Low serum cholesterol concentration and serotonin metabolism in men.
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Biomedical subjects
D E Grobbee
Publications and source records attributed to D E Grobbee.
Age-related macular degeneration and smoking. The Rotterdam Study.
OBJECTIVE: To assess the relation between cigarette smoking and age-related macular degeneration (AMD) in a population of elderly persons. DESIGN: A cross-sectional, community-based study. SETTING: City district of Rotterdam, the Netherlands. PARTICIPANTS: A total of 6174 persons 55 years and older who participated in the Rotterdam Study. In 36 persons atrophic AMD and in 65 persons neovascular AMD were diagnosed. MAIN OUTCOME MEASURES: Age-related macular degeneration was diagnosed by evaluating fundus transparencies, smoking behavior was identified by interviewing subjects, and the presence of atherosclerosis was assessed by the ankle-arm systolic blood pressure index. Relative risks and 95% confidence intervals (CIs) were calculated using multivariate logistic regression analysis. RESULTS: In subjects younger than 85 years, current smokers had a 6.6-fold increased risk of neovascular AMD vs those who had never smoked (95% CI, 2.8-15.9). Former smokers had a 3.2-fold increased risk of neovascular AMD vs nonsmokers in this age group (95% CI, 1.4-7.4). These associations were not observed in subjects 85 years or older. Smoking was not associated with atrophic AMD. A strong increased risk of neovascular AMD was present in those who had smoked more than 10 pack-years (relative risk, 6.5; 95% CI, 2.9-14.8). Adjusting the results for atherosclerosis did not change the association. Persons who had quit smoking 20 or more years before the eye examination had no increased risk. CONCLUSIONS: The results provide evidence for a dose-response relationship between smoking and AMD, particularly in persons with the neovascular form of the disease.
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Transrectal ultrasonic volumetry of the prostate: in vivo comparison of different methods.
In order to assess the accuracy of various volumetric methods for screening and follow-up of prostatic disease, total prostate volume and inner zone volume were measured by transrectal ultrasonography in a screening population of 716 men. Semiplanimetric and caliper formula methods were compared with step section planimetry as the gold standard. Planimetric volumetry of the prostate is regarded as the most reproducible method for individual follow-up of total gland and inner zone volume. The prolate spheroid formula is the most reproducible of caliper formula methods for both volumes. In this study the elliptical volume was, however, more accurate than the prolate spheroid volume of the total gland, as the correlation coefficient between total elliptical volume and planimetry was higher compared to the prolate spheroid volume (0.89 vs. 0.83), and the standard deviation of the mean volumetric difference smaller. The mean total prolate spheroid volume resembled the mean total planimetric volume better than the elliptical volume did, as the mean volumetric difference was smaller. For measurement of the inner zone volume the prolate spheroid volume was more accurate that the elliptical volume. The correlation coefficient between length and planimetric volume was similar to that of width and height, which accounted for more accuracy of the elliptical volume that of the prolate spheroid volume in larger prostates. The elliptical volume might be used for incidental volumetric measurements of the total gland, and for comparison of different individuals, e.g., in preoperative evaluation or screening studies.
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Association of radiographically evident osteoarthritis with higher bone mineral density and increased bone loss with age. The Rotterdam Study.
OBJECTIVE: To investigate the relationship of osteoarthritis (OA) to bone mineral density (BMD) and rate of bone loss. METHODS: The study group consisted of 2,745 persons (1,624 women) from the general elderly population. Disability was assessed by the Health Assessment Questionnaire. Femoral neck BMD was measured at baseline and, in 1,723 subjects, after 2 years of followup. Knee and hip radiographic OA was assessed on anteroposterior radiographs. RESULTS: With the exception of knee radiographic OA in men, radiographic OA was associated with significantly increased BMD (3-8%). BMD increased significantly according to the number of affected sites and the Kellgren score. Radiographic OA was also associated with significantly elevated bone loss with age (in men, only for radiographic OA of the hip). A significant increase in relation to the number of affected sites and the Kellgren score (except with regard to knee OA in men) was found, independent of disability. CONCLUSION: Radiographic OA is associated with high BMD and increased rate of bone loss. This suggests a more pronounced difference in BMD earlier in life.
Age Factors↗
Vascular risk factors, atherosclerosis, cerebral white matter lesions and cerebral perfusion in a population-based study.
