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Ian A Greer

Publications and source records attributed to Ian A Greer.

At least 37 records · Page 2Linked to original sources
PubMed2004

Pre-eclampsia and cardiovascular disease: metabolic syndrome of pregnancy?

Complications of pregnancy, particularly pre-eclampsia (PET) and intra-uterine growth restriction (IUGR) have been associated with future maternal cardiovascular disease (CVD). Pre-eclampsia, characterised by insulin resistance, widespread endothelial damage and dysfunction, coagulation defects and increased systemic inflammatory response, shares many risk factors with CVD. This review describes the pathology of PET and the maternal metabolic response and discusses the possible underlying mechanisms common to CVD and PET. The contributions of pre-existing risk factors and of the exaggerated atherogenic-like response seen in PET persisting post-partum to future CVD are considered. The potential for interventions based on early assessment of cardiovascular risk is addressed. We conclude that despite the low immediate cardiovascular risk in a population of young women, a pregnancy with multiple complications including PET, premature delivery and IUGR, carries a seven-fold additive risk of future disease. These women may be an appropriate cohort for CVD risk screening and for possible intervention.

Cardiovascular Diseases↗
PubMed2004

Divergent metabolic and vascular phenotypes in pre-eclampsia and intrauterine growth restriction: relevance of adiposity.

OBJECTIVE: Pre-eclampsia (PE) and intrauterine growth restriction (IUGR) may both arise secondary to inadequate trophoblast invasion. Maternal vascular disease is evident only in PE. Little mechanistic evidence exists to explain this dichotomy. METHODS: We employed laser Doppler imaging (LDI) to examine microvascular function in 15 women with PE and 30 healthy pregnant women matched for body mass index (BMI). We also examined 16 women with IUGR. Other factors examined included indices of inflammation, lipoproteins, leptin and insulin concentrations. RESULTS: Women with PE had double the concentration of leptin and 30% higher triglyceride than controls. Vascular cell adhesion molecule (VCAM)-1 and interleukin (IL)-6 were also higher in women with PE, with both factors correlating with leptin independently of BMI. No difference in microvascular reactivity was observed between controls and women with PE. Women with IUGR had a four-unit smaller BMI than women with PE. When compared with controls, they also had lower low-density lipoprotein cholesterol (LDL-C) concentrations and systemic inflammatory measures were not elevated. CONCLUSIONS: The technique of LDI is not sensitive to the vascular dysfunction of PE. However, circulating endothelial-derived factors are elevated in association with markedly elevated leptin levels. Therefore, women with IUGR may demonstrate a protective role for their 'leanness' with regard to maternal systemic inflammatory effect.

Adipose Tissue↗
PubMed2004

The impact of guidelines on mild hypertension in pregnancy: time series analysis.

OBJECTIVE: To determine the impact of a national strategy to promote implementation of a guideline on the management of mild, non-proteinuric hypertension in pregnancy. DESIGN: Simple, interrupted time series analysis. SETTING: Four maternity units in Scotland. POPULATION: Women delivering a live or stillborn baby. METHODS: Dissemination of the guideline under the auspices of a national clinical effectiveness programme, supported by a national launch meeting and feedback from a survey of obstetricians highlighting aspects of care that could be improved. MAIN OUTCOME MEASURES: Appropriateness of initial investigation and subsequent clinical management, and costs of guideline development and implementation activities. DATA COLLECTION: Twenty-four months pre-intervention and 12 months post-intervention data were abstracted from a random sample of case notes. RESULTS: Initial investigation was consistent with recommendations for 59.9% out of 1263 women and subsequent clinical management for 67.6% out of 1081 in whom a diagnosis could be made from available data. There were no significant changes in the appropriateness of initial investigation (10.6%; 95% confidence interval [CI] -0.1% to 19.3%; decreasing by 1.2% per month post-implementation, 95% CI -2.5% to 0.1%) or clinical management (-0.3%; 95% CI -8.7% to 11.2%). Guideline development and implementation cost an estimated pound 2784 per maternity unit in Scotland. CONCLUSIONS: Clinical care of mild hypertension in pregnancy remains highly inconsistent. The lack of the intervention effect may be related to the complexity of the guideline recommendations and the nature of the implementation strategy.

