Pregnancy and the risk of torsades de pointes in congenital long-QT syndrome.

Patients with congenital long-QT syndrome (LQTS) are at increased risk of ventricular arrhythmias during stressful situations. Large-scale studies have pointed out that affected individuals are particularly at risk in the period following pregnancy (post-partum). This is recognised especially for women with an LQTS type 2. Here, we describe two cases of young women with LQTS type 2, both admitted to our institution with symptomatic torsades de pointes a few weeks after delivery. Both patients carried a mutation in the KCNH2 gene. One patient was nullipara, while the other had had an uneventful previous pregnancy. In both cases treatment with a beta-blocker did not prevent life-threatening cardiac arrhythmias. The risk of arrhythmias is thought to gradually decrease to pre-pregnancy values in the nine months after delivery. Considering the difficulties related to continuous monitoring of a patient for such a long period and the desire of these patients to have more children in the foreseeable future, ICD implantation was performed. (Neth Heart J 2008;16:422-5.).

Moraxella catarrhalis sepsis in a patient with juvenile spinal muscle atrophy.

Moraxella catarrhalis rarely causes severe infections or bacteraemia in healthy subjects. In the literature only four cases of clinical sepsis with M. catarrhalis have been described, mostly in immunocompromised patients. We describe a case of a 34-year-old patient with Kugelberg-Welander disease and low body weight (28 kg) who developed clinical sepsis due to M. catarrhalis bacteraemia. A review of the literature is given.

Parity and carotid artery atherosclerosis in elderly women: The Rotterdam Study.

BACKGROUND AND PURPOSE: It has been postulated that physiological changes in the cardiovascular system, lipids, and glucose metabolism during pregnancy may increase subsequent risk of cardiovascular disease. Examination of the association between parity and risk factors for atherosclerosis may contribute information regarding possible mechanisms. METHODS: The relationship of parity with cardiovascular risk factors and the presence of carotid atherosclerosis was examined in the Rotterdam Study, a population-based study comprising 4878 women aged 55 years and older. Carotid atherosclerosis was assessed by ultrasonographic detection of plaques in the common carotid artery and bifurcation. Logistic regression models were used to compute odds ratios and 95% confidence intervals, adjusted for confounding factors. RESULTS: Parity was inversely associated with high-density lipoprotein cholesterol, and alcohol intake. Parity was positively associated with body mass index, total/HDL cholesterol ratio, insulin resistance, age at menopause, and socioeconomic status. Relative to nulliparous women, parous women had 36% (9% to 71%) greater risk of carotid atherosclerosis, rising to 64% in women with >/=4 children (19% to 127%). Adjustment for known cardiovascular risk factors, including insulin resistance and current lipid levels, did not diminish the magnitude of this association. CONCLUSIONS: Data demonstrated that there is a positive association between parity and risk of carotid artery plaques in elderly women and, further, that high parity is associated with lower HDL cholesterol levels and higher glucose/insulin ratios long after childbearing has ceased.

Is open-angle glaucoma associated with early menopause? The Rotterdam Study.

The authors examined the association between age at menopause and open-angle glaucoma among women aged > or = 55 years in the population-based Rotterdam Study (1990--1993). Information on age and type of menopause was obtained by interview. Subjects (n = 3,078) were stratified into three categories according to age at menopause: <45 years, 45--49 years, and > or = 50 years, with the last group serving as the reference group. Diagnosis of open-angle glaucoma was based on the presence of a glaucomatous visual field defect and glaucomatous optic neuropathy. Open-angle glaucoma was diagnosed in 78 women with a natural menopause and 15 women with an artificial menopause. In the category of natural menopause, women who went through menopause before reaching the age of 45 years had a higher risk of open-angle glaucoma than the reference group (odds ratio = 2.6; 95% confidence interval: 1.5, 4.8), after adjustment for age and use of hormone replacement therapy. Among women who went through menopause between the ages of 45 and 49 years, the odds ratio was 1.1 (95% confidence interval: 0.7, 2.0). These findings suggest that early menopause is associated with a higher risk of open-angle glaucoma.

