Acute toxicity patterns and their management after moderate and ultra- hypofractionated radiotherapy for prostate cancer: A prospective cohort study.

Objective: Hypofractionation has become the new clinical standard for prostate cancer. We investigated the management of acute toxicity in patients treated with moderate hypofractionation (MHF) or Ultrahypofractionation (UHF). Methods: In a prospective cohort setting, patients (N=316) received either MHF (20 fractions of 3/3.1 Gy, 5 fractions per week, N=156) or UHF (7 fractions of 6.1 Gy, 3 fractions per week, N=160) to the prostate +/- (base of the) seminal vesicles between 2019 and 2023. UHF was not indicated in case of significant lower urinary tract symptoms (LUTS) or T3b disease. Patient-reported outcomes (PRO) were online distributed at baseline, end of treatment (aiming at last fraction +/- 3 days), 3 months. Acute toxicity rates, management, and associations with baseline factors were analysed using Chi-square test and logistic regression. CTCAE scores (version 5) were calculated. Results: Treatment for acute urinary complaints was prescribed in 46 % (MHF) and 29 % (UHF). Taking into consideration baseline LUTS, MHF and UHF showed similar rates of PROs and management. Medication for acute gastrointestinal (GI) symptoms was prescribed for 21.1 % (MHF) and 14.1 % (UHF) with more loperamide for diarrhea in MHF (9.0 %) vs UHF (1.9 %, p = 0.005). Grade ≥ 2 (MHF / UHF) was scored in 40 % / 28 % for GI (p = 0.03) and 50 % / 31 % for GU (p < 0.01). PROs for GI reported after last fraction of UHF were significantly worse compared to before last fraction. Conclusion: UHF was safe with respect to acute toxicity risks in the selected population. MHF is associated with risks of significant diarrhea which needs further investigation. Furthermore, optimal registration of acute toxicity for UHF requires measurements up to 1-2 weeks after the last fraction.

Brachytherapy quality assurance in the PORTEC-4a trial for molecular-integrated risk profile guided adjuvant treatment of endometrial cancer.

OBJECTIVE: The PORTEC-4a trial investigates molecular-integrated risk profile guided adjuvant treatment for endometrial cancer. The quality assurance programme included a dummy run for vaginal brachytherapy prior to site activation, and annual quality assurance to verify protocol adherence. Aims of this study were to evaluate vaginal brachytherapy quality and protocol adherence. METHODS: For the dummy run, institutes were invited to create a brachytherapy plan on a provided CT-scan with the applicator in situ. For annual quality assurance, institutes provided data of one randomly selected brachytherapy case. A brachytherapy panel reviewed and scored the brachytherapy plans according to a checklist. RESULTS: At the dummy run, 15 out of 21 (71.4%) institutes needed adjustments of delineation or planning. After adjustments, the mean dose at the vaginal apex (protocol: 100%; 7 Gy) decreased from 100.7% to 99.9% and range and standard deviation (SD) narrowed from 83.6-135.1 to 96.4-101.4 and 8.8 to 1.1, respectively. At annual quality assurance, 22 out of 27 (81.5%) cases had no or minor and 5 out of 27 (18.5%) major deviations. Most deviations were related to delineation, mean dose at the vaginal apex (98.0%, 74.7-114.2, SD 7.6) or reference volume length. CONCLUSIONS: Most feedback during the brachytherapy quality assurance procedure of the PORTEC-4a trial was related to delineation, dose at the vaginal apex and the reference volume length. Annual quality assurance is essential to promote protocol compliance, ensuring high quality vaginal brachytherapy in all participating institutes.

A review of interprofessional training wards: Enhancing student learning and patient outcomes.

