Search

Background South Asia has become a major epicentre of the COVID-19 pandemic. Understanding South Asians’ awareness, attitudes and experiences of early measures for the prevention of COVID-19 is key to improving the effectiveness and mitigating the social and economic impacts of pandemic responses at a critical time for the Region. Methods We assessed the knowledge, behaviours, health and socio-economic circumstances of 29,809 adult men and women, at 93 locations across four South Asian countries. Data were collected during the national lockdowns implemented from March to July 2020, and compared with data collected prior to the pandemic as part of an ongoing prospective surveillance initiative. Results Participants were 61% female, mean age 45.1 years. Almost half had one or more chronic disease, including diabetes (16%), hypertension (23%) or obesity (16%). Knowledge of the primary COVID-19 symptoms and transmission routes was high, but access to hygiene and personal protection resources was low (running water 63%, hand sanitisers 53%, paper tissues 48%). Key preventive measures were not widely adopted. Knowledge, access to, and uptake of COVID-19 prevention measures were low amongst people from disadvantaged socio-economic groups. Fifteen percent of people receiving treatment for chronic diseases reported loss of access to long-term medications; 40% reported symptoms suggestive of anxiety or depression. The prevalence of unemployment rose from 9.3% to 39.4% (P, Highlights • South Asia has become a major epicentre of the COVID-19 pandemic and faces multiple challenges (health, economic, social). • Our findings identified important knowledge, access and uptake barriers to the prevention of COVID-19 in the region. • We demonstrated adverse impacts on chronic disease treatment, mental health, health behaviours, employment, finances. • There is a need for immediate large-scale action to close gaps in knowledge and access to essential resources for prevention. • Along with measures to safeguard economic production and mitigate socio-economic impacts on the young and the poor.

SummaryMetabolic dysregulation in multiple tissues alters glucose homeostasis and influences risk for type 2 diabetes (T2D). To identify pathways and tissues influencing T2D-relevant glycemic traits (fasting glucose [FG], fasting insulin [FI], two-hour glucose [2hGlu] and glycated hemoglobin [HbA1c]), we investigated associations of exome-array variants in up to 144,060 individuals without diabetes of multiple ancestries. Single-variant analyses identified novel associations at 21 coding variants in 18 novel loci, whilst gene-based tests revealed signals at two genes, TF (HbA1c) and G6PC (FG, FI). Pathway and tissue enrichment analyses of trait-associated transcripts confirmed the importance of liver and kidney for FI and pancreatic islets for FG regulation, implicated adipose tissue in FI and the gut in 2hGlu, and suggested a role for the non-endocrine pancreas in glucose homeostasis. Functional studies demonstrated that a novel FG/FI association at the liver-enriched G6PC transcript was driven by multiple rare loss-of-function variants. The FG/HbA1c-associated, islet-specific G6PC2 transcript also contained multiple rare functional variants, including two alleles within the same codon with divergent effects on glucose levels. Our findings highlight the value of integrating genomic and functional data to maximize biological inference.Highlights23 novel coding variant associations (single-point and gene-based) for glycemic traits51 effector transcripts highlighted different pathway/tissue signatures for each traitThe exocrine pancreas and gut influence fasting and 2h glucose, respectivelyMultiple variants in liver-enriched G6PC and islet-specific G6PC2 influence glycemia

Background: DNA methylation at GFI1-locus has been repeatedly associated with exposure to smoking from foetal period onwards. We explored whether DNA methylation maybe a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n=18212). DNA methylation at GFI1-locus was measured in whole-blood. Multivariable regression analyses were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Hypomethylation at four out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Cg14179389 hypomethylation, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0·012. In contrast, hypomethylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 x 10 - 7 < P < 0·01). Similarly, hypo-methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 10 - 8 < P < 0·001). Hypomethylation at all the CpGs was consistently associated with higher TG levels. Interpretation: Epigenetic changes at GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. This introduces a molecular mechanism and biomarker of smoking exposure. Funding: Not applicable Declaration of interests: The authors declare no competing interests. Ethical Approval Statement: Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees.