Direct coronary stent implantation: safety, feasibility, and predictors of success of the strategy of direct coronary stent implantation.

This prospective study was designed to evaluate the feasibility, safety, predictive factors of success, and 6-month follow-up of stent implantation without balloon predilatation (direct stenting) in 250 patients undergoing elective stent implantation. Balloon dilatation prior to stent implantation was a prerequisite to facilitate passage and deployment of the stent. Stent technology has changed tremendously, resulting in stents with improved properties, which may allow stent placement without prior balloon dilatation. Patients with coronary lesions suitable for elective stent implantation were included in this trial. Coronary interventions were undertaken predominantly via the transradial route using 6 Fr guiding catheters. Direct stent implantation was attempted using AVE GFX II coronary stent delivery systems. Upon failure, predilatation was undertaken before reattempting stent implantation. Patient data and ECGs were obtained from case records and from personal or telephone interviews 6 months after the procedure. Values were presented as mean +/- standard deviation. Student's t-test, two-tailed at 5% level of significance, was used to compare the difference of two means. Multivariate logistic regression analysis was performed to establish predictive factors for failure of direct stenting. Two hundred and sixty-six direct stent implantations were attempted in 250 patients. Direct stenting was successful in 226 (85%) cases. Out of 40(15%) cases where direct stenting failed, balloon predilatation facilitated stent implantation in 39. In one lesion, stent implantation was not possible despite adequate predilatation. Predictive factors for failure of direct stenting on multivariate analysis were LCx lesions (P < 0.01), complex lesions (P < 0.01), and longer stents (P < 0.001). Minimal luminal diameter and percentage diameter stenosis of lesions in the successful and the failure group were not significantly different (0.94 +/- 0.39 mm vs. 0.84 +/- 0.41 mm, P = NS, and 70.2 +/- 11.2 vs. 73.2 +/- 11.2, P = NS). Stent loss occurred in five (2.0%) cases, with successful retrieval in four. One stent was lost permanently in a small branch of the radial artery. Post-percutaneous coronary intervention (post-PCI) myocardial infarction occurred in four (1.6%) patients. There were no other in-hospital events. Six-month-follow up information was obtained in 99% of patients. Subacute stent thrombosis was noted in four (1.6%) cases. Target vessel-related myocardial infarction rate was 3.2%, of which half was caused by subacute stent thrombosis. The overall reintervention rate (coronary artery bypass grafting or PCI) was 9.7%. Target lesion revascularization by PCI occurred in only 4.0%. At 6 months, overall mortality was 2.0%, of which 1.2% was due to coronary events. Direct stent implantation is safe and feasible in the majority of cases with low rate of complications. Unfavorable factors include circumflex lesion, more complex lesion morphology, and increasing length of stent. Severity of stenosis does not appear to be of predictive value. Long-term outcome is favorable with a low target lesion revascularization rate.

Oestrogen, atherosclerosis and cardiovascular disease in women: Epidemiological studies on menopause and hormone replacement therapy.

What part menopause and hormone replacement therapy (HRT) play in the risk of cardiovascular disease in women after middle-age is still debated. The associations between menopause, HRT and cardiovascular disease as well as atherosclerosis were examined in a large cohort study. Our results suggest menopause has an unfavorable association with several cardiovascular risk factors, structural characteristics of the large arteries, on atherosclerosis and on coronary heart disease. HRT was shown to protect women from development of atherosclerosis in the lower extremities and in the common carotid artery. This suggests that the mechanisms underlying this protection include inhibition of the atherosclerotic process. Our analyses of a randomised, placebo-controlled study could not confirm the effect on HRT on atherosclerosis of the common carotid artery. As findings from large randomised trials do not confirm the benefit of estrogen therapy for prevention of cardiovascular disease no definite conclusions can be drawn, and HRT should not be recommended for this purpose in clinical practice.

The effect of hormone replacement therapy on arterial distensibility and compliance in perimenopausal women: a 2-year randomised trial.