Background: In an interprofessional training ward (ITW), students from different health professions collaboratively perform patient care with the goal of improving patient care. In the past two decades, ITWs have been established world-wide and studies have investigated their benefits. We aimed to compare ITWs with respect to their logistics, interprofessional learning outcomes and patient outcomes. Methods: We explored PubMed, CINAHL, Web of Science and EMBASE (1990-June 2017) and included articles focusing on interprofessional, in-patient training wards with student teams of medical and other health professions students. Two independent reviewers screened studies for eligibility and extracted data. Results: Thirty-seven articles from twelve different institutions with ITWs were included. ITWs world-wide are organized similarly with groups of 2-12 students (i.e. medical, nursing, physiotherapy, occupational therapy, and pharmacy) being involved in patient care, usually for a period of two weeks. However, the type of clinical ward and the way supervisors are trained differ. Conclusions: ITWs show promising results in short-term student learning outcomes and patient satisfaction rates. Future ITW studies should measure students' long-term interprofessional competencies using standardized tools. Furthermore, a research focus on the impact of ITWs on patient satisfaction and relevant patient care outcomes is important.

Molecular-integrated risk profile to determine adjuvant radiotherapy in endometrial cancer: Evaluation of the pilot phase of the PORTEC-4a trial.

OBJECTIVE: The Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-4a trial is a randomized trial for women with high-intermediate risk endometrial cancer (EC), comparing individualized adjuvant treatment based on a molecular-integrated risk profile to standard adjuvant treatment; vaginal brachytherapy. To evaluate patient acceptability and pathology logistics of determining the risk profile, a pilot phase was included in the study. METHODS: PORTEC-4a is ongoing and the first 50 patients enrolled were included in the pilot phase. Primary endpoints of the pilot phase were patient acceptance, evaluated by analyzing the screening logs of the participating centers, and logistical feasibility of determination of the risk profile within 2 weeks, evaluated by analyzing the pathology database. RESULTS: In the first year, 145 eligible women were informed about the trial at 13 centers, of whom 50 (35%) provided informed consent. Patient accrual ranged from 0 to 57% per center. Most common reasons for not participating were: not willing to participate in any trial (43.2%) and not willing to risk receiving no adjuvant treatment (32.6%). Analysis of the pathology database showed an average time between randomization and determination of the molecular-integrated risk profile of 10.2 days (1-23 days). In 5 of the 32 patients (15.6%), pathology review took >2 weeks. CONCLUSIONS: The PORTEC-4a trial design was proven feasible with a satisfactory patient acceptance rate and an optimized workflow of the determination of the molecular-integrated risk profile. PORTEC-4a is the first randomized trial to investigate use of a molecular-integrated risk profile to determine adjuvant treatment in EC.

Cardiovascular and metabolic characteristics of infertile Chinese women with PCOS diagnosed according to the Rotterdam consensus criteria.

Polycystic ovary syndrome (PCOS) is strongly associated with metabolic abnormalities in Western women. However, data from other populations and geographical regions are scarce. This study evaluated cardiovascular and metabolic risk factors in Chinese infertile women diagnosed with PCOS using the 2003 Rotterdam consensus criteria. A total of 615 women representing the four PCOS phenotypes (oligo- or anovulation (AO)+hyperandrogenism (HA)+polycystic ovaries (PCO), AO+HA, AO+PCO and HA+PCO) underwent standardized metabolic screening including a 75g oral glucose tolerance test. All groups presented with similar reproductive characteristics, with the only difference being a significantly higher Ferriman-Gallwey score for hirsutism (P=0.01) in the subgroup characterized by HA+PCO. Overall, the prevalence of metabolic syndrome was 6.4%, with no difference among the four groups (range of 2.3-12.2%). Metabolic syndrome was associated with body mass index (P<0.001), waist/hip ratio (P=0.002), index of insulin resistance (P=0.005) and fasting insulin (P=0.009) in multivariate analysis. Compared with Caucasians and Chinese women in Westernized societies, mainland Chinese women with PCOS have a low risk of metabolic syndrome and its presence does not vary across the specific PCOS phenotypes.

Polycystic ovary syndrome and early-onset preeclampsia: reproductive manifestations of increased cardiovascular risk.