Adult↗
PubMed2004

Use of antithrombotic agents during pregnancy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

This chapter about the use of antithrombotic agents during pregnancy is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following: for women requiring long-term vitamin K antagonist therapy who are attempting pregnancy, we suggest performing frequent pregnancy tests and substituting unfractionated heparin (UFH) or low molecular weight heparin (LMWH) for warfarin when pregnancy is achieved (Grade 2C). In women with acute venous thromboembolism (VTE), we recommend adjusted-dose LMWH throughout pregnancy or IV UFH for at least 5 days, followed by adjusted-dose UFH or LMWH for the remainder of the pregnancy and at least 6 weeks postpartum (Grade 1C+). In patients with a single episode of VTE associated with a transient risk factor that is no longer present, we recommend antepartum clinical surveillance and postpartum anticoagulants (Grade 1C). In patients with a single episode of VTE and thrombophilia or strong family history of thrombosis and not receiving long-term anticoagulants, we suggest antepartum prophylactic or intermediate-dose LMWH or minidose or moderate-dose UFH, plus postpartum anticoagulants (Grade 2C). In patients with multiple (two or more) episodes of VTE and/or women receiving long-term anticoagulants, we suggest antepartum adjusted-dose UFH or adjusted-dose LMWH followed by long-term anticoagulants postpartum (Grade 2C). For pregnant patients with antiphospholipid antibodies (APLAs) and a history of two or more early pregnancy losses or one or more late pregnancy losses, preeclampsia, intrauterine growth retardation, or abruption, we suggest antepartum aspirin plus minidose or moderate-dose UFH or prophylactic LMWH (Grade 2B). We suggest one of the following approaches for women with APLAs without prior VTE or pregnancy loss: surveillance, minidose heparin, prophylactic LMWH, and/or low-dose aspirin, 75 to 325 mg/d (all Grade 2C). In women with prosthetic heart valves, we recommend adjusted-dose bid LMWH throughout pregnancy (Grade 1C), aggressive adjusted-dose UFH throughout pregnancy (Grade 1C), or UFH or LMWH until the thirteenth week and then change to warfarin until the middle of the third trimester before restarting UFH or LMWH (Grade 1C). In high-risk women with prosthetic heart valves, we suggest the addition of low-dose aspirin, 75 to 162 mg/d (Grade 2C).

Contraindications↗
PubMed2003

Paradoxical elevation in adiponectin concentrations in women with preeclampsia.

Adiponectin is a recently identified, insulin-sensitizing and anti-inflammatory protein released by adipocytes, which is paradoxically reduced in obesity. It suppresses endothelial activation. Physiological insulin resistance occurs in normal pregnancy and is exaggerated in women with preeclampsia (PE), together with enhanced inflammatory and endothelial activation. Women with increased body mass index (BMI) and insulin resistance are predisposed to PE. We hypothesized that adiponectin concentrations are reduced in normal pregnancy compared with postpartum values and further reduced in women with PE. Fifteen women with PE and 30 control subjects with similar first trimester BMI had adiponectin concentrations measured in the third trimester; postpartum measurements were repeated in 16 control subjects. Adiponectin concentration in healthy pregnant women correlated inversely with early pregnancy BMI (r=-0.47, P=0.01) and fasting insulin concentrations (r=-0.58, P=0.001). However, adiponectin concentrations did not differ significantly in pregnancy and postpartum samples (mean change, -0.15 microg/mL; 95% CI, -2.28 to 1.98, P=0.88). Plasma adiponectin concentrations were markedly elevated (P=0.01) in women with PE (mean, 21.6; SD, 8.18 microg/mL) compared with control subjects (mean, 14.7; SD, 7.06 microg/mL). Moreover, in PE, adiponectin concentrations did not correlate with first trimester BMI or insulin or with serum urate or creatinine concentrations or urinary protein levels. We conclude that plasma adiponectin concentrations are not elevated in normal human pregnancy and paradoxically elevated (by 47%) in women with PE. This may be secondary to exaggerated nonspecific adipocyte lipolysis or as a physiological response to enhance fat utilization and attenuate endothelial damage. Future studies should determine whether adiponectin concentrations help improve prediction of PE.

Adiponectin↗
PubMed2003

Classic and novel risk factor parameters in women with a history of preeclampsia.

