High-risk lesions in high-risk women: a high-risk formalin-based biology!
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Breast Neoplasms↗
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Worry about ovarian cancer risk and use of screening by high-risk women: how you recruit affects what you find.
Several studies have described the characteristics of women at high-risk for ovarian cancer who are participating in registry studies and high-risk screening programs. These studies have found high-risk women to report high levels of perceived risk and worry about their risk for ovarian cancer. In contrast, population based studies have found that while high-risk women did report high levels of perceived risk, they did not report high levels of worry about their risk. In this study, we examine reports of perceived risk, worry about ovarian cancer, and use of screening by high-risk women recruited to participate in a survey from several recruitment sources. These sources include self-, physician-, and affected patient relative-referral, a fundraising mailer, and a mass mailing to a commercial mailing list. High-risk women recruited via mass mailing were less likely than those recruited via physicians or affected relatives to report either worry about their risk or use of ovarian cancer screening tests.
Adult↗
Patient preference for counselling predicts postpartum depression: a prospective 1-year follow up study in high-risk women.
BACKGROUND: Patient preferences have been associated with a positive effect of depression treatment. Little is known about patient preferences in at-risk samples. The aim of this study was to examine the role of patient preference for counselling in the occurrence of postpartum depression in high-risk women. METHOD: We conducted a prospective 1-year follow up study in two hospitals and four midwifery practices in The Netherlands. Participants were 90 pregnant women at high risk for postpartum depression: 45 high-risk women who preferred no counselling, 45 high-risk women who preferred counselling. Both groups received care as usual. The main outcome measure was clinical depression (Research Diagnostic Criteria) at 3, 6, and 12 months postpartum. RESULTS: Point-prevalence rates of clinical depression were significantly higher in high-risk women who preferred counselling compared with high-risk women who did not prefer counselling (24% versus 9%, P=0.048; 19% versus 5%, P=0.048, at 3 and 6 months postpartum, respectively). No significant difference was found at 12 months postpartum. Across the first-year postpartum, high-risk women who preferred counselling were at seven-fold increased risk for clinical depression (OR=7.7, 95% CI 1.7-33.8, P=0.007). CONCLUSIONS: Patient preference for counselling is an important predictor of postpartum depression in pregnant women at high risk for postpartum depression. Patient preferences may reflect validly a perceived need for intervention in high-risk women. This finding emphasises the need to take patient preference for counselling into account as an important variable to identify a high-risk population.
Adult↗
Pre- and postmenopausal high-risk women undergoing screening for ovarian cancer: anxiety, risk perceptions, and quality of life.
OBJECTIVE: Recommendations for women at high risk of ovarian cancer include prophylactic salpingo-oophorectomy (PSO) or screening with transvaginal ultrasonography (TVUS) and CA125 levels. The best strategy for improving survival and maintaining quality of life in high-risk women is not known. Premenopausal women may be more reluctant than postmenopausal women to undergo PSO. However, the risk of false-positive screening results may be more likely in premenopausal women, posing potential psychological risk for those enrolled in high-risk ovarian cancer surveillance programs. We sought to determine whether anxiety, depression, perception of ovarian cancer risk, and false-positive test frequency differed between high-risk premenopausal and postmenopausal women initiating ovarian cancer screening. METHODS: High-risk women aged > or = 30 years enrolling in a TVUS plus CA125 ovarian cancer screening study completed standard QOL (SF-36), cancer-specific anxiety (IES), depression (CES-D), and ovarian cancer risk perception measures. CA125 > 35 and TVUS showing solid or complex cystic ovarian masses were considered abnormal. Abnormal tests were repeated after 4-6 weeks. Persistently abnormal tests prompted a search for malignancy. Tests that normalized on repeat were considered false positive. RESULTS: One hundred forty-seven high-risk women, median age 46 (range, 30-78), 78 premenopausal and 69 postmenopausal, had > or = 1 TVUS/CA125/outcome assessment. Premenopausal women were more likely than postmenopausal women to consider themselves at higher risk of ovarian cancer compared with women their age (P < 0.001) and compared with women with similar family histories (P < 0.001). Mean personal perception of lifetime risk of ovarian cancer among premenopausal women was 37% (range, 0-90%) versus 26% (range, 0-60%) among postmenopausal women (P = 0.02). While general QOL and depression scores were similar, 38% of premenopausal women reported high anxiety versus 27% of postmenopausal women (P = 0.03). Thirty percent of women required repeat CA125 or TVUS after first screening; 10.8% of premenopausal women versus 4.6% of postmenopausal women required repeat CA125; and 23.3% of premenopausal and 20.6% of postmenopausal women required repeat TVUS. One postmenopausal woman with persistently rising CA125 >100 had negative mammography, colonoscopy, and dilation and curettage/bilateral salpingo-oophorectomy. All other abnormal tests normalized on repeat. Two premenopausal women withdrew due to anxiety following false-positive CA125 results. Five women (2 premenopausal, 3 postmenopausal) with normal TVUS/CA125 screening tests elected PSO, with benign findings. CONCLUSION: Premenopausal women perceive their ovarian cancer risk to be higher, report greater ovarian cancer risk-related anxiety, and are more likely to have false-positive screening results than postmenopausal women. Few high-risk women elect PSO in the short term. Knowledge of the frequency of false-positive screening results and psychosocial outcomes is important for high-risk women choosing strategies for managing ovarian cancer risk.