OBJECTIVE: Primary prevention of cardiovascular disease (CVD) in women is a major healthcare issue. Detection of premenopausal women with increased risk of CVD could enhance prevention strategies and reduce first event-related morbidity and mortality. In this study, we argue that an unfavorable metabolic constitution in women may present itself early in life as a reproductive complication, such as polycystic ovary syndrome (PCOS) and preeclampsia. We evaluated the cardiovascular risk of women with a history of early-onset preeclampsia and women with PCOS and assessed their need for implementation of early risk factor-reduction strategies. METHODS: We performed a standardized evaluation of 240 women with a history of early-onset preeclampsia and 456 women diagnosed with PCOS for established major CVD risk factors. Metabolic syndrome characteristics were analyzed per body mass index category. RESULTS: Mean age was 30.6 and 29.0 years for women with preeclampsia and PCOS, respectively. High percentages of metabolic syndrome were found in both groups (preeclampsia group, 14.6%; and PCOS group, 18.4%), with an incidence of greater than 50% in both groups of women if body mass index was greater than 30 kg/m. Overall, more than 90% of the women qualified for either lifestyle or medical intervention according to the American Heart Association guideline for CVD prevention in women. CONCLUSIONS: Women with PCOS and early-onset preeclampsia already show an unfavorable cardiovascular risk profile with high need for lifestyle or medical intervention at a young age. We therefore recommend an active role of the gynecologist in routine screening and follow-up of women with reproductive conditions linked to future cardiovascular risk.

Indicators for metabolic disturbances in anovulatory women with polycystic ovary syndrome diagnosed according to the Rotterdam consensus criteria.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with metabolic abnormalities. It is debated whether all women with PCOS should be screened for metabolic abnormalities as these may vary with PCOS phenotype, age and ethnicity. The aims of this study were to assess the prevalence of metabolic abnormalities in Dutch anovulatory PCOS women and to define criteria for metabolic screening. METHODS: Anovulatory patients, diagnosed with PCOS according to the Rotterdam consensus criteria, underwent metabolic screening. Through stepwise multivariate analysis patient characteristics associated with metabolic syndrome (MetS) and insulin resistance (IR) were evaluated for their use as selection parameters for metabolic screening. RESULTS: Overall, prevalence of MetS and IR was 15.9% (n = 25) and 14% (n = 22), respectively, in 157 PCOS women (age 29.0 +/- 4.8 years, BMI 26.1 +/- 6.7 kg/m(2)). Anovulatory hyperandrogenic women (with or without polycystic ovaries) had more often MetS and IR (with, 20.8 and 19.8%; without, 100 and 40%, respectively) than non-hyperandrogenic PCOS women (0 and 1.8%; P < 0.001). Waist circumference >83.5 cm along with increased free androgen index (FAI) had the most powerful association with the presence of MetS and IR (area under the receiver operating characteristic curve 0.912) and offered a reduction in the necessity of screening for metabolic derailments of about 50%. CONCLUSIONS: The hyperandrogenic PCOS phenotypes are highly linked to the presence of MetS and IR in Dutch PCOS women. Waist circumference combined with FAI was identified as an efficient combination test to select those PCOS women who should be screened for the presence of MetS and/or IR.

Cardiometabolic abnormalities in the polycystic ovary syndrome: pharmacotherapeutic insights.

The polycystic ovary syndrome (PCOS) affects 5-10% of all premenopausal women. It is diagnosed by a combination of oligo-amenorrhea and hyperandrogenism (NIH criteria) or by the presence of two out of three of: oligo-amenorrhea, hyperandrogenism, polycystic ovaries on ultrasound (Rotterdam criteria). PCOS is associated with obesity, insulin resistance and dyslipidemia. Different patterns of dyslipidemia can be present, both in lean and obese PCOS. Low HDL-cholesterol, with or without elevated TG, is the most prominent lipid abnormality. In addition, smaller HDL and LDL particles and elevated postprandial TG responses are reported. Hyperandrogenism, anovulation and insulin resistance affect multiple steps in lipid metabolism in PCOS, as will be discussed. Surrogate markers for atherosclerosis are consistently abnormal in PCOS, while studies on clinical CVD endpoints are limited and non-conclusive. The (pharmaco-) therapy of dyslipidemia in PCOS will be discussed. In addition, the effects of other PCOS related (pharmaco-) therapies, primarily aimed at hyperandrogenism, anovulation or insulin resistance, on lipid metabolism will be addressed.