Epidemiological studies demonstrate a relation between preeclampsia (PE) and an increased risk of maternal coronary heart disease (CHD) in later life. However, there are few data available to explain any underlying mechanism. We recruited 40 primigravid women with a history of proteinuric PE delivering between 1975 and 1985 and 40 controls, matched as a group for time of index pregnancy, smoking, and current body mass index to assess classic (lipids, blood pressure) and novel (adhesion molecules, insulin, leptin) risk factor pathways. Women with a history of PE had higher diastolic blood pressure compared with controls (83 vs 76 mm Hg, P<0.05), but there were no significant differences in fasting lipoprotein concentrations (P>0.20). However, concentrations of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 (ICAM-1) in particular were higher in the PE group by 14% (P=0.038) and 44% (P=0.002), respectively. The cases also demonstrated a tendency toward higher fasting insulin (P=0.08) concentrations and had higher glycosylated hemoglobin levels (P=0.004). Leptin concentrations were not significantly elevated. Interestingly, significantly more of the women with history of PE were classified as menopausal (37.55% vs 17.5%, P=0.045). The differences in ICAM-1 concentration persisted (P=0.010) after adjustment for potential confounders, including hormonal use/menopausal status, antihypertensive or lipid-lowering therapy, and social class. We conclude that classic risk factors alone cannot fully explain the elevated CHD risk in women with a history of PE. Rather markedly elevated ICAM-1 concentrations and specific but subtle features of the metabolic syndrome (glucose, blood pressure) are likely to be involved.

Adult↗
PubMed2003

Thrombophilia: implications for pregnancy outcome.

There is growing evidence implicating congenital and acquired thrombophilias in the pathophysiological processes underlying miscarriage, intrauterine growth restriction (IUGR) and pre-eclampsia. Pregnancy itself is notably a hypercoagulable state, at least in part, due to the physiological changes in the coagulation and fibrinolytic systems; this has the potential for interaction with an acquired or heritable thrombophilia to cause adverse experiences. Recurrent fetal loss is associated with antiphospholipid antibody syndrome, procoagulant platelet microparticles and some inherited thrombophilias such as Factor V Leiden. There have been reports of both heritable and acquired thrombophilias being associated with pre-eclampsia, IUGR and abruption. However, these associations are not consistently reported with hereditary thrombophilias. The presence of thrombophilia might influence the severity of a condition such as pre-eclampsia, rather than cause it. The risk of fetal loss related to antiphospholipid syndrome can be reduced with antithrombotic therapy with heparin and low dose aspirin. Whether this extends to other thrombophilic conditions associated with adverse pregnancy outcome is not clear and further investigation is required. Screening for, and finding a, thrombophilic disease in patients with problems such as recurrent miscarriage, intrauterine death, intrauterine growth restriction and pre-eclampsia, may reflect an increased risk of venous thromboembolism (VTE).

Abortion, Spontaneous↗
PubMed2003

Prevention and management of venous thromboembolism in pregnancy.

Pulmonary thromboembolism is a major cause of maternal mortality. DVT causes significant morbidity in pregnancy and in later life owing to the post-thrombotic syndrome. Obstetricians must have an understanding of the risk factors for VTE, the appropriate use of prophylaxis, the need for objective diagnosis in women with suspected VTE, and the appropriate use of anticoagulant therapy. Greater use of prophylaxis is needed after vaginal delivery. Because acute VTE is relatively uncommon, greater use of proposed guidelines [24,84,85] may be of value in improving management, but the involvement of clinicians with expertise in the management of these cases is also important.

Female↗
PubMed2003

Prevention of venous thromboembolism in pregnancy.

Pulmonary thromboembolism, rising from deep venous thrombosis (DVT), is a major cause of maternal death in the developed World. DVT is a significant source of morbidity in pregnancy and the puerperium with long-term sequelae such as post-thrombotic syndrome. The major risk factors for venous thromboembolism (VTE) are: increasing age, particularly over 35 years; operative vaginal delivery; Caesarean section, especially emergency Caesarean section in labour; high body mass index; previous VTE, especially if idiopathic or thrombophilia-associated; thrombophilia; and a family history of thrombosis suggestive of an underlying thrombophilia. Thromboprophylaxis centres largely on the use of low-molecular-weight heparin (LMWH). LMWHs, such as enoxaparin and dalteparin, have substantial clinical and practical advantages compared with unfractionated heparin, particularly in terms of improved safety with a significantly lower incidence of heparin-induced osteoporosis and thrombocytopenia. Such agents should be used in women with significant risk factors for VTE both antenatally and post-partum.

Female↗
PubMed2003

Inherited thrombophilia and venous thromboembolism.

Pulmonary thromboembolism (PTE) is the major cause of maternal death in the UK. Underlying PTE is the problem of deep venous thrombosis (DVT). Inherited thrombophilia will be found in about 50% of women with a personal history of venous thromboembolism (VTE), and screening for thrombophilia should be considered in women with a personal or family history of VTE. There is currently no place for universal screening for thrombophilia in pregnancy. There are particular considerations with regard to the management of thrombophilia in pregnancy. Low-molecular-weight heparins are now the heparin of choice in pregnancy because of a better side-effect profile (substantially reduced risk of heparin-induced osteoporosis and heparin-induced thrombocytopaenia) compared to unfractionated heparin, good safety record for mother and fetus and convenient once-daily dosing for prophylaxis.