Adult↗
Impact of screening for breast cancer in high-risk women on health-related quality of life.
The effectiveness of intensive surveillance in women at high risk for breast cancer due to a familial or genetic predisposition is uncertain and is currently being evaluated in a Dutch magnetic resonance imaging (MRI) screening (MRISC) study, in which annual imaging consists of mammography and MRI. Unfavourable side effects on health-related quality of life may arise from this screening process. We examined the short-term effects of screening for breast cancer in high-risk women on generic health-related quality of life and distress. A total of 519 participants in the MRISC study were asked to complete generic health-status questionnaires (SF-36, EQ-5D) as well as additional questionnaires for distress and items relating to breast cancer screening, at three different time points around screening. The study population showed significantly better generic health-related quality of life scores compared to age-/sex-adjusted reference scores from the general population. Neither generic health-related quality of life scores nor distress scores among the study sample (n=334) showed significant changes over time. The impact of the screening process on generic health status did not differ between risk categories. Relatively more women reported mammography as quite to very painful (30.1%) compared to MRI. Anxiety was experienced by 37% of the women undergoing MRI. We conclude that screening for breast cancer in high-risk women does not have an unfavourable impact on short-term generic health-related quality of life and general distress. In this study, high-risk women who opted for regular breast cancer screening had a better health status than women from the general population.
Adult↗
What high-risk women are telling us about access to primary and reproductive health care and HIV prevention services.
Focus group discussions on barriers to health care and attitudes toward family planning, reproductive health services, and condom use were conducted with 63 women at high risk for HIV due to their own injection drug use, sex with injection drug users, sex industry work, or a history of multiple sexually transmitted diseases. Barriers identified include the high cost of health care, perceived poor quality of care and experiences of discrimination and stigmatization, geographic accessibility, fear of legal/social services punitive actions, misperceptions about the efficacy of birth control methods and condom usage, lack of sterilization services, and lack of male involvement. Where possible, findings from the focus groups are supported with quantitative survey data from a sample of high-risk women (n = 723). Recommendations are made for improving care for high-risk women.
Adult↗
Additional salpingectomy after previous prophylactic oophorectomy in high-risk women: sense or nonsense?
OBJECTIVES: Since BRCA1/2 germ line mutation carriers are also at a higher risk of developing fallopian tube carcinoma, resection of the fallopian tubes is currently included at the time of risk reducing surgery. In this study, we comment on the need of additional bilateral prophylactic salpingectomy (BPS) following previous bilateral prophylactic oophorectomy (BPO) in women at high risk of ovarian cancer. METHODS: Retrospectively, the medical files of 42 high-risk women, who had undergone BPO only, were reviewed. RESULTS: In our center, risk-reducing surgery consisted of BPO only for 42 women. Twenty-seven women received an informative letter in which counseling for additional BPS was offered. In total, 15 women opted for additional BPS. Surgery was performed with a mean interval of 65 months (range 6-101) in 10 BRCA1 carriers, one BRCA2 carrier, one BRCA1 and 2 carrier, and three women with non-informative test results. The procedure was readily done by laparoscopy in 13 women and two needed a laparotomy. No post-operative complications had occurred. Histopathological examination revealed no malignancy. CONCLUSIONS: We believe that additional risk reduction of cancer necessitates BPS in BRCA1/2 carriers after previous BPO. BPS after previous BPO was easily performed. Today, physicians should include resection of the fallopian tube at prophylactic surgery in high-risk women and should consider additional BPS in women who have undergone BPO only.