A single centre randomised placebo-controlled trial was performed to assess the 2-year effects of hormone replacement therapy compared to placebo on mechanical arterial properties in 99 perimenopausal women recruited from the general population. The trial was double-blind with respect to a sequential combined regimen of oral 17beta-oestradiol and desogestrel (17betaE(2)-D) and the placebo group and open with respect to combination of conjugated equine oestrogens and norgestrel (CEE-N). At baseline, distensibility and compliance of the common carotid artery were measured non-invasively with B-mode ultrasound and a vessel wall movement detector system, and the distensibility coefficient (DC) and compliance coefficient (CC) were calculated. Measurements were repeated after 6 and 24 months. Change in DC and CC in treatment groups was compared to placebo. After 24 months, changes for 17betaE(2)-D compared to placebo were -1.4x10(-3)/kPa (95% CI -4.4; 1.7, P=0.39) for DC and 0. 26 mm(2)/kPa (95% CI -0.01; 0.53, P=0.07) for CC. Changes for CEE-N compared to placebo were 0.4x10(-3)/kPa (95% CI -1.0; 1.9, P=0.79) and 0.11 mm(2)/kPa (95% CI -0.14; 0.37, P=0.40). For systolic blood pressure (SBP), diastolic blood pressure (DBP) and arterial lumen diameter no changes were found. In this study no significant differences in changes in distensibility and compliance were found between perimenopausal women using 17betaE(2)-D or CEE-N and women using placebo after 6 and 24 months.

Hormone replacement therapy and peripheral arterial disease: the Rotterdam study.

BACKGROUND: As the number of elderly women increases in Western society, peripheral arterial disease (PAD) is likely to become an increasing problem. Hormone replacement therapy, suggested to protect against coronary atherosclerosis, might also inhibit the development of PAD. METHODS: The association between hormone replacement therapy and the presence of PAD was studied in a population-based study consisting of 2196 naturally menopausal women aged 55 to 80 years living in a suburban area of Rotterdam, the Netherlands. Peripheral arterial disease was defined as an ankle/arm systolic blood pressure index (ratio of the systolic blood pressure at the ankle to the systolic blood pressure at the arm) lower than 0.9. RESULTS: Hormone replacement therapy for 1 year or longer was associated with a 52% decreased risk of PAD (odds ratio, 0.48 [95% confidence interval, 0.24-0.85]), while no association was found for therapy duration shorter than 1 year (odds ratio, 0.97 [95% confidence interval, 0.58-1.63) after adjustment for age, smoking, and socioeconomic status. Additional adjustment for body mass index, age at menopause, total cholesterol and high-density lipoprotein cholesterol, alcohol intake, and frequency of visits to health care facilities did not change the results. CONCLUSION: The findings of this population-based study suggest that hormone replacement therapy given for a year or more is associated with a decreased risk of PAD among postmenopausal women.

Variables of the insulin resistance syndrome are associated with reduced arterial distensibility in healthy non-diabetic middle-aged women.

AIMS/HYPOTHESIS: The insulin resistance syndrome is related to arterial stiffness in diabetic subjects. Whether the insulin resistance syndrome is also related to arterial stiffness in non-diabetic subjects is less clear. We studied the association between variables of the insulin resistance syndrome in relation to arterial distensibility in healthy middle-aged non-diabetic women. METHODS: This study was done in 180 non-diabetic women, aged 43-55, selected from the general population. Arterial distensibility was assessed in the carotid artery. The associations were evaluated using linear regression analyses. RESULTS: Strong associations were found between arterial distensibility and the variables of the insulin resistance syndrome: body mass index, waist-to-hip ratio, high-density-lipoprotein-cholesterol, triglycerides, glucose, insulin, apolipoprotein A1, plasminogen activator inhibitor-1-antigen and tissue-type plasminogen activator-antigen. After additional adjustment for mean arterial pressure, common carotid arterial distensibility remained associated with body mass index: beta-coefficient (95% confidence interval) per kg/m2: -0.24 (-0.42; -0.06); waist-to-hip ratio: -26.62 (-40.59; -12.65) per m/m; triglycerides: -1.42(-2.77; -0.08) per mmol/l; plasminogen activator inhibitor-1-antigen: -0.01 (-0.02; -0.00) per ng/ml and borderline significant associated with high-density-lipoprotein-cholesterol: 1.93 (-0.01; 3.87; p = 0.07) per mmol/l. Clustering of variables of the insulin resistance syndrome was strongly related to decreased arterial distensibility which remained after adjustment for mean arterial pressure. No association was found between arterial distensibility and variables that are not part of the insulin resistance syndrome: total cholesterol, LDL-cholesterol and apolipoprotein B. CONCLUSION/INTERPRETATION: The results of this study show that variables of the insulin resistance syndrome are associated with decreased arterial distensibility of the common carotid artery in healthy non-diabetic subjects.

