conventional coronary balloon angioplasty (PTCA). METHODS AND RESULTS: We analyzed 92 consecutive patients who had been admitted for control angiography after previous PTCA within a mean interval of 6 months. Anti-CMV antibodies were measured as an indicator of prior CMV infection and latency. The coronary angiograms before PTCA, directly after, and 6 months later were analyzed quantitatively. Sixty-five percent of the patients were CMV-positive. Before PTCA, the degree (mean+/-SD) of stenosis was 69+/-10% in CMV-positive and 68+/-8.3% in CMV-negative subjects. PTCA resulted in a residual stenosis of 39% in both groups. After 6 months, the late losses of luminal diameter in the CMV-positive and -negative groups were 11+/-13% and 12+/-15%, respectively (P=0.658). In an ANCOVA with 25 potential risk factors for restenosis, CMV serostatus was not significantly associated with restenosis development. CONCLUSIONS: Our data indicate that prior CMV infection, in contrast to optimal atherectomy, is not associated with chronic restenosis after conventional coronary balloon angioplasty. The results do not support a possible benefit from antiviral therapy.

Responsiveness of plasma 2- and 4-hydroxycatecholestrogens to training and to graduate submaximal and maximal exercise in an untrained woman. Interuniversity Project on Reproductive Endocrinology in Women and Exercise.

A single-subject experimental design was used to obtain some preliminary findings on the plasma responses of catecholestrogens (CE) to acute exercise and brief, but exhaustive training on a cycle ergometer. One previously untrained eumenorrheic female (body fat: 26% VO2max: 43.3 ml x kg(-1) x min[-1]) participated in this study. Resting CE levels were for "total" (unconjugated + conjugated) 2-hydroxyestrogens (2-OHE) 162pg/ ml and 350 pg/ml in the follicular (FPh) and luteal phase (LPh), respectively. Plasma total 4-hydroxyestrogen (4-OHE) levels were 41 pg/ml in the FPh and 66 pg/ml in the LPh. For "total" 2-methoxyestrogens (2-MeOE), we found 257 pgl/ml in the FPh and 374 pg/ml in the LPh. Resting levels of 2-hydroxy CE following a period of brief, intensive training were decreased during the LPh (2-OHE: -38%; 2-MeOE: -19%), whereas 4-hydroxy CE were unaffected. After training, the formation of CE as expressed by the 2-OHE:E and 4-OHE:E ratios, was increased by 75% and 200% at rest, respectively. CE activity or O-methylation, as estimated from the 2-MeOE:2-OHE ratio, was higher following training (FPh: +22%; LPh: +30%). During acute exercise before training, we observed a small rise proportional to the exercise intensity in the plasma "total" primary estrogen concentrations (FPh: +28%; LPh: +16%), and no changes in either 2-OHE or 2 MeOE levels. Plasma concentrations of 4-OHE, however, doubled during maximal exercise intensity. The 2-OHE:E and 2-MeOE:2-OHE ratios did not alter during incremental exercise. Training effects on acute exercise responses were only noticed for 4-OHE, which contrary to pre-training conditions, now progressively decreased. The major findings of this study are that in response to training: a) during rest, a greater proportion of CE are formed from a lower amount of precursor hormone, b) the rate of O-methylation of CE increases.

Responses of catecholestrogen metabolism to acute graded exercise in normal menstruating women before and after training.

It has been hypothesized that exercise-related hypo-estrogenemia occurs as a consequence of increased competition of catecholestrogens (CE) for catechol-O-methyltransferase (COMT). This may result in higher norepinephrine (NE) concentrations, which could interfere with normal gonadotropin pulsatility. The present study investigates the effects of training on CE responses to acute exercise stress. Nine untrained eumenorrheic women (mean percentage of body fat +/-SD: 24.8 +/- 3.1%) volunteered for an intensive 5-day training program. Resting, submaximal, and maximal (tmax) exercise plasma CE, estrogen, and catecholamine responses were determined pre- and post training in both the follicular (FPh) and luteal phase (LPh). Acute exercise stress increased total primary estrogens (E) but had little effect on total 2-hydroxyestrogens (2-OHE) and 2-hydroxyestrogen-monomethylethers (2-MeOE) (= O-methylated CE after competition for catechol-O-methyltransferase). This pattern was not significantly changed by training. However, posttraining LPh mean (+/-SE) plasma E, 2-OHE, and 2-MeOE concentrations were significantly lower (P < 0.05) at each exercise intensity (for 2-OHE: 332 +/- 47 vs. 422 +/- 57 pg/mL at tmax; for 2-MeOE: 317 +/- 26 vs. 354 +/- 34 pg/mL at tmax). Training produced opposite effects on 2-OHE:E ratios (an estimation of CE formation) during acute exercise in the FPh (reduction) and LPh (increase). The 2-MeOE:2-OHE ratio (an estimation of CE activity) showed significantly higher values at tmax in both menstrual phases after training (FPh: +11%; LPh: +23%; P < 0.05). After training, NE values were significantly higher (P < 0.05). The major findings of this study were that: training lowers absolute concentrations of plasma estrogens and CE; the acute exercise challenge altered plasma estrogens but had little effect on CE; estimation of the formation and activity of CE suggests that formation and O-methylation of CE proportionately increases. These findings may be of importance for NE-mediated effects on gonadotropin release.