We studied risk factors for cerebral vascular disease (blood pressure and hypertension, factor VIIc, factor VIIIc, fibrinogen), indicators of atherosclerosis (intima-media thickness and plaques in the carotid artery) and cerebral white matter lesions in relation to regional cerebral blood flow (rCBF) in 60 persons (aged 65-85 years) recruited from a population-based study. rCBF was assessed with single-photon emission tomography using technetium-99m d, l-hexamethylpropylene amine oxime (99mTc-HMPAO). Statistical analysis was performed with multiple linear regression with adjustment for age, sex and ventricle-to-brain ratio. A significant positive association was found between systolic and diastolic blood pressure and temporo-parietal rCBF. In analysis with quartiles of the distribution, we found a threshold effect for the relation of low diastolic blood pressure (</=60 mmHg) and low temporo-parietal rCBF. Levels of plasma fibrinogen were inversely related to parietal rCBF, with a threshold effect of high fibrinogen levels (>3.2 g/l) and low rCBF. Increased atherosclerosis was related to low rCBF in all cortical regions, but these associations were not significant. No consistent relation was observed between severity of cerebral white matter lesions and rCBF. Our results may have implications for blood pressure control in the elderly population.
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Association of diabetes mellitus and dementia: the Rotterdam Study.
Dementia and non-insulin-dependent diabetes mellitus (NIDDM) are highly prevalent disorders in the elderly. Diabetes has repeatedly been reported to affect cognition, but its relation with dementia is uncertain. We therefore studied the association between diabetes and dementia in the Rotterdam Study, a large population-based study in the elderly. Of 6330 participants, aged 55 to 99 years old, complete information on diabetes and presence of dementia was available. Diabetes was diagnosed as use of anti-diabetes medication or random or post-load serum glucose over 11 mmol/1. Dementia was diagnosed through a stepped approach, including a sensitive screening of all participants and a comprehensive diagnostic work-up. Diabetes was present in 724 (11.4%) subjects. Of the 265 dementia patients 59 (22.3%) had diabetes. Multiple logistic regression analyses, adjusting for age and sex differences, revealed a positive association between diabetes and dementia (odds ratio: 1.3, 95% confidence interval 1.0-1.9). In particular, strong associations were found between dementia and diabetes treated with insulin (odds ratio: 3.2, 95% confidence interval: 1.4-7.5) The relation was strongest with vascular dementia but was also observed with Alzheimer's disease. These associations were independent of educational attainment, smoking, body mass index, atherosclerosis, blood pressure and antihypertensive drug treatment, and could not be explained by clinical cerebra infarctions. The results suggest that NIDDM is associated with dementia. Alzheimer's disease may be more frequent in elderly diabetic patients treated with insulin.
Age Factors↗
Vitamin K status and bone mass in women with and without aortic atherosclerosis: a population-based study.
Gammacarboxyglutamate (Gla) is an uncommon amino acid formed by vitamin K action. Increasing evidence indicates that Gla-proteins are involved in the regulation of calcification processes in both bone tissue and atherosclerotic vessel wall. In a population-based study we have previously shown that in a group of 113 postmenopausal women the presence of abdominal aortic calcifications is associated with a reduced vitamin K status. In the present study we investigated whether this reduced vitamin K status was also associated with differences in bone mass or circulating calciotropic hormone levels. Serum immunoreactive osteocalcin with low affinity for hydroxyapatite (irOCfree) was used as a marker for vitamin K status. After correction for age it was found that women with atherosclerotic calcifications had a 7% lower bone mass as measured by metacarpal radiogrammetry (mean difference: 3.2 mm2, 95% CI: -0. 2-6.5, P = 0.06). No differences between both groups of women were observed for serum intact parathyroid hormone (PTH) and serum 25-hydroxyvitamin D levels. In the atherosclerotic women (n = 34), markers for vitamin K status were inversely associated with bone mass (r = -0.47, P = 0.013), whereas no such association was found in the nonatherosclerotic women (n = 79). It is concluded that the atherosclerotic women in this study may be at higher risk for osteoporotic fractures as evidenced by their lower bone mass and higher serum irOCfree levels. The finding that in atherosclerotic women vitamin K status is associated with bone mass supports our hypothesis that vitamin K status affects the mineralization processes in both bone and in atherosclerotic plaques.