Background Indian Asians, who make up a quarter of the world's population, are at high risk of developing type 2 diabetes. We investigated whether DNA methylation is associated with future type 2 diabetes incidence in Indian Asians and whether differences in methylation patterns between Indian Asians and Europeans are associated with, and could be used to predict, differences in the magnitude of risk of developing type 2 diabetes. Methods We did a nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population (LOLIPOP) study. Patients were recruited between May 1, 2002, and Sept 12, 2008. We did epigenome-wide association analysis using samples from Indian Asians with incident type 2 diabetes and age-matched and sex-matched Indian Asian controls, followed by replication testing of top-ranking signals in Europeans. For both discovery and replication, DNA methylation was measured in the baseline blood sample, which was collected before the onset of type 2 diabetes. Epigenome-wide significance was set at p

Item does not contain fulltext BACKGROUND: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD. OBJECTIVE: We tested whether common genetic polymorphisms associated with variation in tHcy are also associated with CAD. DESIGN: We conducted a meta-analysis of genome-wide association studies (GWAS) on tHcy concentrations in 44,147 individuals of European descent. Polymorphisms associated with tHcy (P < 10(-8)) were tested for association with CAD in 31,400 cases and 92,927 controls. RESULTS: Common variants at 13 loci, explaining 5.9% of the variation in tHcy, were associated with tHcy concentrations, including 6 novel loci in or near MMACHC (2.1 x 10(-9)), SLC17A3 (1.0 x 10(-8)), GTPB10 (1.7 x 10(-8)), CUBN (7.5 x 10(-10)), HNF1A (1.2 x 10(-12)), and FUT2 (6.6 x 10(-9)), and variants previously reported at or near the MTHFR, MTR, CPS1, MUT, NOX4, DPEP1, and CBS genes. Individuals within the highest 10% of the genotype risk score (GRS) had 3-mumol/L higher mean tHcy concentrations than did those within the lowest 10% of the GRS (P = 1 x 10(-36)). The GRS was not associated with risk of CAD (OR: 1.01; 95% CI: 0.98, 1.04; P = 0.49). CONCLUSIONS: We identified several novel loci that influence plasma tHcy concentrations. Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tHcy concentrations and tHcy-related pathways for CAD.

Objectives The purpose of this study was to define age-, sex-, and ethnicity-specific reference values for 3-dimensional echocardiographic (3DE) left ventricular (LV) volumes and LV ejection fraction (LVEF) in a large cohort of European white and Indian Asian subjects. Background Transthoracic 3DE imaging is recommended for the routine evaluation of LV volumes and function. However, there remains a lack of population-based reference values for 3DE LV volumes and LVEF, hindering adoption of this technique into routine clinical practice. Methods We identified subjects from the LOLIPOP (London Life Sciences Prospective Population) study who were free of clinical cardiovascular disease, hypertension, and type 2 diabetes. All subjects underwent transthoracic 2-dimensional and 3D echocardiography for quantification of LV end-systolic volume index, LV end-diastolic volume index, and LVEF. Results 3DE image quality was satisfactory in 978 subjects (89%) for the purposes of LV volumetric analysis. Indexed 3DE LV volumes were significantly smaller in female compared with male subjects and in Indian Asians compared with European whites. Upper limit of normal (mean ± 2 SD) reference values for the LV end-systolic volume index and LV end-diastolic volume index for the 4 ethnicity-sex subgroups were, respectively, as follows: European white men, 29 ml/m2 and 67 ml/m2; Indian Asian men, 26 ml/m2 and 59 ml/m2; European white women, 24 ml/m2 and 58 ml/m2; Indian Asian women, 23 ml/m2 and 55 ml/m2, respectively. Compared with 3DE studies, 2-dimensional echocardiography underestimated the LV end-systolic volume index and LV end-diastolic volume index by an average of 2.0 ml/m2 and 4.7 ml/m2, respectively. LVEF was similar between in all 4 groups and between 2- and 3-dimensional techniques, with a lower cutoff of 52% for the whole cohort. Conclusions These reference values are based on the largest 3DE study performed to date that should facilitate the standardization of the technique and encourage its adoption for the routine assessment of LV volumes and LVEF in the clinical echocardiography laboratory. This study supports the application of ethnicity-specific reference values for indexed LV volumes.

