Publications
368 results found
Chambers JC, Kooner JS, 2002, Diabetes, insulin resistance and vascular disease among Indian Asians and Europeans., Semin Vasc Med, Vol: 2, Pages: 199-214, ISSN: 1528-9648
Indian Asians account for one-fifth of all cardiovascular deaths worldwide. Cardiovascular mortality in Indian Asians overseas is higher than in indigenous populations. Diabetes, insulin resistance, and related metabolic disturbances are more common among Indian Asians than Europeans and may account for up to 70% of major Q wave ECG abnormalities in Asians. Previous studies provide evidence that genetic and environmental factors, the latter including intrauterine growth retardation, reduced physical activity, increased weight, and dietary intake, contribute to the high prevalence of diabetes and insulin resistance in Asians. The importance of conventional coronary risk factors is emphasized by studies showing higher prevalence of cigarette smoking, hypertension, and hypercholesterolemia in migrant and urban Indians compared with rural Indians. Recent studies suggest that new risk factors, including C-reactive protein, homocysteine, and lipoprotein(a), are increased among Indian Asians compared with Europeans and may contribute to part of the excess cardiovascular risk in Asians. Further work is needed to identify the precise genetic and environmental mechanisms underlying increased vascular risk in Indian Asians. Clinical strategies must be developed that identify Indian Asians at increased risk and assess the effectiveness of treatment for insulin resistance, and other cardiovascular risk factors, in this racial group.
Chambers JC, 2002, Homocysteine: a reversible risk factor for coronary heart disease, EMBODY 2000 Conference, Publisher: CAMBRIDGE UNIV PRESS, Pages: 374-378
Chambers JC, Ahmed N, McGregor A, et al., 2001, Influenza vaccination induces vascular endothelial dysfunction in human subjects, CIRCULATION, Vol: 104, Pages: 561-561, ISSN: 0009-7322
Chambers JC, Kooner JS, 2001, Homocysteine: a novel risk factor for coronary heart disease in UK Indian Asians, HEART, Vol: 86, Pages: 121-122, ISSN: 1355-6037
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- Citations: 27
Chambers JC, Ueland PM, Wright M, et al., 2001, Investigation of relationship between reduced, oxidized, and protein-bound homocysteine and vascular endothelial function in healthy human subjects., Circ Res, Vol: 89, Pages: 187-192
Previous studies investigating homocysteine and vascular disease have relied on total plasma homocysteine as the sole index of homocysteine status. We examined the dynamic relationship between vascular endothelial function and concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine to identify the homocysteine form associated with endothelial dysfunction in humans. We investigated 14 healthy volunteers (10 men, 4 women). Brachial artery flow-mediated dilatation was measured at baseline and at 30, 60, 120, 240, and 360 minutes after oral (1) L-methionine (50 mg/kg), (2) L-homocysteine (5 mg/kg), and (3) placebo. Plasma concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine were measured at each time point, and nitroglycerin-induced dilatation at was assessed at 0, 120, and 360 minutes. Flow-mediated dilatation fell, and concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine increased after oral homocysteine and oral methionine (all P<0.05 for difference in time course compared with placebo). Flow-mediated dilatation showed a reciprocal relationship with reduced homocysteine during both homocysteine and methionine loading. In both loading studies, peak reduction in flow-mediated dilatation coincided with maximal reduced homocysteine concentrations. In contrast, there was no consistent relationship between flow-mediated dilatation and free oxidized homocysteine, protein-bound oxidized homocysteine, or related species. Nitroglycerin-induced dilatation was unchanged by oral homocysteine and oral methionine (P>0.10 compared with placebo). Reduced homocysteine is closely associated with endothelial dysfunction during oral methionine and oral homocysteine loading. Our observations support the hypothesis that reduced homocysteine is the deleterious form of homocysteine for vascular function in vivo and suggest a less important role for other homocysteine species.