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Pattern of sumatriptan use and overuse in general practice.
OBJECTIVE: To investigate the frequency of use and misuse of sumatriptan, and to explore the characteristics of patients reporting overuse. SETTING: A postmarketing cohort study on adverse reactions to sumatriptan, performed with the assistance of drug-dispensing general practitioners in the Netherlands. METHODS: Questionnaires were sent to patients on sumatriptan of drug-dispensing general practitioners in the Netherlands. Use of sumatriptan was classified into five groups: < 1, 1-10, 11-20 and 21-30 times per month and a group of patients who reported daily use of sumatriptan more than 10 times per week. Patients in the latter group were regarded as "overusers". RESULTS: The request to the 1720 patients yielded a response rate of 1202 (70%). Of 952 (79%) of these patients, details of their sumatriptan intake were available. Most patients (718, 75%) took sumatriptan 1-10 times each month. However, 36 patients (4%, 95% CI 2.8-5.2%) took sumatriptan daily or more than 10 times each week. The group with the highest intake consisted mainly of males, and many patients who reported a poor efficacy of sumatriptan. Age was not related to use of sumatriptan. CONCLUSIONS: A small group of patients (4%) used sumatriptan too often. A high intake was associated with both male gender and a reported poor efficacy of sumatriptan, but not with age, reported adverse reactions, or headache attributed to sumatriptan. It is important to explain to patients that sumatriptan is only for the treatment of acute attacks, and not for prophylactic use. Drug consumption patterns have to be evaluated, in particular in patients who report low efficacy of sumatriptan.
Administration, Oral↗
Lipoproteins and apolipoproteins in the young and familial risk of coronary atherosclerosis.
The aim of this study was to assess the predictive value of lipoproteins and apolipoproteins at a young age for the development of coronary artery disease at middle and older ages. Because children of coronary artery disease patients are at high risk themselves we compared lipoprotein and apolipoprotein levels between the offspring of parents with and without coronary artery disease. We selected a group of male patients (n = 90), who had severe coronary atherosclerosis at angiography, and a reference group of male controls (n = 62), who had no coronary atherosclerosis at angiography. Lipoprotein and apolipoprotein levels were determined in 115 sons and 73 daughters of the patients with severe coronary atherosclerosis. These were compared to levels in 68 sons and 47 daughters of controls. Additionally, lipoprotein and apolipoprotein levels were compared between patients and controls as well as between their spouses. In sons of patients, lower levels of HDL3 cholesterol (-0.07 mmol/1, standard error of the mean (SEM) 0.03, P < 0.05) and apolipoprotein A2 (-5.1 mg/dl (SEM, 1.4), P < 0.0001) were found compared to sons of controls. Similar differences were observed in daughters of such patients without, however, achieving statistical significance. No significant differences between the groups of offspring were found for total cholesterol, LDL cholesterol, HDL and HDL2 cholesterol, triglycerides and apolipoproteins A-I and B. Patients had higher levels of total (group difference 0.6 mmol/1 (SEM, 0.18), P < 0.001) and LDL cholesterol (0.6 mmol/1 (SEM, 0.17), P < 0.001), triglycerides (0.6 mmol/1 (SEM, 0.16), P < 0.001) and apolipoprotein B (21.2 mg/dl (SEM, 5.1), P < 0.001), and lower HDL cholesterol (0.1 mmol/1 (SEM, 0.04), P < 0.05) than controls. Spouses of patients had higher levels of triglycerides (0.23 mmol/1 (SEM, 0.11), P < 0.05). Our findings add to the growing evidence that predictors for atherosclerotic disease can be detected relatively early in life. It is concluded that reduced levels of HDL3 cholesterol and apolipoprotein A2 may be early risk indicators for coronary atherosclerosis later in life.
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Efficacy of fetal echocardiography and yield by risk category.