Background Indian Asians living in the United Kingdom have a >50% higher risk of cardiovascular disease (CVD) death compared with native European whites. The mechanisms underlying their excess mortality are not clear, and there are no validated tools capable of identifying this increased risk. The burden of subclinical atherosclerosis detected in the carotid arteries is an established prognosticator for major CVD events. We hypothesized that the increased prevalence of CVD among Indian Asians would be reflected by their having a greater burden of subclinical carotid artery atherosclerosis compared with European whites. Methods We studied 2,288 healthy subjects and 148 patients with known CVD from the London Life Sciences Prospective Population study who underwent carotid ultrasonography for assessment of intima-media thickness (IMT), plaque prevalence, and plaque echogenicity. Results The prevalence of CVD was significantly higher among Indian Asians compared with European whites (odds ratio 1.72, 95% CI 1.2-2.3). Intima-media thickness was slightly higher in European whites compared with that of Indian Asians (0.66 vs 0.65 mm, P = .06), reflecting their higher Framingham Risk Score. After adjustment for cardiovascular risk factors, there were no significant differences in IMT, plaque prevalence, or plaque echogenicity between the 2 ethnic groups regardless of CVD status. Conclusion The burden of carotid atherosclerosis does not identify the markedly increased risk of CVD among United Kingdom Indian Asians. Other markers and mechanisms of disease require investigation in this high-risk group.

Subclinical carotid atherosclerosis has been associated with impaired left ventricular (LV) function and the development of heart failure. Whether impaired LV function is related primarily to increased intima-media thickness (IMT) or burden of plaque disease or both remains to be determined.A total of 2,279 subjects without clinical cardiovascular disease recruited from the London Life Sciences Prospective Population cohort study were studied. Carotid ultrasonography and transthoracic echocardiography were performed on all subjects. Carotid IMT and plaque scores were measured, and their relationships with LV volumes, LV ejection fraction, myocardial LV longitudinal function (Sa and Ea velocities), and LV filling pressure (E/Ea ratio) were assessed before and after adjustment for covariates.Compared with those without carotid artery disease, subjects with either increased IMT and/or presence of plaque disease had identical Sa velocities (both 9.0 cm/sec), lower Ea velocities (8.7 vs 9.9 cm/sec, P.001) and higher E/Ea ratios (8.4 vs 7.6, P.001). After multiple linear regression analysis, increasing IMT remained independently related to reduced Ea velocity (P.001) but not LV ejection fraction, Sa velocity, or E/Ea ratio. In a separate adjusted analysis, subjects with severe burdens of carotid plaque disease (more than five plaques) had reduced LV ejection fractions (β = -2.9; 95% confidence interval [CI], 1.0 to 4.8, P = .003), attenuated Sa velocities (β = -0.79; 95% CI, -1.2 to -0.3, P = .003), attenuated Ea velocities 2 (β = -0.79; 95% CI, -1.3 to -0.2, P = .007), and increased E/Ea ratios (β = 0.84; 95% CI, 0.2 to 1.5, P = .009) compared to individuals without carotid plaques.These findings demonstrate that subclinical carotid plaque disease rather than IMT is more closely related to LV systolic function and LV filling pressure. These data support the application of carotid ultrasonography beyond cardiovascular disease risk prediction, while providing insight into potential mechanisms underlying the development of subclinical LV dysfunction.