Anticoagulants↗
PubMed2003

Metabolic, inflammatory and haemostatic effects of a low-dose continuous combined HRT in women with type 2 diabetes: potentially safer with respect to vascular risk?

BACKGROUND: Conventional hormone replacement therapy (HRT) containing conjugated equine oestrogen (CEE) and medroxyprogesterone acetate (MPA) increases triglyceride, C-reactive protein (CRP) and coagulation Factor VII concentrations, potentially explaining their increased coronary heart disease (CHD) and stroke risk. OBJECTIVE: To assess the metabolic effects of a continuous combined HRT containing 1 mg oestradiol and 0.5 mg norethisterone or matching placebo. DESIGN: Double-blind, randomized placebo-controlled trial. PATIENTS: Fifty women with type 2 diabetes. MEASUREMENTS: Classical and novel risk factors for vascular disease. RESULTS: Triglyceride concentration was not altered (P = 0.31, change in active arm relative to placebo) and low-density lipoprotein (LDL) cholesterol concentration declined 13% (P = 0.018). IL-6 concentration (mean difference -1.42 pg/ml, 95% CI: -2-55 to -0-29 IU/dl, P = 0.015), Factor VII (-32 IU/dl, -43 to -21 IU/l, P < 0.001) and tissue plasminogen activator antigen (by 13%, P = 0.005) concentrations fell, but CRP was not significantly altered (P = 0.62). Fasting glucose (P = 0.026) also declined significantly, but there are no significant effects on HBA1c, Factor IX or APC resistance. CONCLUSIONS: HRT containing 1 mg oestradiol and 0.5 mg norethisterone may avoid the adverse metabolic effects potentially implicated in the elevated CHD and stroke risk induced by conventional higher dose HRT. This type of preparation may therefore be more suitable than conventional HRT for women at elevated CHD risk such as those with type 2 diabetes. Large randomized controlled trials of such low dose preparations, powered for cardiovascular end points, are now needed.

Autoantigens↗
PubMed2003

Prevention and treatment of arterial thrombosis in pregnancy.

In the last few years there has been a marked increase in the recognition of patients who are potentially at risk of arterial occlusive events during pregnancy. This includes patients with a previous history of arterial occlusion such as myocardial infarction and stroke, patients known to carry acquired or inherited thrombotic risk factors including sickle cell and myeloproliferative disorders, and patients with prosthetic heart valves. This review details the management options for prevention of arterial occlusions in these at-risk patients and outlines potential management strategies for arterial occlusions occurring during pregnancy.

Arterial Occlusive Diseases↗
PubMed2003

Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term.

Accumulating evidence suggests that human parturition represents an inflammatory process. Leukocytes are known to infiltrate uterine tissues but the exact timing, nature and quantity of these cells has not been formally characterized. We have previously demonstrated an apparent increase in pro-inflammatory cytokines within tissues of the labouring uterus. The aims of this study were to quantify and compare the leukocyte subpopulations before and during labour in fetal membranes, decidua and cervix and to quantify and compare mRNA expression of interleukin-1beta (IL-1beta), IL-6, IL-8 and tumour necrosis factor-alpha in myometrium, cervix, chorio-decidua and amnion. Biopsies of each of these tissues were obtained from pregnant women delivered by Caesarean section before and after the onset of spontaneous labour at term. Subpopulations of leukocytes were identified using immunohistochemistry and cytokine mRNA expression was quantified using Northern analysis. We found that parturition was associated with a significant increase in IL-1beta, IL-6 and IL-8 mRNA expression in cervix and myometrium, IL-6 and IL-8 mRNA expression in chorio-decidua and IL-1beta and IL-8 mRNA expression in amnion. Histological analysis demonstrated that leukocytes (predominantly neutrophils and macrophages) infiltrate the uterine cervix coincident with the onset of labour. These data lend further support to the hypothesis that labour is an inflammatory process.

Amnion↗
PubMed2003

The G-to-T point mutation in codon 34 of the factor XIII gene and the risk of pre-eclampsia.