Adult↗
Home births for high risk women result in high death rates
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Journal Article↗
A specific RAD51 haplotype increases breast cancer risk in Jewish non-Ashkenazi high-risk women.
While the precise genes involved in determining familial breast cancer risk in addition to BRCA1/2 are mostly unknown, one strong candidate is RAD51. Jewish non-Ashkenazi women at high-risk for breast/ovarian cancer and ethnically matched controls were genotyped using four single nucleotide polymorphisms spanning the RAD51 genomic region, and the resulting haplotypes were constructed using the GERBIL algorithm. A total of 314 individuals were genotyped: 184 non-Ashkenazi high-risk women (119 with breast cancer), and 130 unaffected, average-risk ethnically matched controls. Using GEBRIL, three frequent haplotypes were constructed. One of the haplotypes (TGTA - coined haplotype 3) was present in 7.3% (19/260 haplotypes) of controls (n=130) and in 16.8% (40/238 haplotypes) of high-risk breast cancer patients (n=119, P=0.001). A specific RAD51 haplotype is more prevalent among non-Ashkenazi Jewish high-risk women than in average-risk population.
Breast Neoplasms↗
Osteoporosis: what are the implications of DEXA scanning 'high risk' women in primary care?
BACKGROUND: Current recommended practice for the use of dual X-ray absorptiometry (DEXA) scans in screening for osteoporosis is to concentrate on women at 'high risk'. OBJECTIVE: We have applied such a screening strategy, in a general practice setting, to estimate the number of women requiring scans. METHODS: A two-phase survey was carried out: (i). postal screen of clinical indicators for low bone mineral density (BMD) to define women at 'high risk'; and (ii). DEXA scanning of the sample at 'high risk' set in two general practices in North Staffordshire. Computerized general practice records were used to define a purposive sample of 1001 women, to receive the screening tool, consisting of three equal size groups (i). those with an early hysterectomy; (ii). those receiving oral corticosteroids on repeat prescription; and (iii). those on the practice cervical smear register. A random sample of women defined at 'high risk' by the screening tool were invited to have a DEXA scan. The main outcome of interest was the presence of low BMD as measured by a DEXA scanner. RESULTS: Sixty-five out of 95 women invited (68%) agreed to undergo a DEXA scan: median age = 52 years (interquartile range 44-64 years). Twenty-nine of these 65 women (45%) were classified with low BMD (WHO criteria): 90% had densities below their age-matched mean. Extrapolating from the observed findings to the main study practice (n = 9000 total population), we estimate that 162 women would be defined at 'high risk', and, if all were offered a scan, 105 would comply and 56 would be defined with low BMD. CONCLUSIONS: Using this approach, we estimate the unmet need, in women, for DEXA scans to be 180 per 10000 total practice population. Allowing for scan uptake, this would define approximately 60 women per 10000 total practice population with low BMD. The application of this screening strategy has identified a group of women who might benefit from treatment or prophylaxis for osteoporosis.
Absorptiometry, Photon↗
Methylation profiles of sporadic ovarian tumors and nonmalignant ovaries from high-risk women.
PURPOSE: The purpose of this research was to examine the DNA methylation profiles of primary sporadic ovarian cancers and ovarian tissues from high-risk women. EXPERIMENTAL DESIGN: We analyzed the DNA methylation status of nine cancer-related genes in 49 primary ovarian tumors, 39 nonmalignant ovarian tissues obtained from 16 women with no known risk and from 23 high-risk women with a strong family history of breast and/or ovarian cancer or BRCA1 germ-line mutations, and 11 ovarian cancer cell lines, by methylation-specific PCR. RESULTS: Our findings are as follows: (a) methylation rates of four of nine genes, RASSF1A (41%), HIC1 (35%), E-cadherin (29%), and APC (18%) were significantly higher in tumors compared with controls. At least one of the four genes was methylated in 76% of the tumors; (b) a low frequency of methylation was present in nonmalignant tissues; (c) no significant differences in methylation frequencies were seen between the nonmalignant ovarian tissues from women at high-risk and those with no known risk of developing ovarian cancer; (d) methylation of the BRCA1 gene was found in 10% of sporadic tumors but in none of the samples from women with a germ-line BRCA1 mutation; and (e) ovarian cancer cell lines showed a similar frequency of methylation to ovarian tumors except for the HIC1 gene. CONCLUSIONS: Our results suggest that aberrant methylation of specific genes, including two not described previously, may be important in ovarian cancer pathogenesis but not in ovaries at risk for cancer development.