ObjectivesTo explore the differences in psychosocial risk factors related to coronary heart disease (CHD) between South Asian subgroups in the UK. South Asian people suffer significantly higher rates of CHD than other ethnic groups, but vulnerability varies between South Asian subgroups, in terms of both CHD rates and risk profiles. Psychosocial factors may contribute to the excess CHD propensity that is observed; however, subgroup heterogeneity in psychosocial disadvantage has not previously been systematically explored.MethodsWith a cross-sectional design, 1065 healthy South Asian and 818 white men and women from West London, UK, completed psychosocial questionnaires. Psychosocial profiles were compared between South Asian religious groups and the white sample, using analyses of covariance and post hoc tests.ResultsOf the South Asian sample, 50.5% was Sikh, 28.0% was Hindu, and 15.8% was Muslim. Muslim participants were more socioeconomically deprived and experienced higher levels of chronic stress, including financial strain, low social cohesion, and racial discrimination, compared with other South Asian religious groups. In terms of health behaviors, Muslim men smoked more than Sikhs and Hindus, and Muslims also reported lower alcohol consumption and were less physically active than other groups.ConclusionThis study found that Muslims were exposed to more psychosocial and behavioral adversity than Sikhs and Hindus, and highlights the importance of investigating subgroup heterogeneity in South Asian CHD risk.

Background To compare patterns of coronary artery disease in British South Asian and White European men. Methods 41 South Asian and 42 European men (mean age 64±9 years) with coronary artery disease were studied. All had similar symptoms. Vessel reference diameter and degree of stenosis were calculated using quantitative coronary angiography. Extent of atherosclerotic disease in the LAD was assessed using calcification scores (CAC) measured by multislice Computed Tomography. Fasting bloods and blood pressure were measured. The LAD was subdivided into four 2.5 cm segments for analysis. Results Most atherosclerosis occurred in the proximal LAD segment, South Asian men had more proximal LAD stenosis than European men (50% vs. 37%, p =0.036), but CAC scores were similar. South Asians with CAC scores in the lowest tertile (0–22 HU), had significantly narrower LAD diameters than Europeans (2.8 mm vs. 3.8 mm, p =0.004, adjusted for body surface area and age). This ethnic difference was not explained by measured risk factors, including diabetes. In contrast, ethnic differences in LAD diameter were abolished in the upper tertiles of CAC scores (23–2416 HU) (South Asians: 3.0 mm, Europeans: 3.1 mm, p =0.6). Calcification scores were negatively correlated with LAD diameter in Europeans (rho=−0.38, p =0.016) but not in South Asians (rho=−0.06, p =0.72). Conclusions Increased LAD stenosis, despite equivalent levels of calcified disease, in South Asians is attributable to narrower arteries. Reduced LAD diameter is associated with advanced disease in Europeans but not in South Asians, indicative of ethnic differences in vascular remodelling.

Objectives Indian Asians have high rates of heart disease and stroke, but risks of peripheral arterial disease appear to be low. This paradox, and reasons for it, have not been explored. We compared ethnic differences in peripheral arterial disease for a given level of coronary disease. Methods We studied 83 European and 84 Indian Asian men with a range of coronary disease. Extent of coronary atheroma was quantified by coronary artery calcification score on multislice CT. Femoral intima-media thickness (IMT) was measured by ultrasound. Results Femoral IMT was 1.58, 2.06, 2.12, and 2.69mm in Europeans, and 0.61, 1.41, 1.81 and 2.29 in Indian Asians by increasing categories of coronary atheroma ( p =0.003 for ethnic difference, adjusted for age and lumen diameter). Adjustment for smoking and systolic blood pressure, the only risk factors adversely distributed in Europeans, only partly accounted for this ethnic difference ( p =0.05). Other risk factors, including lipids, obesity, insulin and glycaemic status, more adversely distributed in Indian Asians, could not account for ethnic differences. Prevalence of abnormal ankle brachial index and lower limb atherosclerotic plaque was also greater in Europeans. Conclusions For a given level of coronary disease, Indian Asians have less lower limb atherosclerosis than Europeans, unexplained by established risk factors. Further study of these populations would help tease out relative contributions of risk factors to atherosclerosis in different vessel beds.