Chambers JC, Ueland PM, Wright M, et al., 2001, Investigation of relationship and protein-bound homocysteine between reduced, oxidized, and vascular endothelial function in healthy human subjects, CIRCULATION RESEARCH, Vol: 89, Pages: 187-192, ISSN: 0009-7330
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- Citations: 81
Chambers JC, Eda S, Bassett P, et al., 2001, C-reactive protein, insulin resistance, central obesity, and coronary heart disease risk in Indian Asians from the United Kingdom compared with European whites, CIRCULATION, Vol: 104, Pages: 145-150, ISSN: 0009-7322
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- Citations: 301
Chambers JC, Kooner JS, 2001, Homocysteine - an innocent bystander in vascular disease?, EUROPEAN HEART JOURNAL, Vol: 22, Pages: 717-719, ISSN: 0195-668X
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- Citations: 8
Chambers JC, Fusi L, Malik IS, et al., 2001, Association of maternal endothelial dysfunction with preeclampsia, JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, Vol: 285, Pages: 1607-1612, ISSN: 0098-7484
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- Citations: 392
Chambers JC, Haskard DO, Kooner JS, 2001, Vascular endothelial function and oxidative stress mechanisms in patients with Behcet's syndrome, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 37, Pages: 517-520, ISSN: 0735-1097
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- Citations: 178
Chambers JC, Seddon MDI, Shah S, et al., 2001, Homocysteine - a novel risk factor for vascular disease, JOURNAL OF THE ROYAL SOCIETY OF MEDICINE, Vol: 94, Pages: 10-13, ISSN: 0141-0768
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- Citations: 30
Chambers JC, Ueland PM, Obeid OA, et al., 2000, Improved vascular endothelial function after oral B vitamins - An effect mediated through reduced concentrations of free plasma homocysteine, CIRCULATION, Vol: 102, Pages: 2479-2483, ISSN: 0009-7322
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- Citations: 199
Chambers JC, Ireland H, Thompson E, et al., 2000, Methylenetetrahydrofolate reductase 677 <i>C</i>→<i>T</i> mutation and coronary heart disease risk in UK Indian Asians, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, Vol: 20, Pages: 2448-2452, ISSN: 1079-5642
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- Citations: 49
Chambers JC, Kooner JS, 2000, Inflammatory mechanisms may contribute to increased coronary heart disease mortality in UK Indian Asians, CIRCULATION, Vol: 102, Pages: 433-433, ISSN: 0009-7322
Brattström L, 2000, Homocysteine and heart disease in Indian Asians., Lancet, Vol: 355, ISSN: 0140-6736
Chambers JC, Wrigley J, Kooner JS, 2000, Evaluation of the Joint British Societies coronary heart disease risk calculator in UK Indian Asians, Heart, Vol: 83, ISSN: 1355-6037
Background: Coronary heart disease (CHD) mortality is 40% higher in UK Indian Asians (IA) than European whites (EW). We have evaluated whether the increased CHD risk in IA is detected by the Joint British Societies (JBS) CHD risk calculator. Methods: We investigated 518 IA and 507 EW men (aged 35-60 yrs) without known CHD, who were recruited from the lists of 57 GPs with a 56% response rate. Coronary risk factors were measured, and risk of CHD mortality determined using the JBS risk calculator. Results: The CHD risk factors of subjects are summarised (table). The calculated 10 year probability of CHD death (mean±SEM) was similar in IA compared to EW, using either systolic BP (1.9±0.2 vs 2.0±0.2 %, P=0.40) or diastolic BP (1.9±0.2 vs 2.0±0.2 %, P=0.53) in the equation. Conclusions: The JBS risk calculator does not detect the increased risk of CHD mortality in IA compared to EW. Our results suggest that this calculator may be misleading, and should be used with caution, in non-white ethnic populations. IA EW P= Age (yrs) 49.3±0.3 49.6±0.3 NS Diabetes (%) 16 4 0.001 Hypertension (%) 37 22 0.001 Smoking (%) 8 29 0.001 Systolic BP (mmHg) 131±1 128±1 0.01 Diastolic BP (mmHg) 83±1 81±1 0.001 Total cholesterol (mmol/L) 5.6±0.1 5.6±0.1 0.001 HDL cholesterol (mmol/L) 1.22±0.02 1.33±0.02 0.001 Triglycerides (mmol/L) 1.8±0.1 1.3±0.1 0.001 Fasting glucose (mmol/L) 5.7±0.1 5.3±0.1 0.001.