DNA↗
Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women.
Tamoxifen improves outcome in women with breast cancer and reduces the incidence of estrogen receptor-positive (ER+) breast tumors in prevention trials. Tamoxifen use is associated with an increased risk of potentially serious adverse events, principally endometrial cancer and venous thromboembolic events and, therefore, detailed knowledge of the effects of tamoxifen is important. With more cases of breast cancer being found as the follow-up time increases, it is now possible to perform more detailed analysis of the Italian Randomized Trial of Tamoxifen. Women with hysterectomy (N = 5408) were randomly assigned to receive 20 mg tamoxifen per day (N = 2700) or placebo (N = 2708). After a median of 81.2 months of follow-up, 79 case subjects (34 in the tamoxifen arm and 45 in the placebo arm) were diagnosed with breast cancer. We were able to identify a group of women at increased risk of ER+ breast cancers (high-risk group) on the basis of baseline as well as reproductive and hormonal characteristics (height, age at menarche, parity, age at first birth, and oophorectomy). Tamoxifen administered to women in the high-risk group showed statistically significantly reduced incidence of breast cancer (tamoxifen, 3 and placebo, 15; P =.003), but no such effect was seen in the low-risk group (tamoxifen, 31 and placebo, 30; P =.89). The positive effect of tamoxifen on breast cancer among high-risk women is most marked for ER+ tumors (tamoxifen, 1 and placebo, 11; P =.002). Chemoprevention of breast cancer with tamoxifen appears to be effective in women at high risk of ER+ tumors but not among women at low risk, who may well be protected naturally by late age at menarche or early first pregnancy, or artificially by removal of the ovaries. Tamoxifen could be offered as a preventive agent to women identified at high-risk of breast cancer because of hormone-related risk factors. Such a strategy would greatly reduce the numbers of women who would need to take tamoxifen to obtain the same absolute reduction in breast cancer. These findings are exploratory and need to be confirmed in other randomized trials.
Antineoplastic Agents, Hormonal↗
Mid-trimester uterine artery Doppler screening as a predictor of adverse pregnancy outcome in high-risk women.
OBJECTIVE: To assess the value of uterine artery Doppler ultrasound screening, when performed in a clinical setting, to predict complications of impaired uteroplacental blood flow in high-risk women. DESIGN: A prospective audit. SUBJECTS: A total of 116 pregnancies in 114 women at high risk of pre-eclampsia and/or small-for-gestational-age (SGA) babies attending a maternal-fetal medicine clinic at National Women's Hospital, a tertiary referral hospital, Auckland, New Zealand. METHODS: Uterine artery Doppler screening was performed as part of clinical practice between 22 and 24 weeks' gestation. A resistance index (RI) was calculated from each uterine artery and the presence or absence of a notch was determined. An RI of > 0.58 was defined as abnormal and an RI of > or = 0.7 was defined as very abnormal. The main outcome measures were: pre-eclampsia, SGA baby (birth weight < 10th centile), placental abruption, intrauterine death, 'all' and 'severe' outcomes. RESULTS: Thirty-two (27.5%) women developed pre-eclampsia, 31 (26.7%) had SGA babies, 23 (20%) were delivered at < 34 weeks because of pregnancy complications, and there were three (2.6%) placental abruptions and three (2.6%) perinatal deaths. The sensitivity of any RI of > 0.58 for pre-eclampsia, SGA, 'all' outcomes and 'severe' outcome was 91%, 84%, 83% and 90%, respectively. The specificity of any RI of > 0.58 for these outcomes was 42%, 39%, 47% and 38%, respectively. The positive predictive value of any RI of > 0.58 for the same outcomes was 37%, 33%, 58% and 24%, respectively. Among women with both RI values of > or = 0.7, 58%, 67%, 85% and 58% developed pre-eclampsia, SGA, 'all' and 'severe' outcomes, respectively. In women with bilateral notches, 47%, 53%, 76% and 65% developed the respective outcomes. Women with both RI values of > or = 0.7 and women with bilateral notches had relative risks of 11.1 (95% CI 2.6-46.4) and 12.7 (95% CI 4.0-40.4) for developing severe outcome, respectively. Only 5% of women with both RI values of < 0.58 developed a severe outcome. CONCLUSION: In high-risk women, uterine artery Doppler waveform analysis performed best in the prediction of severe adverse outcome and was better than clinical risk assessment in the prediction of pre-eclampsia and SGA babies. Further studies are necessary to determine how information from uterine artery Doppler studies should modify current practice in high-risk women.