Background Patients with diabetes have an increased incidence and severity of ischemic heart disease, which leads to an increased requirement for coronary revascularization. Comparative information regarding mode of revascularization—coronary artery bypass graft surgery surgery (CABG) or percutaneous coronary intervention (PCI)—is limited, mainly confined to a subanalysis of the Bypass Angioplasty Revascularization (BARI) trial, suggesting a mortality benefit of CABG over PCI. No prospective trial has specifically compared these modes of revascularization in patients with diabetes. Objective The Coronary Artery Revascularisation in Diabetes (CARDia) trial is designed to address the hypothesis that optimal PCI is not inferior to modern CABG as a revascularization strategy for diabetics with multivessel or complex single-vessel coronary disease. The primary end point is a composite of death, nonfatal myocardial infarction, and cerebrovascular accident at 1 year. Method A total of 600 patients with diabetes are to be randomized to either PCI or CABG, with few protocol restrictions on operative techniques or use of new technology. This gives a power of 80% to detect non-inferiority of PCI assuming that the PCI 1-year event rate is 9%. A cardiac surgeon and a cardiologist must agree that a patient is suitable for revascularization by either technique prior to recruitment into the study. Twenty-one centers in the United Kingdom and Ireland are recruiting patients. Data on cost effectiveness, quality of life, and neurocognitive function are being collected. Long-term (3–5 year) follow-up data will also be collected.

OBJECTIVES We sought to test the hypothesis that vascular endothelial function is impaired in Behcet’s syndrome and reflects increased levels of oxidative stress. BACKGROUND Behcet’s syndrome is a multisystem inflammatory disorder commonly complicated by vascular thrombosis and arterial aneurysm formation. The precise mechanisms underlying vascular disease in Behcet’s syndrome are not known. METHODS We studied 19 patients with Behcet’s syndrome (18 to 50 years old, 9 men) and 21 healthy volunteers (18 to 50 years old, 10 men). Brachial artery flow-mediated dilation (endothelium-dependent), and nitroglycerin (NTG)-induced dilation (endothelium-independent) were measured. To investigate oxidative stress mechanisms, vascular studies were repeated 1 h after administration of vitamin C (1 g, intravenous) in 12 patients and 12 control subjects. RESULTS Flow-mediated dilation was reduced in patients with Behcet’s syndrome as compared with control subjects (0.7 ± 0.9% vs. 5.7 ± 0.9%, p = 0.001). In contrast, there were no significant differences in the brachial artery diameter (4.2 ± 0.2 vs. 4.0 ± 0.2 mm, p = 0.47) or NTG-induced dilation (19.7 ± 1.9% vs. 19.7 ± 1.2%, p = 0.98). In regression analysis, Behcet’s syndrome was associated with impaired flow-mediated dilation independent of age, gender, brachial artery diameter, blood pressure, cholesterol and glucose. Vitamin C increased flow-mediated dilation in Behcet’s syndrome (0.2 ± 0.7% to 3.5 ± 1.0%, p = 0.002), but not in control subjects (4.3 ± 0.6% to 4.7 ± 0.4%, p = 0.51). In both groups, NTG-induced dilation and brachial artery diameter were unchanged after vitamin C treatment. CONCLUSIONS Vascular endothelial function is impaired in Behcet’s syndrome and can be rapidly improved by vitamin C treatment. Our results support a role for oxidative stress in the pathophysiology of Behcet’s syndrome and provide a rationale for therapeutic studies aimed at reducing vascular complications in this disorder.