Chambers JC, Kooner JS, 2000, C-reactive protein and coronary heart disease risk in UK Indian Asians, compared to European whites, Heart, Vol: 83, ISSN: 1355-6037
Background: Reasons for the increased coronary heart disease (CHD) mortality in UK Indian Asians are not well understood. In this study, we tested the hypotheses that C-reactive protein (CRP) concentrations are elevated in UK Indian Asians, and contribute to their increased CHD risk, compared to European whites. Methods: We investigated 1,025 healthy male controls (518 Indian Asian, 507 European white) and 551 male cases (myocardial infarction or angiographically proven CHD; 257 Indian Asian, 294 European white). CRP concentrations and conventional CHD risk factors were measured. Results: Mean CRP concentrations were 17% higher (95% confidence interval [Cl] 3-36%) in Indian Asian, compared to European white controls, and were elevated in cases compared to controls in both populations. CRP concentrations were positively associated with CHD risk factors, in particular insulin resistance and BMI, in both racial groups. The difference in CRP concentrations between Indian Asians and European whites was not explained by the presence of conventional CHD risk factors, but was accounted for by the higher level of insulin resistance in Indian Asians. Based on these data, we estimate that inflammatory mechanisms may underlie approximately 50% more CHD deaths in Indian Asians than European whites. Conclusions: CRP concentrations are higher in Indian Asians compared to European whites, and are accounted for by their increased severity of insulin resistance. Our results suggest that inflammatory mechanisms may underlie a proportion of the increased CHD risk amongst Indian Asians.
Chambers JC, Ireland H, Lane D, et al., 2000, The C677T methylenetetrahydrofolate reductase mutation does not explain elevated plasma homocysteine concentrations in UK Indian Asians, Heart, Vol: 83, ISSN: 1355-6037
Background: Coronary heart disease (CHD) mortality is higher in UK Indian Asians (IA) than European whites (EW). Plasma homocysteine concentrations are elevated in IA compared to EW, and may contribute to excess CHD risk in the former. We have investigated the extent to which the methylenetetrahydrofolate reductase (MTHFR) C677T mutation accounts for elevated plasma homocysteine, and increased CHD risk, in IA, compared to EW. Methods: We investigated 454 male CHD cases (myocardial infarction or angiographically proven CHD, 224 IA; 230 EW) and 805 healthy male controls (3811A, 424 EW). Fasting homocysteine concentrations, MTHFR C677T genotype, and conventional CHD risk factors were measured. Results: Fasting homocysteine concentrations were higher in IA than EW controls, and in CHD cases compared to controls in both racial groups. However, the frequency of the 677T MTHFR allele was lower in IA, than EW (15.0% vs 32.7%, P<0.001). Elevated homocysteine concentrations were not associated with 677T MTHFR genotype in IA, unlike EW. TT MTHFR genotype was not a risk factor for CHD in IA (odds ratio 0.4, 95% Cl: 0.1-1.5). Conclusions: The 677T MTHFR allele does not determine plasma homocysteine concentrations in IA. In fact the prevalence of the 677T MTHFR mutation in IA is less than half that in EW, even though homocysteine concentrations are elevated in the former. Our results suggest that other genetic defects and/or environmental influences affecting homocysteine metabolism, may have a more important role in IA.