OBJECTIVE: To determine the efficacy and yield of tertiary center fetal echocardiography for different high-risk groups. METHODS: Between January 1, 1982, and January 1, 1994, scans for anomalies were performed on 3246 women at increased risk for congenital heart disease in their offspring. Gestational age was 16-25 weeks in 83%. Maternal and gestational age as well as prenatal and postnatal diagnosis were recorded, and follow-up was sought for all pregnancies. By comparing prenatal and postnatal diagnoses, sensitivity, specificity, and predictive values were estimated. Multiple logistic regression was applied to establish the relative yield within the high-risk group. RESULTS: Follow-up was available in 3223 cases (99%). In a separate validation study of 777 women for whom a second set of follow-up data was requested, no additional anomalies were revealed. In total, 20 of 47 cases of cardiac malformations were detected (sensitivity 43%). When taking into account cases that remained undetected because of unfavorable scanning conditions (ie, minute size of the anomaly, awkward fetal position, or severe maternal obesity), the sensitivity for congenital heart disease rose to 51%. Specificity and predictive values were high (above 95%). The relative yield across the high-risk group appeared to be high for parental congenital heart disease and maternal diabetes mellitus, whereas a previous infant or other relatives affected, maternal anti-epileptic drug use, maternal drug abuse, and other reasons for referral each had an estimated yield approximately equal to the prevalence of congenital heart disease in the general population (0.8%). CONCLUSION: Fetal echocardiography for known increased risk appears to be moderately effective. Clear differences in yield are present across currently accepted risk categories.
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Common carotid intima-media thickness as an indicator of atherosclerosis at other sites of the carotid artery. The Rotterdam Study.
To evaluate the association between common carotid intima-media thickness and noninvasively assessed atherosclerosis elsewhere in the carotid artery, we used data from the Rotterdam Study, a single-center population-based, prospective follow-up study among 7983 subjects aged 55 years or older. Baseline measurements included ultrasonographic evaluation of the vessel wall characteristics of the carotid arteries, that is, assessment of the presence of atherosclerotic lesions, measurement of common carotid intima-media thickness, and determination of the presence of hemodynamically significant stenosis. The present analysis is based on data obtained from the first 1000 participants. The results were adjusted for age and gender. An increase of 1 standard deviation in common carotid intima-media thickness (0.19 mm) doubled the risk of plaques in the carotid bifurcation: odds ratio 2.0 (95% confidence interval (CI): 1.6, 2.4). For hemodynamically significant stenosis of the right internal carotid artery (> or = 50%), a 1.4 (95% CI: 1.0, 2.0) increased risk was found. The risk of atherosclerotic plaques in the bifurcation in subjects with an intima-media thickness above 0.89 mm (upper quintile) relative to those with an intima-media thickness below 0.63 mm (lowest quintile) was 6.0 (95% CI: 3.5, 10.2). For internal carotid artery stenosis, a relative risk of 2.8 (95% CI 0.5, 15.7) was found. The findings of the present study provide evidence that increased common carotid intima-media thickness indicates atherosclerosis at other sites of the carotid artery. This study lends support to the view that noninvasively assessed increased intima-media thickness of the distal common carotid artery is an indicator of generalized atherosclerosis.
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Hyperinsulinemia and bone mineral density in an elderly population: The Rotterdam Study.
We studied the association between insulin and glucose levels and bone mineral density (BMD) in a population based study of 5931 elderly men and women. Serum insulin was measured 2 h after a nonfasting oral glucose load in subjects not using antidiabetes medication. BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine and the proximal femur. In addition, the participants were asked about fractures in the preceding 5 years. Higher bone mass was associated with higher glucose and postload insulin levels at all sites, as well as with increased waist/hip ratio and body mass index. In men, the mean age-adjusted BMD at the lumbar spine (in mg/cm2) increased 4.64 per mmol/L serum glucose (95% CI 1.46-7.82) and 0.35 per mU/L postload insulin (0.17-0.53). In women, these values were 6.88 (4.37-9.39) for glucose and 0.25 (0.11-0.39) for insulin (for all analyses: p < 0.01). The relations were essentially the same with BMD measured in the femur, as well as after adjustment for waist/hip ratio. After adjustment for body mass index, the associations were reduced and lost statistical significance in women. After excluding subjects with diabetes mellitus, the results remained the same. Subjects with a history of nonvertebral fractures had a lower BMD and lower postload insulin levels than those without. The difference in insulin levels was statistically significant in men only (12.5 mU/L, p < 0.001). Excluding men with diabetes mellitus or further adjustment for waist/hip ratio, body mass index or BMD did not change this difference. These results suggest that increased insulin levels are associated with an increased BMD and might be related to a lower fracture rate.