Summary Background Reasons for the increase in mortality due to coronary heart disease (CHD) in UK Indian Asians are not well understood. In this study, we tested the hypotheses that elevated plasma homocysteine concentrations are a risk factor for CHD in Indian Asians, and explain part of their increased CHD risk, compared with Europeans. Methods We undertook two parallel case-control studies, one in Europeans and one in Indian Asians. We recruited 551 male cases (294 European, 257 Indian Asian) and 1025 healthy male controls (507 European, 518 Indian Asian). Fasting and post-methionine load homocysteine, vitamin B 12 and folate concentrations, and conventional CHD risk factors were measured. Findings Fasting homocysteine concentrations were 8% higher (95% CI 3–14) in cases compared with controls, in both ethnic groups. The odds ratio of CHD for a 5 μmol/L increment in fasting plasma homocysteine was 1·3 (1·1-1·6) in Europeans and 1·2 (1·0-1·4) in Indian Asians. The association between fasting plasma homocysteine and CHD was independent of conventional CHD risk factors in both ethnic groups. Post-load homocysteine concentrations were not significantly different in cases compared with controls. Among the controls, fasting homocysteine concentrations were 6% (2-10) higher in Indian Asians than in Europeans. From the results we estimate that elevated homocysteine may contribute to twice as many CHD deaths in Indian Asians, compared with Europeans. The differences in homocysteine concentrations between the two ethnic groups were explained by lower vitamin B 12 and folate levels in Asians. Interpretation Plasma homocysteine is a novel and independent risk factor for CHD in Indian Asians, and may contribute to their increased CHD risk. Raised homocysteine concentrations in Indian Asians may be related to their reduced vitamin B 12 and folate levels, implying that the increased CHD risk in this group may be reduced by dietary vitamin supplementation.

Though calcium plays an important role in a number of biologic processes related to the pathogenesis of atherosclerosis, the relationship of serum calcium and phosphorus levels with the angiographic severity of coronary artery disease (CAD) is not known. We retrospectively studied 376 stable patients (age range 31-86 years, mean 59.2 +/- 10.5 years; 68% males) undergoing routine coronary angiography and related the angiographic severity of CAD with the serum levels of total and corrected calcium, phosphorus, albumin, total protein and bicarbonate. The primary variable studied was the number of vessels with haemodynamically significant disease. On univariate analysis, total serum calcium and serum albumin levels had a negative association with the number of vessels diseased (P = 0.046 and 0.057, respectively). Multiple regression analysis using age, sex, smoking, diabetes, hypertension, hyperlipidaemia, ethnicity and family history, in addition to serum calcium, phosphorus and albumin levels as the predictor variables, showed that serum albumin has an independent negative and serum phosphorus has an independent positive association with the angiographic severity of CAD (P = 0.04 and 0.003, respectively; n = 294). Serum phosphorus level also showed highly significant positive associations with the presence of total or subtotal occlusion and with most severe stenosis observed on angiography. A moderate change in the serum level of albumin or phosphorus confers a risk similar to that associated with smoking, as estimated by the odds ratios.

We have shown that unlike fat, protein, xylose, or water, the carbohydrate component of the meal accelerates myocardial ischemia, reduces exercise capacity, and is associated with a more rapid increase in the determinants of myocardial oxygen consumption than exercise in the fasting state. Our results suggest a role for a larger increase in sympathetic nervous activity and/or release of vasoactive gastrointestinal peptides after carbohydrates than after other test meals in postprandial angina.