Chambers JC, Haskard DO, Kooner JS, 2000, Vascular endothelial function and oxidation stress in patients with Behçet's disease, Heart, Vol: 83, ISSN: 1355-6037
Background: Behçet's disease is a multisystem inflammatory disorder, commonly complicated by vascular thrombosis and arterial aneurysm formation. We have tested the hypothesis that vascular endothelial function is impaired in Behçet's disease, and may reflect increased levels of oxidation stress. Methods: We investigated 19 patients with Behçet's disease (aged 18-50 years, 9 male) and 21 healthy volunteers (aged 18-50 years, 10 male). Brachial artery flow-mediated dilatation (endothelium dependent), and glyceryltrinitrate induced dilatation (GTN, endothelium independent), were measured using high resolution ultrasound. To investigate the role of oxidant stress mechanisms, vascular measurements were repeated 1 hour after administration of vitamin C (1g IV) in 12 patients, and 12 controls. Results: Flow-mediated dilatation was reduced in patients compared to controls (0.7±0.9 vs 5.7±0.9 %, p=0.001). In contrast, there were no significant differences in brachial arterial diameter between patients and controls (4.2±0.2 vs 4.0±0.2 mm, p=0.47) or in brachial artery dilatation in response to sublingual GTN (19.7±1.9 vs 19.7±1.2 %, p=0.98). Administration of vitamin C increased flow-mediated dilatation in patients with Behçet's disease (0.2±0.7 to 3.5±1.0 %, p=0.002), but not in controls (4.3±0.6 to 4.7±0.4%, p=0.51). GTN induced dilatation and brachial arterial diameter were unchanged after vitamin C in both groups. Conclusions: Vascular endothelial function is impaired in Behçet's disease, is mediated by oxidant stress, and can be reversed rapidly by vitamin C. Our results provide new insights in mechanisms underlying Behçet's disease, and provide a rationale for therapeutic studies aimed at reducing vascular complication in this disorder.
Chambers JC, Obeid OA, Refsum H, et al., 2000, Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian Asian and European men, LANCET, Vol: 355, Pages: 523-527, ISSN: 0140-6736
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- Citations: 210
Rajkumar C, Aziz O, Chambers J, et al., 2000, Does acute hyperhomocysteinaemia alter arterial compliance?, Journal of Hypertension
Chambers JC, Wander GS, Kooner JS, 2000, Homocysteine and coronary heart disease amongst Indian Asians., Indian Heart J, Vol: 52, Pages: S5-S8, ISSN: 0019-4832
Chambers JC, Obeid OA, Kooner JS, 1999, Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal human subjects, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, Vol: 19, Pages: 2922-2927, ISSN: 1079-5642
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- Citations: 141
Chambers JC, Haskard DO, Kooner JS, 1999, Vascular endothelial function and oxidant stress mechanisms in patients with Behcet's disease, CIRCULATION, Vol: 100, Pages: 212-212, ISSN: 0009-7322
Chambers J, Rowley M, De Swiet M, et al., 1999, Endothelial dysfunction may be an early manifestation of future vascular disease in women with a previous episode of pre-eclampsia, Heart, Vol: 81, ISSN: 1355-6037
Although the clinical manifestations of pre-eclampsia resolve soon after delivery, affected women remain susceptible to recurrent pre-eclampsia, and hypertension, in later life. The mechanisms which underlie this risk have not been identified. We hypothesised that vascular endothelial function is defective in women with a previous pre-eclampsia, and may influence their future risk of hypertension related disorders. We studied 56 consecutive women aged 18-43 yrs, with recent (>3 months) pre-eclampsia, and 41 age matched controls. Brachial artery flow-mediated (FMD, endothelium dependent), and glyceryl trinitrate-induced (GTN, endothelium independent) dilatation, were measured using high resolution ultrasound. Subjects were characterised for major vascular risk factors. FMD was reduced in women with previous pre-eclampsia compared to controls (2.4±0.6 vs 6.0±0.8%, p<0.005). There were no significant differences in GTN induced dilatation (20.7±1.1 vs 23.3±1.1%, p=0.10), or brachial artery diameter (3.5±0.1 vs 3.3±0.1mm, p=0.24) between the groups. Compared to controls, women with previous pre-eclampsia had higher diastolic blood pressure, and HDL cholesterol (p<0.05), but similar total cholesterol, and smoking rates (p=ns). In a multivariate model, reduced FMD in women with previous pre-eclampsia was independent of vascular risk factors (p<0.05). In summary, endothelium dependent dilatation is impaired in healthy young women with a previous episode of pre-eclampsia, independent of risk factors including hypertension. Our findings support the hypothesis that basal endothelial nitric oxide activity is impaired in women with previous pre-eclampsia, and may contribute to their future risk of vascular disorders.