Increased plasma homocysteine after menopause.

Besides genetic defects in the enzymes involved in homocysteine metabolism and nutritional deficiencies in vitamin cofactors, sex steroid hormones may modulate plasma homocysteine levels. The post-menopausal state has been found to be associated with higher plasma homocysteine levels, but data are inconsistent and studies published so far did not adjust for age, which is an important confounding factor in studying the effect of menopause. In the present study total plasma homocysteine levels were measured in a meticulously selected population in which the contrast in estrogen status between pre- and postmenopausal women of the same age was maximized. The study comprised 93 premenopausal and 93 postmenopausal women of similar age (range 43-55 years). Women were selected from respondents to a mailed questionnaire on menopause, which was sent to all women aged 40-60 years in the Dutch town of Zoetermeer (n = 12675). Postmenopausal women who were at least three years after menopause or whose menses had stopped naturally before age 48 were age-matched with premenopausal women with regular menses and without menopausal complaints. Plasma homocysteine levels in the fasting state were related to menopausal status; the age-adjusted geometric mean was 10.7 micromol/l in premenopausal and 11.5 micromol/l in postmenopausal women (difference of 7%, 95% confidence interval 0.3-14%, P = 0.04). Additional adjustment for plasma creatinine, body mass index, smoking habit (yes, no) and alcohol intake did not influence this difference. The results of this population-based study indicate that plasma homocysteine is affected by menopause.

Hormone replacement therapy and intima-media thickness of the common carotid artery: the Rotterdam study.

BACKGROUND AND PURPOSE: Observational data suggest that hormone replacement therapy (HRT) reduces morbidity and mortality from cardiovascular disease in healthy postmenopausal women. The mechanisms underlying this protection are not entirely clear but may include inhibition of the atherosclerotic process. METHODS: We studied the association between ever use of HRT and intima-media thickness (IMT) of the common carotid artery in 1103 naturally menopausal women, aged 55 to 80 years, in the Rotterdam Study, a community-based cohort study in a suburban area of Rotterdam, Netherlands. Mean and maximum IMT of the common carotid artery were measured noninvasively with B-mode ultrasound. RESULTS: Ever use of HRT for >/=1 year was associated with a decreased mean and maximum IMT compared with never users (mean IMT, 0.719 mm [SE 0.01] versus 0. 742 mm [SE 0.004], P=0.03; maximum IMT, 0.952 mm [SE 0.015] versus 0. 983 mm [SE 0.006], P=0.04), after adjustment for age, smoking, educational level, systolic blood pressure, and body mass index. No association was found for use <1 year (mean IMT, 0.739 mm [SE 0.013] versus 0.742 mm [SE 0.004], P=0.69; maximum IMT, 0.990 mm [SE 0.019] versus 0.983 mm [SE 0.006], P=0.75). Additional adjustment for diabetes, frequency of visits to healthcare facilities, or total and HDL cholesterol did not change these results. CONCLUSIONS: The findings of this population-based study show that ever use of HRT is associated with a decreased IMT in the common carotid artery in elderly women.

Hormone replacement therapy in perimenopausal women and 2-year change of carotid intima-media thickness.