We investigated the role of food constituents in mechanisms contributing to post-prandial angina (PPA). Studies were performed in 8 males (aged 60 ± 3 yrs). with reproducible PPA, after an overnight fast, off drugs (except GTN) for 3 days. HR, BP, rate pressure product (RPPI, time to onset of angina (TA) and 1 mm ST depression (TST), plasma noradrenaline (NOR, nmol/l) and adrenaline (AD, nmol/l, were measured before, 30 min after water (WM), liquid carbohydrate (CM), fat (FM), and protein (PM) meals, and during exercise (Bruce protocol). Meals were isocaloric (1000 cal), isovolumic, and administered in random order, on separate days. HR, BP, and RPP increased to similar levels 30 min after CM, FM and PM, compared to WM. During exercise TA, TST and ED were reduced after CM, but not FM or PM, compared to WM ( * = p l 0.05). RPP was unchanged after CM, but increased after FM and PM, compared to WM. Plasma NOR rose after CM (3.4 ± 0.4 to 4.9 ± 04 * ) and FM (3.1 ± 0.3 to 4.2 ± 0.2 * ), but not after PM or WM. Plasma AD did not rise after meals. Angina 1 mm ST DEP Peak Exercise TA (sec) RPP × 10 -3 TST (sec) RPP × 10 -3 Time (sec) RPP × 10 -3 WM 141 ± 20 16 ± 07 141 ± 20 17 ± 1.2 317 ± 62 18 ± 1.2 CM 109 ± 17 * 18 ± 10 109 ± 17 * 18 ± 1.4 254 ± 66 * 20 ± 1.2 FM 157 ± 59 17 ± 1.0 157 ± 21 19 ± 1.2 * 287 ± 62 20 ± 1.2 PM 149 ± 64 18 ± 0.5 * 149 ± 22 18 ± 1.0 291 ± 65 20 ± 1.1 * Conclusion 1. Decrease in time to angina, 1 mm ST DEP, and peak exercise occur after carbohydrate meal but not fat meal or protein meal. 2. This is not accompanied by a rise in rate-pressure product after carbohydrate meal unlike fat meal and protein meal. 3. Decreased exercise threshold to post-prandial ischaemia after carbohydrate meal occurs independently of increased myocardial oxygen consumption, suggesting ‘steal’ mechanisms contribute.

We have investigated the haemodynamic and hormonal responses to angiotensin converting enzyme inhibition in 12 patients with primary autonomic failure (AF, 5 pure autonomic failure, 7 multiple system atrophy) and 7 normal subjects. Measurements of blood pressure (BP), heart rate (HR), stroke distance (SO) and cardiac index (CI, continuous wave Doppler, forearm blood flow (FBF, strain gauge plethysmography) and digital skin blood flow (DSBF, laser Doppler flowmetry) were made non-invasively. Plasma renin activity (PRA) and noradrenaline (NGRAD) were measured before and at 30 min intervals after captopril (50 mg, oral). Basal supine BP was higher in AF compared to normals (p l 0.05). After captopril, mean BP fell in AF (117 ± 6 to 103 ± 5 mmHg, p l 0.05). but not in normals (99 ± 4 to 97 ± 5 mmHg, ns). HR was unchanged after captopril in both groups. The depressor response in AF was accompanied by a fall in SD (9.6 ± 1.2 to 7.6 ± 0.7 cm, p l 0.05) and in CI (676 ± 79 to 536 ± 65 cm/min, p l 0.05). SD and CI were unchanged after captopril in normals (SD, 7.7 ± 1.3 to 7.4 ± 0.6 cm; CI. 579 ± 117 to 571 ± 69 cm/min, both ns). There was no reduction in forearm or digital skin vascular resistance after captopril in either group. Basal PRA in AF was similar to normals, but did not rise after captopril (691 ± 217 to 681 ± 221 pg/ml/hr, ns), unlike normals (813 ± 103 to 1360 ± 290 pg/ml/hr, p l 0.05). NORAO was unchanged after captopril in both groups. We conclude that. captopril lowers blood pressure in AF, unlike normals. The depressor response in AF occurs independently of plasma renin levels and sympathetic nervous activity, suggesting that alternative mechanisms, including accumulation of bradykinin and prostaglandins, may be responsible.