[Women and cardiovascular disease]. / Vrouwen en hart- en vaatziekten.

More women die of cardiovascular disease than men; in women, cardiovascular mortality is 1.5 times greater than cancer mortality. The pathophysiology of cardiovascular disease has female-specific aspects such as fragile coronary arteries and microvascular ischaemia. Women with acute coronary syndromes are more likely to present with atypical symptoms such as dyspnoea, nausea or fatigue. With regard to diagnostic tests in women, exercise ECG can be difficult to interpret and a normal coronary angiogram does not exclude coronary heart disease. Myocardial perfusion scintigraphy may be considered for high-risk women who are clinically suspected of having coronary heart disease and have a normal or inconclusive exercise ECG and angiogram. Women are less likely to be treated according to guidelines than men, and their prognosis after a myocardial infarction or a coronary intervention is worse. Female-specific aspects such as gestational hypertension and diabetes allow for early detection and treatment of women at risk for cardiovascular disease.

Dutch medical oath.

In the first part of this article, the booklet Dutch Medical Oath is reviewed. The content of the new oath is discussed as are the reasons for revision of the previous version of the oath. This is followed by a short history of the oath. In the second part of the article the oath is compared with the seven competencies of a medical specialist. The new oath contains elements of six of these seven competencies. This demonstrates that the oath is in keeping with the new medical educational demands.

Treatment with hormone replacement therapy lowers remnant lipoprotein particles in healthy postmenopausal women: results from a randomized trial.

BACKGROUND: Recent evidence indicates that remnant lipoprotein particles (RLPs) may play a role in atherosclerosis. Remnant lipoprotein particles have been suggested to be the most atherogenic particles among the triglyceride-rich lipoproteins. In particular, these triglyceride-rich particles were identified as an independent risk factor for cardiovascular diseases (CVD) in women. Postmenopausal hormone replacement therapy (HRT) beneficially affects lipid profile, although total triglyceride levels often increase. Evidence on the effects of HRT on RLPs is limited. We determined whether 3 months' treatment of postmenopausal women with Tibolone or conjugated oestrogens combined with medroxyprogesterone acetate (CEE + MPA) affects RLP-cholesterol (RLP-C). MATERIALS AND METHODS: One hundred and five healthy postmenopausal women were randomized to either 2.5 mg of Tibolone, 0.625 mg of CEE + 2.5 mg of MPA or placebo. At baseline and after 3 months the lipid profile was determined. For assessment of RLP-C we used an immunoseparation-based method. RESULTS: Treatment with CEE + MPA significantly reduced RLP-C (-0.03 mmol L-1, P-value = 0.01) and appeared to increase triglycerides (0.15 mmol L-1, P-value = 0.20) compared with placebo. Tibolone did not significantly change RLP-C (-0.01 mmol L-1, P-value = 0.35) and significantly decreased triglycerides (-0.35 mmol L-1, P-value = 0.004). CONCLUSIONS: Treatment of postmenopausal women with conjugated oestrogens and medroxyprogesterone acetate reduced RLP-C, without a reduction in total triglycerides, whereas Tibolone did affect triglyceride levels, but not RLP-C. These observations may be relevant for explaining the effect of HRT on cardiovascular risk in healthy postmenopausal women.

Plasma and urinary sex hormones are differently related to lipids in healthy postmenopausal women.