A G-to-T point mutation in exon 2 of the FXIII A-subunit gene results in a leucine rather than valine at amino acid position 34 of the factor XIII molecule. The presence of leucine has been associated with a reduced risk of both arterial and venous thrombosis. We examined the prevalence of this point mutation in 102 cases of pre-eclampsia and 208 matched control subjects, as inherited and acquired risk factors for arterial and venous thrombosis are associated with an increased risk of pre-eclampsia. The GT genotype was observed in 38% of controls and 29.4% of cases and the TT genotype was observed in 6.7% of controls and 5.9% of cases. In subjects heterozygous for the T genotype (GT) the relative risk of pre-eclampsia was 0.7 [95% confidence interval (CI95 ) 0.4-1.1] when compared with the GG genotype. For subjects homozygous for the T allele the relative risk for pre-eclampsia was 0.8 (CI95 0.3-2.1) when compared with the GG genotype. The risk associated with the T allele in the heterozygous and homozygous forms compared with the GG genotype was 0.7 (CI95 0.4-1.1). We conclude that the presence of leucine at this site is not associated with a protection against pre-eclampsia to the magnitude of that reported in other thrombotic disease.

Adult↗
PubMed2003

Enhancement of endothelial function by pregnancy: inadequate response in women with type 1 diabetes.

OBJECTIVE: Pregnant women with type 1 diabetes have a substantially increased risk of vascular complications. Our aim was to study vascular function and metabolic and inflammatory risk factors during the antenatal and postpartum periods in women with type 1 diabetes compared with healthy control subjects. RESEARCH DESIGN AND METHODS: A total of 15 women with diabetes and 30 control subjects were recruited in the third trimester of pregnancy. Of these women, 9 case subjects and 16 control subjects were reinvestigated in the postnatal period. Blood samples were collected and microvascular skin perfusion was assessed in vivo using laser Doppler imaging and iontophoretic administration of endothelial-dependent (acetylcholine [ACH]) and endothelial-independent (sodium nitroprusside [SNP]) vasodilators. RESULTS: Microvascular responses in both control subjects (ACH, P = 0.018; SNP, P = 0.01) and diabetic women (ACH, P = 0.029; SNP, P = 0.105) were better during pregnancy than in the postnatal period, although responses in women with diabetes were significantly inferior to those in control subjects during both periods (all P < 0.001, two-way ANOVA). This dysfunction existed despite similar lipoprotein profiles. The difference in vascular responsivity between case and control subjects was significantly attenuated by adjustment for differences in HbA(1c) but not C-reactive protein concentrations in the two groups. CONCLUSIONS: Pregnancy enhances microvascular function, but in women with diabetes, such improvements are insufficient to attain responses seen in healthy nonpregnant women. This suggests a persistent vascular defect in young women with type 1 diabetes that may contribute to adverse pregnancy outcome. Our data suggest a role for the chronic effects of hyperglycemia in the impaired vascular responsiveness in such women.

Acetylcholine↗
PubMed2003

Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated by thrombin in human monocytes and THP-1 cells in vitro and in pregnant subjects in vivo.

Monocytes play a pivotal role in both the inflammatory and coagulation responses, which may be mediated through a variety of adhesion molecules on the cell surface, including intercellular adhesion molecule-1 (ICAM-1). Monocytes also possess thrombin receptors. In the current study, we have demonstrated that thrombin can upregulate ICAM-1 mRNA and induce ICAM-1 expression on the monocyte in vitro and that, in vivo, higher monocyte ICAM-1 expression is observed in pregnancy (which is characterised by a physiological increase in thrombin generation). In pregnant subjects, a positive correlation between monocyte ICAM-1 expression and a number of markers of vascular/thrombotic disease (including blood group, acquired activated protein C resistance and non-fasting plasma triglyceride levels) was observed. We also observed a significant relationship between monocyte ICAM-1 expression and soluble plasma ICAM-1 levels, which would be consistent with a contribution of monocytic ICAM-1 to the levels of free ICAM-1 observed in plasma during pregnancy. Consistent with a role in fibrinogen binding, our preliminary in vivo results suggest that monocyte ICAM-1 expression may be a useful marker of the thrombotic/inflammatory response, although further work is required to assess the relationship of monocyte ICAM-1 expression in thrombotic disorders.

Adult↗
PubMed2003

Microvascular dysfunction: a link between pre-eclampsia and maternal coronary heart disease.

Epidemiological studies have recently demonstrated a relationship between pre-eclampsia and coronary heart disease. Insulin resistance has been implicated as a common factor. We have demonstrated, for the first time, using laser Doppler imaging in vivo, impaired microvascular function in women 15-25 years following a pregnancy complicated by pre-eclampsia. Thus, microvascular dysfunction, which is associated with insulin resistance, may be a predisposing vascular mechanism for both coronary heart disease and pre-eclampsia. Pregnancies complicated by pre-eclampsia may identify women at risk of vascular disease in later life and may provide the opportunity for lifestyle and risk factor modification to alter maternal vascular disease risk.

Adult↗