Adult↗
Quinacrine sterilization (QS) among high-risk women: a study of 134 cases.
OBJECTIVE: To determine if quinacrine sterilization (QS) is safe and effective in women at high risk for surgery. METHODS: A trial was initiated at the Government Medical College in Patiala, India, in December 1993. Patient intake was terminated in July 1999 and the cut-off date for this analysis was March 31, 2003. Using a modified IUD inserter, seven 252 mg quinacrine pellets with 50 mg of diclofenac were transcervically inserted into the uterus. DMPA 150 mg was administered IM at the time of the first insertion as a back-up contraceptive. This same combination was inserted a month later. A total of 134 women underwent QS. Of these, 92 were considered to be at high risk for surgery, 27 were afraid of surgery or voluntarily opted for QS, and 15 had had failed surgical sterilization or surgery was found not to be technically feasible. Follow-up was scheduled for 1, 3, 6 and 12 months, and then annually after the second insertion or whenever side effects or complications were experienced. RESULTS: Mean follow-up was 7.2 years. No pregnancies or serious complications were experienced. CONCLUSION: QS is a safe and effective option for women at high risk of surgical complications.
Adult↗
Prevalence of aneuploidy, overexpressed ER, and overexpressed EGFR in random breast aspirates of women at high and low risk for breast cancer.
Breast tissue biomarkers which accurately predict breast cancer development within a 10 year period in high risk women are needed but currently not available. We initiated this study to determine 1) the prevalence of one or more breast tissue abnormalities in a group of women at high risk for breast cancer, and 2) if the prevalence of biomarker abnormalities is greater in high risk than in low risk women. Eligible high risk women were those with a first degree relative with breast cancer, prior breast cancer, or precancerous mastopathy. Low risk women were those without these or other major identifiable risk factors. Ductal cells were obtained via random fine needle aspirations and cytologically classified. Biomarkers included DNA ploidy, estrogen receptor (ER), and epidermal growth factor receptor (EGFR). The prevalence of DNA aneuploidy was 30%, overexpression of ER 10%, and overexpression of EGFR 35%, in the 206 high risk women whose median 10 year Gail risk (projected probability) of developing breast cancer was 4.5%. The prevalence of aneuploidy and overexpressed EGFR was significantly higher in the high risk women than in the 25 low risk controls (p < 0.002), whose median 10 year Gail risk was 0.7%. The difference in the prevalence of ER overexpression between high and low risk groups was not statistically significant (p = 0.095). This may be due to the low prevalence of overexpressed ER and the small number of controls. A significant difference was noted in the prevalence of one or more abnormal biomarkers between the high risk and low risk women (p < 0.001). A large prospective trial is needed to determine if one or more of these biomarkers, is predictive of breast cancer development.
Adult↗
Effect of long-term therapy with ramipril in high-risk women.
OBJECTIVES: We evaluated the effects of long-term therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on major cardiovascular (CV) outcomes in high-risk women. BACKGROUND: The effect of long-term ACE inhibitor therapy in high-risk women without heart failure and with preserved left ventricular (LV) systolic function has not been previously reported. METHODS: The Heart Outcomes Prevention Evaluation (HOPE) trial is a large, randomized clinical trial that evaluated ramipril and vitamin E in high-risk patients. We present the preplanned analysis of the effects of ramipril in women in the HOPE study. The study randomized 2,480 women aged >or=55 years with vascular disease or diabetes and at least one additional CV risk factor and without heart failure or a known low LV ejection fraction to ramipril (10 mg/day) or placebo. The primary outcome was the composite of myocardial infarction, stroke or CV death. Average follow-up was 4.5 years. RESULTS: Treatment with ramipril resulted in reduced primary end point rates (11.3% vs. 14.9% in the placebo arm; relative risk [RR] 0.77, 95% confidence interval [CI] 0.62 to 0.96; p = 0.019), fewer strokes (3.1% vs. 4.8%; RR 0.64, 95% CI 0.43 to 0.96; p = 0.029) and fewer CV deaths (4.2% vs. 6.9%; RR 0.62, 95% CI 0.44 to 0.88; p = 0.0068). There were trends toward reduced rates of myocardial infarction, heart failure and all-cause death. The beneficial effect of ramipril was similar in women and men. CONCLUSIONS: Treatment with ramipril reduces the CV risk in high-risk women without heart failure and with preserved LV systolic function.
Aged↗
Identification of a chemoprevention cohort from a population of women at high risk for breast cancer.