OBJECTIVE: Endogenous sex hormones can be measured in plasma and urine. We determined the extent to which these two methods provide different information on hormonal status by relating them to lipid profile in postmenopausal women. METHODS: Thirty healthy postmenopausal women collected one 24-h urine sample and a blood sample was taken. Urinary estrone (UE), plasma estrone (PE) and serum lipids were measured. Sex hormone levels were measured with specific radioimmunoassays. Linear regression analysis was used to determine associations between estrone levels and lipids. Results are presented as beta-coefficients in mmol/l per standard deviation (SD) of endogenous estrone levels, adjusted for body mass index (BMI) and smoking (95% confidence interval). A stratified analysis for obese (BMI> or =27 kg/m(2)) versus lean women was performed. RESULTS: Mean levels of endogenous sex hormones were (SD): PE, 90.1 pmol/l (37.3); and UE, 7757 pmol/24 h (2659). PE showed significant associations with HDL-cholesterol (0.18 mmol/l, 95% CI: 0.06; 0.30), triglycerides (-0.25 mmol/l, 95% CI: -0.49; -0.009) and very-low-density-lipoprotein (VLDL-cholesterol) (-0.11 mmol/l, 95% CI: -0.22; -0.003), but not with total and low-density-lipoprotein (LDL-cholesterol). UE was inversely associated with total (-0.41 mmol/l, 95% CI: -0.85; 0.02) and LDL-cholesterols (-0.42 mmol/l, 95% CI: -0.83; -0.005), but not with HDL-cholesterol, triglycerides and VLDL-cholesterol. All associations appeared to be stronger in lean women. CONCLUSION: Both plasma and UE levels appear to be associated to serum lipids in healthy postmenopausal women. However, this relation appears to be different for estrone levels in plasma and urine. Depending on the research question, either blood samples or urine samples may be preferred.

Risk factors for coronary heart disease: implications of gender.

It has been recognized over the past years that women form a distinct subpopulation within patients with coronary heart disease. This phenomenon should be acknowledged in the management and in the assessment of coronary heart disease. Over the past years remarkable progress has been made concerning our knowledge of cardiovascular risk factors related to gender. For instance, diabetes, high density lipoproteins and triglycerides levels have been found to have a greater impact on coronary heart disease risk in women compared to men. On the other hand, evidence showing that lipoprotein (a) is a cardiovascular risk factor seems to be stronger in men than in women. For optimal treatment and prevention of coronary heart disease it is necessary to acknowledge that it is not self-evident that women and men show similar responses to risk factors or to treatment. This review article addresses the role of cardiovascular risk factors focusing on the differential impact they might have on men and women.

Differential effect of female gender on coronary artery disease and peripheral artery disease.

BACKGROUND: Women are relatively protected against coronary artery disease (CAD). Whether female gender has a similar protective influence on the development of peripheral artery disease (PAD) has not been extensively investigated and was the main subject of our study. METHODS: We analysed 2707 consecutive patients (2008 men and 699 women) who underwent a first diagnostic coronary angiography for suspicion of CAD and 2367 consecutive patients (1426 men and 941 women) who underwent a first ankle arm index measurement because of suspicion of PAD. RESULTS: We found that a positive diagnosis for CAD and PAD was more common in men compared with women (80.7% vs 57.9%, p<0.0001 and 68.0% vs 60.7%, p<0.0001). Once CAD or PAD was established, severity of disease was similar for men and women, which pleads against a referral bias. Women had a reduced risk of CAD after adjustment for risk factors (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.22-0.46, p<0.0001), but not of PAD (OR 0.82, 95% CI 0.66-1.03, p=NS). In patients with CAD and in those with PAD, women were older, more often had diabetes and hypertension, while men were more likely to be current smokers. Hypertension, smoking and diabetes were associated with CAD in both men and women. Current smoking was associated with PAD in men and women. Hypertension and diabetes were associated with PAD in women but not in men. CONCLUSION: After adjustment for risk factors, the female protection for CAD seems to less present for PAD.

Apolipoprotein concentrations during treatment and recurrent coronary artery disease events.