Absorptiometry, Photon↗
Primary open-angle glaucoma, intraocular pressure, and diabetes mellitus in the general elderly population. The Rotterdam Study.
PURPOSE: To investigate the association of primary open-angle glaucoma and intraocular pressure (IOP) with newly diagnosed diabetes mellitus. METHODS: Subjects participating in the Rotterdam Study (n = 4178; ages, 55 years and older) were examined according to standard protocols, including a medical history interview, perimetry, applanation tonometry, funduscopy, and a nonfasting glucose tolerance test. Glaucoma was defined by the presence of a glaucomatous visual field defect. A distinction was made between high-tension glaucoma and normal-tension glaucoma. The relation of glaucoma and IOP with newly diagnosed diabetes mellitus and blood glucose was analyzed using regression analysis. RESULTS: The presence of diabetes mellitus was associated with an overall rise in mean IOP of both eyes of 0.31 mmHg (95% confidence interval, 0.12-0.50), and with a threefold increased presence of high-tension glaucoma (odds ratio, 3.11; 95% confidence interval, 1.12-8.66). A 10-mmol/l higher random serum glucose level was borderline significantly associated with a mean IOP that was, on average, 0.41 mmHg (95% confidence interval, -0.02-0.84) higher and with an odds ratio of 2.82 (95% confidence interval, 0.92-8.58) for high-tension glaucoma. A 10-mmol/l rise in serum glucose on a glucose tolerance test was associated with an overall rise of mean IOP of 0.59 mmHg (95% confidence interval, 0.26-0.92) and with an odds ratio of 1.88 (95% confidence interval, 0.81-4.32) for high-tension glaucoma. CONCLUSION: Newly diagnosed diabetes mellitus and high levels of blood glucose are associated with elevated IOP and high-tension glaucoma.
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Increasing incidence of aneurysms of the abdominal aorta in The Netherlands.
OBJECTIVES: To study the trend in incidence of aneurysms of the abdominal aorta in The Netherlands during the past two decades. SETTING: The Dutch population from 1972 to 1992. DESIGN: Analysis of all hospital admissions and deaths due to aneurysms of the abdominal aorta. OUTCOME MEASURES: Age adjusted and age specific mortality and discharge rates. In-hospital mortality after surgery upon aneurysms of the abdominal aorta. RESULTS: From 1972 to 1992 age adjusted mortality from aneurysms of the abdominal aorta rose from 3.1 to 8.1 per 100,000 in men, and from 1.4 to 2.2 in women. Age adjusted discharge rates (alive and dead) for non-ruptured abdominal aortic aneurysms increased from 3.7 to 37.6 per 100,000 in men and from 1.2 to 5.5 in women. For ruptured aneurysms, the age adjusted discharge rates increased from 2.4 to 10.3 per 100,000 in men and from 0.7 to 1.7 in women. Age adjusted in-hospital mortality after surgery upon non-ruptured aneurysms was halved from 13% in 1972 to 7% in 1992, mortality after acute repair upon ruptured aneurysms also decreased from 52% in 1972 to 36% in 1992. CONCLUSIONS: There was an impressive increase in the hospital based incidence for aneurysms of the abdominal aorta during the past two decades in The Netherlands. An improved detection rate through ultrasound is probably a major contributor to this increase, but gender differences and the rise in the number of ruptured aneurysms suggest that a real increase in incidence may exist, especially in men. Surgical outcome for both ruptured and non-ruptured aneurysms of the abdominal aorta improved.
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The association of abnormalities on physical examination of the hip and knee with locomotor disability in the Rotterdam Study.
To assess the influence of abnormalities found on physical examination of the hips and knees on disability 1156 men and 1739 women aged > or = 55 yr (the Rotterdam Study) were asked about locomotor disability (LD) using six questions of the Health Assessment Questionnaire (HAQ). The prevalence of LD was 20.2% for men and 31.9% for women. Moderately restricted range of motion of the hips and knees occurred in 34.5% of the men and 38.6% of the women. The prevalence of instability of the knees was 12.5% for men and 16.8% for women. Varus deformity in men (10.1%) and valgus deformity in women (15.0%) were the most common deformities of the knees. Restricted flexion of the hips was the strongest determinant of LD. Age-adjusted odds ratios for restricted hip flexion of LD were 4.7% (95% CI: 3.2-6.8) for men and 3.5 (2.7-4.5) for women. Valgus deformity, knee instability and obliquity were risk factors only in women. Adjustment of these odds ratios for morning stiffness and joint pain did not alter the estimates.