Chambers J, Obeid OA, Karim Y, et al., 1999, Hyperhomocysteinaemia is a novel risk factor for coronary heart disease in UK Indian Asians, Heart, Vol: 81, ISSN: 1355-6037
Premature coronary heart disease (CHD) mortality is 2-fold higher in UK Indian Asians (IA), than European whites (EW), and is not explained by classic risk factors smoking, hypertension and cholesterol. We hypothesised that homocysteine (Hcy) levels are elevated in IA compared to EW, and may account for their increased CHD risk. We studied 564 male CHD patients (265 IA aged 52±7 yrs, 299 EW aged 55±5 yrs) and 1049 age-matched controls (523 IA, 526 EW). Hcy was measured fasting and after a methionine load (100mg/Kg). Subjects were characterised for CHD risk factors, red cell folate, vitamin B12 and vitamin B6. Mean Hcy levels were higher in IA than EW (fasting, 12.7±0.4 vs 11.4±0.2 μmol/l, p=0.001; post-load, 38.4±0.7 vs 36.0±0.5 μmol/l, p=0.001). Fasting Hcy levels were elevated in CHD patients compared to respective controls (IA, 13.6±0.9 vs 12.2±0.4 μmol/l, p=0.001; EW, 12.3±0.4 vs 10.9±0.2 μmol/l, p=0.001). In contrast, post-load Hcy levels did not differ significantly between patients and controls (IA, 39.7±1.1 vs 37.8±0.8 μmol/l, p=0.06; EW, 37.1±0.9 vs 35.4±0.5 μmol/l, p=0.16). Compared to EW, IA had lower folate (394±9 vs 443±11 ng/ml, p=0.001 ), vitamin B12 (307±9 vs 389±13 pmol/l, p=0.001) and similar vitamin B6 (40.1±1.8 vs 39.8±1.5 ng/ml, p=0.86). Hcy levels were inversely related to vitamin B12 (p=0.001) and folate (p=0.001) but were not related to vitamin B6. In multivariate analysis, elevated fasting Hcy was associated with IA race and CHD independently of blood pressure, smoking, total cholesterol, HDL cholesterol, fasting triglycerides and glucose. We conclude that elevated fasting Hcy may contribute to the excess CHD risk in IA compared to EW, and may be amenable to modulation through dietary vitamin supplementation.