Plasma 2-hydroxycatecholestrogen responses to acute submaximal and maximal exercise in untrained women.

Exercise-induced menstrual problems are accompanied by an increase in catecholestrogen (CE) formation. It has been hypothesized that hypoestrogenemia may be secondary to an increased turnover from estrogens to CE, which then may disrupt luteinizing hormone release. In addition, the strong affinity of CE for the catecholamine-deactivating enzyme catechol-O-methyltransferase (COMT) has led to speculations about their possible role in safeguarding norepinephrine from premature decomposition during exercise. We investigated whether acute exercise on a cycle ergometer produces any changes in CE homeostasis. Nine untrained eumenorrheic women (body fat, 24.8 +/- 3.1%) volunteered for this study. Baseline plasma CE averages for total 2-hydroxyestrogens (2-OHE) were 218 +/- 29 (SE) pg/ml during the follicular phase (FPh) and 420 +/- 58 pg/ml during the luteal phase (LPh). 2-Methoxyestrogens (2-MeOE) measured 257 +/- 17 pg/ml in the FPh and 339 +/- 39 pg/ml in the LPh. During incremental exercise, total estrogens (E) increased, but 2-OHE and 2-MeOE levels did not significantly change in either phase. The 2-OHE/E ratio (measure of CE turnover) decreased during exercise in both menstrual phases, whereas the 2-MeOE/2-OHE ratio (correlates with COMT activity) did not significantly change. These findings suggest that there is insufficient evidence to conclude that brief incremental exercise in untrained eumenorrheic females acutely produces increased CE formation.

Effects of a training program on resting plasma 2-hydroxycatecholestrogen levels in eumenorrheic women.

Catecholestrogens (CE) represent a major metabolic pathway in estrogen metabolism. Previous information on CE and training is limited to two cross-sectional studies that did not involve standardized training. Our purpose, by means of a prospective design, was to evaluate the effects of a brief, exhaustive training program on resting plasma concentrations of 2-hydroxy CE. The experimental design spanned two menstrual cycles; a control cycle and a training cycle. The subjects were nine previously untrained, eumenorrheic women [body fat: 24.8 +/- 1.0 (SE) %]. Data were collected during the follicular (FPh) and the luteal phases (LPh). Posttraining FPh and LPh tests were held the day after the last day of a 5-day period of training on a cycle ergometer. Total 2-hydroxyestrogens (2-OHE) averaged 200 +/- 29 pg/ml during the FPh and 420 +/- 54 pg/ml during the LPh (P < 0.05). Levels of total 2-methoxyestrogens (2-MeOE) were 237 +/- 32 pg/ml during the FPh and 339 +/- 26 pg/ml during the LPh (P < 0.05). After training, although the plasma levels of 2-OHE significantly decreased (21%; P < 0.05) during the LPh, the actual CE formation (as estimated from the 2-OHE-to-total estrogens ratio) increased (+ 29%; P < 0.05). CE activity, as expressed by the 2-MeOE-to-2-OHE ratio, showed significantly higher values in both phases (FPh, + 14%; LPh, + 13%; P < 0.05). At the same time, resting levels of norepinephrine (NE) were increased by 42% (P < 0.05). CE strongly inhibit biological decomposition of NE by catechol-O-methyltransferase (COMT). Results of the present study suggest that, in response to training, CE are increasingly competing with the enzyme COMT, thus preventing premature NE deactivation.