OBJECTIVES: To assess the 2-year effects of a combined regimen of oral 17beta-estradiol and desogestrel (17betaE-D) and a sequential combination of conjugated equine estrogens and norgestrel (CEE-N) on common carotid intima-media thickness and end-diastolic lumen diameter in comparison to placebo in perimenopausal women. METHODS: The study was a single center, randomized, group-comparative, double-blind study with respect to the 17betaE-D and placebo groups and open with respect to CEE-N. After cycle 6, the blind was broken and the trial was continued as an open trial for another 18 months for the active study arms. The study included 121 perimenopausal women recruited from the general population. Common carotid intima-media thickness and end-diastolic lumen diameter were measured at baseline and cycle 24 with B-mode ultrasonography. RESULTS: At cycle 24 small changes in intima-media thickness and lumen diameter were observed. Relative to placebo, changes in intima-media thickness were -0.009 mm [95% CI -0.045; 0.027] for 17betaE-D and -0.016 mm [95% CI -0.055; 0.024] for CEE-N. For end-diastolic lumen diameter the changes were -0.091 mm [95% CI -0.236; 0.055] and -0.125 mm [95% CI -0.820; 0.032] for 17betaE-D and CEE-N, respectively. CONCLUSIONS: In this study among perimenopausal women a significant effect of 17betaE-D and CEE-N on common carotid intima-media thickness and lumen diameter could not be demonstrated. Although the sample size of the present trial is too limited to provide definite conclusions, the direction of the effect is in agreement with evidence from earlier studies on the effects of hormone replacement therapy in postmenopausal women.

Estrogen receptor polymorphism predicts the onset of natural and surgical menopause.

Age at menopause and risk of hysterectomy have strong genetic components, but the genes involved remain ill defined. We investigated whether genetic variation at the estrogen receptor (ER) gene contributes to the variability in the onset of menopause in 900 postmenopausal women, aged 55-80 yr, of the Rotterdam Study, a population-based cohort study in The Netherlands. Gynecological information was obtained, and if women reported surgical menopause, validation of type and indication of surgery was accomplished by checking medical records. The ER genotypes (PP, Pp, and pp) were assessed by PCR using the PvuII endonuclease. Compared with women carrying the pp genotype, homozygous PP women had a 1.1-yr (P < 0.02) earlier onset of menopause. Furthermore, an allele dose effect was observed, corresponding to a 0.5-yr (P < 0.02) earlier onset of menopause per copy of the P allele. The risk of surgical menopause was 2.4 (95% confidence interval, 1.5-3.8) times higher for women carrying the PP genotype compared to those in the pp group, with the most prominent effect in women who underwent hysterectomy due to fibroids or menorrhagia. We conclude that genetic variations of the ER gene are related to the onset of natural menopause and the risk of surgical menopause, especially hysterectomy.

Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women.

Obesity, the insulin resistance syndrome, and atherosclerosis are closely linked and may all be determinants of an increased acute-phase response. In this study, we examined the relationship of C-reactive protein (CRP) with measures of obesity, variables of the insulin resistance syndrome, and intima-media thickness of the common carotid arteries in 186 healthy, middle-aged women selected from the general population. Associations were assessed by regression analysis. CRP was strongly associated with body mass index (BMI) and waist circumference. CRP was also associated with other variables of the insulin resistance syndrome, including blood pressure, insulin, high density lipoprotein cholesterol, triglycerides, apolipoprotein A1 (inversely), plasminogen activator inhibitor-1 antigen, and tissue-type plasminogen activator antigen. Associations between CRP and the variables of the insulin resistance syndrome disappeared after controlling for BMI but remained significant for plasminogen activator inhibitor-1 antigen only. The association of CRP with common carotid artery intima-media thickness was weak and limited to ever-smokers. BMI explained 29.7% of the variance of CRP, whereas common carotid artery intima-media thickness explained only 3.7%. The results of this population-based study indicate that adiposity is strongly associated with CRP in healthy, middle-aged women. In this population, BMI accounted for the relationship between CRP and other variables of the insulin resistance syndrome. Further studies should determine whether losing weight ameliorates the inflammatory state.