The effect of untreated total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) as cardiovascular risk factors in both primary and secondary prevention has been extensively investigated. The predictive value of on-treatment lipid and apolipoprotein levels on subsequent cardiovascular events is as yet uncertain. Eight hundred forty-eight patients (675 men and 173 women) with angiographically proven coronary artery disease (CAD) who received effective statin therapy (>/=30% decrease of baseline TC) were studied. We analyzed the predictive value of on-treatment levels of TC, LDL-C, triglycerides (TG), apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) on subsequent myocardial infarction (MI) and all cause mortality. On-treatment LDL-C levels were 2.55+/-0.55 mmol/L and 2.58+/-0.62 mmol/L for men and women respectively. Age-adjusted Cox regression analysis showed that only on-treatment apoA-I was predictive for future CAD events in both men and women, whereas on-treatment HDL-C was exclusively predictive in women. On-treatment apoB levels were predictive for recurrent CAD events in the total population but not after separate analysis for men and women. On-treatment levels of TC, LDL-C, and TG did not predict subsequent events. Multivariate analysis showed that on-treatment apoA-I and apoB were the only significant predictors for future cardiovascular events. On-treatment levels of TC, LDL-C, and TG were no longer associated with increased risk of recurrent cardiovascular events in CAD patients treated to target levels, which justifies the current guidelines. However, on-treatment levels of apoB and in particular apoA-I (and HDL-C in women) were significantly predictive for MI and all-cause mortality and may therefore be more suitable for cardiovascular risk assessment in this population.

Gender differences in diagnosis and treatment of coronary artery disease from 1981 to 1997. No evidence for the Yentl syndrome.

AIMS: The aim of the present clinical study was to evaluate whether gender-related differences existed as regards the extent and localization of coronary artery lesions in patients with angiographically documented coronary artery disease, and whether these angiographic findings would lead to differences in further management. METHODS AND RESULTS: Over a 16-year period (1981-1997) we evaluated 1894 patients (1526 men, 368 women) with angiographically documented coronary artery disease (luminal stenosis >/=60%). For each patient the coronary angiographic results and subsequent revascularization procedures (percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery) were analysed. The study period was divided into the early angioplasty years (1981 to 1989) and the current angioplasty years (1990-1997). No gender differences in extent and localization of coronary angiographic lesions were observed. In men and women the incidence of single-vessel disease was 42% and 40%, two-vessel disease 27% and 27%, three-vessel disease 26% and 24%, and left main disease 5% and 8%, respectively (P=ns). Localization of disease in men and women was 36% and 39% for the left anterior descending coronary artery, 34% and 32% for the right coronary artery, and 27% and 26% for the left circumflex coronary artery, respectively (P=ns). There was a significant shift from multi-vessel disease towards single-vessel disease in both men and women (both P<0.001). As to subsequent management, a significant gender difference in favour of women was observed (P=0.021). Over time, the number of angioplasty procedures increased significantly from 11.6% to 23.2% for men (P<0.001), and for women from 17.6% to 28.0% (P=0.025), whereas the number of coronary artery bypass procedures decreased in men from 34.9% to 29. 5% (P=0.024) and in women from 42.6% to 30.6% (P=0.019). Referral to angioplasty (n=535) and coronary artery bypass surgery (n=616) in relation to the extent of the disease did not show any gender bias in favour of men. CONCLUSIONS: Our angiographic findings did not show significant gender differences as regards the extent and localization of coronary artery disease in patients with angiographically documented coronary artery disease. More importantly, no substantial evidence could be found for under-referral of women to subsequent therapeutic management. Therefore our study questions the presence of Yentl syndrome in the current era.

Delayed chylomicron remnant clearance in subjects with heterozygous familial hypercholesterolaemia.