Chambers J, Obeid OA, Jean-Marie J, et al., 1999, Increments in plasma homocysteine after dietary animal protein are associated with vascular endothelial dysfunction in human subjects, Heart, Vol: 81, ISSN: 1355-6037
The vascular effects of physiological, diet-induced increments in plasma homocysteine are not known. We hypothesized that there is a graded, inverse relationship between homocysteine concentration and endothelial function, and that physiological increments in plasma homocysteine following methionine or dietary protein induce vascular endothelial dysfunction. We studied 18 healthy volunteers aged 18-59 years. Brachial artery flow-mediated, and glyceryltrinitrate (GTN) induced, dilatation were measured after; i. oral L-methionine (10, 25, 100 mg/kg); ii. dietary animal protein (lean chicken 551±30g, comprising 3.2±0.2g methionine); and iii. methionine-free amino acid mix (100 mg/kg). Methionine (10, 25, 100mg/kg) induced a dose-related increase in homocysteine (9.4±1.3 to 12.2±2.1, 17.6±2.6, and 26.1±4.2 μmol/l, respectively p<0.001), and reduction in flow-mediated dilatation (4.1±0.8 to 2.1±0.8, 0.3±0.8, and -0.7±0.8%, respectively p<0.001) at 4 hours. Compared to usual meal, animal protein increased plasma homocysteine (9.6±0.8 to 11.2±0.9 μmol/l, p=0.005) and reduced flow mediated dilatation (4.5±0.7 to 0.9±0.6%, p=0.003). Methionine-free amino acid mix did not induce any changes. GTN induced dilatation was unchanged throughout. Our results provide evidence of an inverse relationship between homocysteine concentration and endothelial function, and show that physiological increments in plasma homocysteine after low-dose methionine and dietary animal protein are associated with vascular endothelial dysfunction. These results imply that diet related changes in homocysteine may have adverse vascular effects in patients with coronary artery disease.
Chambers JC, McGregor A, Jean-Marie J, et al., 1999, Abnormalities of vascular endothelial function may contribute to increased coronary heart disease risk in UK Indian Asians, HEART, Vol: 81, Pages: 501-504, ISSN: 1355-6037
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- Citations: 54
Chambers JC, McGregor A, Jean-Marie J, et al., 1999, Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia - An effect reversible with vitamin C therapy, CIRCULATION, Vol: 99, Pages: 1156-1160, ISSN: 0009-7322
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- Citations: 377
Chambers J, Kooner JS, 1998, Homocysteine levels are elevated in UK Indian Asian compared to British white men, Heart, Vol: 79, ISSN: 1355-6037
High coronary heart disease (CHD) mortality in UK Indian Asians (IA) is not explained by conventional risk factors. We hypothesized that homocysteine (Hcy) levels are elevated in IA compared to British whites (BW), and may account for their increased CHD risk. We studied 200 IA and 199 BW men, aged 35-61 years, randomly identified from 15 GP lists. Subjects were characterised for CHD risk factors, including insulin resistance, and the nutritional determinants of Hcy, vitamin B12 and red cell folate. Hcy was measured in the fasting state, and after a methionine load (100mg/Kg). Mean Hcy levels were higher in IA than BW (fasting, 11.9±0.7 vs 10.7±0.3 μmol/l, p=0.08; post-load, 37.1±1.5 vs 33.9±0.8 μmol/l, p<0.05). Hyperhomocysteinaemia, defined as the top quintile of the distribution in BW (fasting ≥12.6; post-load ≥38.0 μmol/l), was present in 29% of IA vs 20% of BW in the fasting state (p<0.05), and 32% of IA vs 20% of BW post-load (p<0.05). Hcy levels were inversely related to vitamin B12 (p<0.001) and folate (p<0.001). IA had lower folate (363±128 vs 409±147 ng/ml, p<0.001), and vitamin B12 (307±141 vs 391±169 pmol/l, p<0.001) than BW. IA had higher fasting insulin (13.8±1.0 vs 7.3±0.6 mU/ml, p<0.01), glucose (6.2±0.2 vs 5.6±0.1 mmol/l, p<0.01), waist-hip ratio (0.97±0.01 vs 0.94±0.01, p<0.01), triglycerides (1.82±0.09 vs 1.56±0.09 mmol/l, p<0.01) and lower HDL cholesterol (1.14±0.02 vs 1.28±0.03 mmol/l, p<0.05) compared to BW. Hcy was not associated with markers of insulin resistance. Other risk factors were similar in the two groups. We conclude that Hcy levels are elevated in IA compared to BW. In IA, elevated homocysteine levels are associated with reduced folate and B12, but not with insulin resistance. Hyperhomocysteinaemia may be a novel CHD risk factor in IA and potentially amenable
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