Menopausal status and distensibility of the common carotid artery.

Although several studies have shown that exogenous estrogens have beneficial effects on arterial characteristics, the effect of endogenous estrogen on the vascular system is still unknown. In this study, distensibility, an indicator of arterial elasticity, of the common carotid artery was compared in pre- and postmenopausal women. The study comprised 93 premenopausal and 93 postmenopausal women of similar age (range, 43 to 55 years). Women were selected from respondents to a mailed questionnaire about the menopause, which was sent to all women aged 40 to 60 years in the Dutch town of Zoetermeer (n=12 675). Postmenopausal women who were at least 3 years past natural menopause or whose menses had stopped naturally before age 48, were age-matched with premenopausal women with regular menses and without menopausal complaints. The selection aimed at maximizing the contrast in estrogen status between pre- and postmenopausal women of the same age. Distensibility of the carotid artery was measured noninvasively with B-mode ultrasound and a vessel wall movement detector system. Arterial distensibility is expressed as the change in arterial diameter (distension, DeltaD) with the cardiac cycle, adjusted for lumen diameter, pulse pressure, and mean arterial blood pressure. Compared with premenopausal women, postmenopausal women had significantly lower arterial distension (DeltaD 370.5 microm [SE 9.5] versus 397.3 microm [SE 9.6]). These results suggest that the distensibility of the common carotid artery is negatively affected by natural menopause in presumed healthy women.

Menopausal status and risk factors for cardiovascular disease.

OBJECTIVES: Changes in cardiovascular risk factors with menopausal status are difficult to study, owing to the high correlation of menopausal status with age. Therefore we examined cardiovascular risk factors in a meticulously selected population in which the contrast in oestrogen status between pre- and postmenopausal women of the same age was maximized. DESIGN: Risk factors were compared in 93 premenopausal and 93 postmenopausal women who were matched on age (range 43-55 years). SETTING: The women were selected from respondents to a mailed questionnaire about the menopause, which was sent to all women aged 40-60 years in the Dutch town of Zoetermeer (n = 12 675; response 54%). SUBJECTS: Postmenopausal women who were at least 3 years after menopause or whose menses had stopped naturally before age 48 were age-matched with premenopausal women with regular menses and without menopausal complaints. RESULTS: Compared to premenopausal women, postmenopausal women had significantly increased levels of total cholesterol (10.0%, 95% confidence interval 5.1-14.0), low density lipoprotein (LDL) cholesterol (14.0%, 6.9-19.9), and apolipoprotein B (8.2%, 0.6-15.5). The difference was present within 3 years after onset of menopause and did not show a trend towards an increase with the number of postmenopausal years. No differences were found in high density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1, blood glucose, insulin, body mass index, waist-to-hip ratio, and systolic and diastolic blood pressure. CONCLUSIONS: The results of this study add to the evidence that total cholesterol, LDL cholesterol and apolipoprotein B are the primary cardiovascular risk factors affected by menopause.

Prevalence of Asherman's syndrome after secondary removal of placental remnants or a repeat curettage for incomplete abortion.

This prospective study assesses the prevalence of intrauterine adhesions among women undergoing secondary removal of placental remnants after delivery, or a repeat curettage for incomplete abortions, and evaluates risk factors associated with the presence of intrauterine adhesions. In 50 women, undergoing either a secondary removal of placental remnants more than 24 h after delivery, or a repeat curettage for incomplete abortions, ambulatory hysteroscopy was performed 3 months after the intervention. Intrauterine adhesions were found in 20 of the women (40%): five patients had Asherman's syndrome grade I, six had grade II, six had grade III and three had grade IV. In women with menstrual disorders a statistically significant 12-fold increased risk for Asherman's syndrome grade II-IV was found. Previous abortion as well as infection during surgery were associated with a mildly but non-significant increased risk. Based on our findings, hysteroscopy is recommended only in those patients who develop menstrual disorders, either after secondary intervention for placental remnants after delivery or after a repeat curettage.