Activities of Daily Living↗
Insulin, hypertension and antihypertensive drugs in elderly patients: the Rotterdam Study.
OBJECTIVE: To investigate the association between insulin, hypertension and antihypertensive drug use in elderly patients. DESIGN AND METHODS: Blood pressure, use of antihypertensive drugs and glucose metabolism were examined in 5453 men and women (mean age 68.8 years). This was part of the baseline examination of the Rotterdam Study, a population-based study of chronic diseases in elderly patients. Serum insulin was measured 2 h after an oral glucose load. RESULTS: Patients with hypertension had a significantly higher mean post-load insulin level than those without: 71.3 mU/l versus 59.3 mU/l (P < 0.001, adjusted for age). Systolic blood pressure increased by 0.25 mmHg per 10 mU/l insulin (95% confidence interval 0.15-0.35, adjusted for age, sex and antihypertensive drugs), whereas the increase in diastolic blood was 0.07 mmHg per 10 mU/l (0.01-0.13). Whereas insulin resistance was higher in patients with hypertension, the increase in insulin resistance with age was much more apparent in normotensive patients, resulting in similar insulin levels at high ages. Those using antihypertensive drugs, however, had higher insulin levels at all ages. CONCLUSION: The results of this study show that hyperinsulinemia is associated with raised blood pressure in elderly people, and suggest that the age-associated increase in insulin resistance is diminished in patients with raised blood pressure. The use of antihypertensive drugs, however, appears to be accompanied by an independent additional increase in insulin resistance at all ages.
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Dietary electrolyte intake and blood pressure in older subjects: the Rotterdam Study.
OBJECTIVE: To examine the relation between dietary electrolyte intake and blood pressure in older people. METHODS: The study included 3239 participants of the Rotterdam Study (41% of the total cohort) who were aged over 55 years and had not been prescribed antihypertensive drugs. Their dietary intake was assessed by a semiquantitative food frequency questionnaire. The association of energy-adjusted intakes of potassium, magnesium and calcium with blood pressure was studied in a linear regression model with adjustment for age, sex, body mass index and alcohol intake. RESULTS: An increase in potassium intake of 1 g/day was associated with a 0.9 mmHg lower systolic and a 0.8 mmHg lower diastolic blood pressure. An increase in magnesium intake of 100 mg was associated with a 1.2 mmHg lower systolic and a 1.1 mmHg lower diastolic blood pressure. Calcium intake was not independently related to blood pressure, except for a subgroup of 1360 hypertensive subjects in which a significant inverse association with diastolic blood pressure was observed. CONCLUSIONS: Our findings support the view that an increase in the intake of foods rich in potassium and magnesium could lower blood pressure at older age.
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Serum lipids in early pregnancy and risk of pre-eclampsia.
OBJECTIVE: To determine whether first and late second trimester serum total and high density lipoprotein cholesterol are associated with blood pressure, uterine artery pulsatility index and pregnancy outcome. DESIGN: A prospective cohort study. Data were analysed using multiple linear and logistic regression analysis. PARTICIPANTS: Three hundred and ninety-three pregnant women requesting chorionic villus sampling because of advanced maternal age (36 years and older). MAIN OUTCOME MEASURES: Serum total cholesterol and high density lipoprotein cholesterol were measured by an automated enzymatic method. Uterine artery flow velocity waveforms were recorded using continuous Doppler ultrasound. Pregnancy outcome was assessed by questionnaire. RESULTS: First trimester serum total cholesterol was significantly associated with the risk of pre-eclampsia, with the adjusted relative risk exceeding 5 for women with serum total cholesterol levels above 6.0 mmol/1 when compared with women with a cholesterol level below 5.0 mmol/1. First trimester serum total cholesterol also showed a significant relationship with diastolic blood pressure (coefficient of linear regression = 0.02 (mmol/1)/mm Hg, 95% CI = 0.01 to 0.03), and the change in both diastolic and systolic blood pressure from the first to the late second trimester was associated with linear changes in serum total cholesterol and high density lipoprotein cholesterol. CONCLUSIONS: These data suggest a relation between serum lipids in early pregnancy and the development of pre-eclampsia.
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