OBJECTIVES: To study the role of the LDL receptor in the clearance of chylomicron remnants in humans. DESIGN: Chylomicron remnant clearance was studied in five untreated subjects with heterozygous familial hypercholesterolaemia (FH) and nine normolipidaemic controls, by oral retinyl palmitate-fat loading tests. Fasting plasma triglycerides (TG), which are important determinators of chylomicron and remnant clearance, were not significantly different between FH (1.76+/-0.32 mmol L(-1), mean+/-SEM) and controls (1.26+/-0.18 mmol L(-1). Chylomicrons (Sf > 1000) and their remnants (Sf < 1000) were separated by flotation and their clearance was estimated by calculating the area under the 24 h-retinyl palmitate curve (AUC-RP). The factors determining chylomicron and remnant clearance were studied by univariate and multiple regression analysis. RESULTS: Triglyceride clearance in plasma, Sf > 1000 fractions and Sf < 1000 fractions was not significantly different between FH subjects and controls. In subjects with heterozygous FH, chylomicron remnant clearance was two-fold delayed (AUC-RP, 49.39+/-11.61 h.mg L(-1) compared to controls (27.45+/-3.95 h.mg L(-1); P = 0.048). Moreover, 28.4% higher fasting plasma TG in FH resulted in 44.4% higher areas under the remnant-curves compared to controls. The clearance of chylomicron RP was associated to plasma apo E (beta = 0.73, P = 0.011), plasma LDL cholesterol (beta = 0.62, P = 0.018) and plasma TG (beta = 0.58, P = 0.029). The clearance of remnant RP was associated to the diagnosis (FH vs. non-FH), but not to the well-known determinants of remnant clearance like plasma TG. CONCLUSIONS: The clearance of chylomicrons and large remnants isolated in the Sf > fraction depends primarily on the apo B, E (LDL) receptor and to a lesser extent on plasma triglycerides. The clearance of smaller chylomicron remnants isolated in the Sf < 1000 depends to a large extent on the apo B, E (LDL) receptor.

Apolipoprotein B and coronary artery disease in women: a cross-sectional study in women undergoing their first coronary angiography.

The association between plasma apolipoprotein (apo) B concentrations and angiographically determined coronary artery disease (CAD) was investigated in women in a cross-sectional study. Stenosis of >60% in 1 or more coronary arteries was classified as CAD+. CAD- was defined as a maximum stenosis of 10% in any coronary artery. Fasting plasma concentrations of apoB, apoA-I, cholesterol (chol), low density lipoprotein cholesterol (LDL-chol), high density lipoprotein cholesterol (HDL-chol), and triglycerides (TGs) were determined. Information on nonlipid risk factors was obtained from questionnaires. CAD+ women (n=160) were older than CAD- women (n=129), 64.0+/-7.8 vs 57.8+/-11.1 years, respectively. CAD+ compared with CAD- women had higher frequencies of diabetes (14.7% vs 5.8%, P=0.05), hypertension (53% vs 37%, P=0.018), and ever-smoking (48% vs 35%, P<0.001). CAD+ women had higher plasma concentrations of apoB (1.48+/-0.32 vs 1.25+/-0.34 g/L, P<0.001), chol (7.01+/-1.19 vs 6.38+/-1.22 mmol/L, P=0.001), LDL-chol (4.74+/-1.09 vs 4.13+/-1.13 mmol/L, P<0.001), and TGs (1.98+/-0.84 vs 1.71+/-0.93 mmol/L, P=0.007) and lower levels of HDL-chol (1.28+/-0.28 vs 1.37+/-1.38 mmol/L, P=0.028). After correction for nonlipid risk factors, apoB, chol, LDL-chol, HDL-chol, and TG were independently related to CAD. In the lowest quartiles of chol, LDL-chol, and TG, CAD+ women had higher apoB concentrations than CAD- women. In contrast, chol, LDL-chol, TG, or HDL-chol levels were not different in any quartile of apoB. ApoB showed the most significant relation with the number of stenotic vessels, and apoB was associated with CAD in the normolipidemic subgroup. In conclusion, apoB was superior to chol, LDL-chol, HDL-chol, TG, and apoA-I in discriminating between CAD+ and CAD-.

Estrogens and postprandial lipid metabolism.

Women with angiographically proven coronary heart disease (CAD) had higher postprandial concentrations of small chylomicron-remnants, measured as IDL apo B48, than women without CAD. Fasting TG concentrations were not different and within the normal range. Thus, the postprandial concentration of small chylomicron-remnants could identify women at high CAD risk within a normolipidemic population. Replacement therapy with 17beta-estradiol improved the clearance of chylomicron-remnants by 41% and attenuated the postprandial reduction in HDL-cholesterol by 66%. This improvement in postprandial lipid metabolism can explain part of the protective effect of estrogens against CAD.