In a prospective pilot study, we performed breast fine needle aspirations (FNAs) on 213 high-risk and 30 low-risk women and analyzed these aspirates for cytologic changes and biomarker abnormalities of aneuploidy and overexpressed estrogen receptor (ER), epidermal growth factor receptor (EGFR), p53 and HER-2/neu. High-risk women were those with a first degree relative with breast cancer (73%), prior biopsy indicating premalignant breast disease (26%), a history of breast cancer (13%), or some multiple of these risk factors (11%). Median ages of the high-risk and low-risk groups were 44 and 42, respectively. Sixty-three percent of the high-risk and 73% of the low-risk group were premenopausal. Sixty-eight percent of the high-risk and 17% of low-risk women had cytologic evidence of hyperplasia with or without atypia (P < .0001). Aneuploidy and overexpression of EGFR and p53 occurred in 25%, 36%, and 28% of high-risk subjects but in less than 4% of low-risk subjects (P < .0002). Overexpression of ER and HER-2/neu occurred in 8% and 19%, respectively of high-risk women; nc low-risk women had these abnormalities. Sixty-eight percent of high-risk women and 7% of low-risk women had abnormalities of one or more of these biomarkers exclusive of cytology. Thirty-one percent of high-risk women, but no low-risk women had abnormalities of two or more biomarkers (P = .0004). Biomarker abnormalities were more frequent with increasing cytologic abnormality. Eighteen percent of women with normal cytology, 29% of women with epithelial hyperplasia and 60% of women with hyperplasia with atypia had abnormalities of two or more biomarkers (P = .048 and < .0001, respectively). Restricting the analysis to those three biomarkers most frequently overexpressed in the high-risk group (ploidy, EGFR, p53), 13% of high-risk women with normal cytology, 20% of high-risk women with epithelial hyperplasia and 51% of high-risk women with atypical hyperplasia had abnormalities of 2 or more of these 3 biomarkers. At a median follow up of two years, 8 of 213 women have been diagnosed with in situ (n = 5) or invasive (n = 3) cancer. Later detection of neoplasia was associated with prior FNA evidence of atypical hyperplasia (P < .0001) and multiple biomarker abnormalities in the 5 test battery (P = .006) by univariate analysis. By multivariate analysis, development and/or detection of cancer was primarily predicted by atypical hyperplasia (P = .0047) and secondarily by multiple biomarker abnormalities (P = 0.021). Atypical hyperplasia, EGFR, and p53 in breast FNAs have promise as risk markers and as surrogate endpoint biomarkers for breast cancer chemoprevention trials.
Adult↗
Hyperhomocysteinemia predicts total and cardiovascular mortality in high-risk women.
OBJECTIVE: The impact of homocysteine on cardiovascular disease can be more detrimental in women than in men, but it is unknown whether this applies to high-risk women. We therefore investigated the association of hyperhomocysteinemia with coronary artery disease (CAD) and cardiovascular mortality in high-risk women referred for CAD, both in the total population and in the hypertensive and normotensive cohorts. DESIGN: A prospective study cohort. SETTING: A tertiary centre. PATIENTS INCLUSION CRITERIA: 262 consecutive Caucasian postmenopausal women referred for coronary angiography. EXCLUSION CRITERIA: acute myocardial infarction and vitamin supplementation. MAIN OUTCOME MEASURE(S): We assessed total plasma homocysteine (tHcy), folate levels, and the MTHFR677C-->T polymorphism. CAD was defined as a modified Duke Index score greater than 0; hyperhomocysteinemia as tHcy levels of 15 micromol/l or greater. The primary study outcome was cardiovascular mortality at follow-up. RESULTS: Mild/moderate and severe hyperhomocysteinemia was found in 15.1 and 1.6% of women, respectively, without differences between CAD and non-CAD women. By the ATPIII criteria, 92.2% of the women were in the highest risk class and 55% had CAD; however, no association of tHcy with the CAD score was found. After a median follow-up of 3.6 years, 23 women (9.1%) had died, 15 (6%) of cardiovascular causes. Women with high tHcy levels showed the worst all-cause and cardiovascular death-free survival at Kaplan-Meier and Cox regression analysis. Moreover, in the hypertensive cohort only women with hyperhomocysteinemia showed increased cardiovascular mortality. CONCLUSION: Hyperhomocysteinemia is common in high-risk women and adversely affects their prognosis, although it is unrelated to the CAD atherosclerotic burden.
Aged↗