An investigation of restriction fragment length polymorphisms (RFLPs) and association with blood pressure was carried out for the candidate genes coding for renin (REN) and atrial natriuretic peptide (ANP). The relationship between blood pressure, REN and ANP gene RFLPs was tested in a population of black Afro-Caribbean and white European subjects sampled randomly from family practice registers. Upper and lower quintiles for diastolic blood pressure were selected for analysis. Digests of DNA were prepared from leucocytes and RFLPs were determined using Southern blotting analysis with REN and ANP gene probes. There were highly significant ethnic differences found for Bg/I, Bg/ll and Taql polymorphisms with 5'REN probe and for Bg/I polymorphism with an ANP probe. There was also an association between blood pressure and the Bg/I/REN polymorphism in Afro-Caribbeans but not with any other polymorphisms studied in either ethnic group. The findings show significant ethnic RFLP differences at the gene loci for both renin and ANP and provide evidence for a possible link between variations within or close to the renin gene and elevated blood pressure in Afro-Caribbeans.
x openinii this (lisclissioni it is my intention to give a. brief review of our knowledge of intestinal bacte'ria, to: liscuss the subjoet in genceral; 'and to omit as far 'as is possible teclhnical-matter-of -laboratory nature.--Thebacterial flora of the -intestine of tlhe adult is-extremelv complicated, and I' thliik -it mayr be approached most easily by a studv of the development of these organisms iin the inifanit.In the newly born infant the meco6ihium is sterile, b)ut organisms appear in small niulmbers within the first twenity-four liours.Durinig the first few days the organisms mnost frequently founid aile StapljIeloceccus'albus, iStreptococclis faccalis, and meembers of the Bacillus coli' group.With the first sample of meconium-free faieces short, slender, Gram-positive bacilli appear, to which Tissier gave the niame Bacillus bifiduls.In the neext few days there is a rapid increase in these organisms and a dimiiinution in the coliform and other organisms until a film of tlhe stool shows practically nio otlher bacteria, -althouigh by cultural methods coliform organisms, strepto- 'cocci, staphvlocotci, 'and spore-bearing organismsca'n be'shown to be present in small numbers.So -long as -breast-feeding is the only means ofinourislhment the" -bacterial flora of the infanit's faeces is predominantly of' the B. bifidg.stype, 95 per cent. of the organisms in a' 'film being of this type.The flora of infants w-ho are artificially fed slioivs greater complexity, and -the pre- dominanlt orgaisnism are of coliform type.Streptococci are found in greater numbers than in the suckling's stool, and spore-bearing organisms are present in most cases.The facces of breast-fed infants are always distinctlv acid in reactioni, wlhereas the stools of the artificially fed chiildreni are alkaline or neutral.This difference iln reaction of the stools of the breast-fed inifant anid tlhose of tlhe artificiallv fed is of conisiderable importance in relation to the types of bacterial flora.The alkalinity of the faeces of infanits fed on cow's milk has been attributed by Miller to the actioni of putrefactive bacteria on the large amount of proteini whliclh is present ill couw's milk as compared with hluman milk, w-hile Schlossmanin believes that the impor- tant factor is tlhe protein fat ratio.The acidity of the suckling's stool lhas been attributed to the hiiglh content of -lactose in the breast milk, an-d it has been showni experi- mentally that the addition of lactose to the dietary of rats results in hiiglily acid contents of the caecum wlhereas a hiiglh protein diot does not plroduce this.Cltu:k and 'Marriott have suggested that the poverty of huma'n milk in buffer salts allows of a rapid .change in the reaction, and the acids produced -are free to act upon the intestinal miucosa, cansing a rapid evacuatioln of the contents and aan acid stool.In support of this is the observationi that in diarrlhoeal conditionis the stools are usually acid as compared with normal.It lhas been establislhed that B. bifidus anid related organisms of the B. acidophilus type can survive exposure to highl-acid.fluids' which destroy coliform organisms, anid the predominance of these organisms in the stool of the breast-fed infanit and the poverty in coliform organlisms has been attributed to the acid reaction of the intestinal contents.The absenice of spore-bearing oiganisms in the suckling's stool is attributed to the same factor, anid it has been shown that the growth of these organisms is markedly inhibited in highly acid media in which B. bifiduis anid B. acidophlut.), survive.Some workers, however, are of opiniioni that the acidresistanit organisms are directly anitagoniistic to the growth of B. coli and the spore-bearing anaerobes.* Given in op2ning a discussion in the Section of Patlhology and Bacteriolocz at the Annual MIeeting of the British Medical Association, Cardiff, 1928.After the period of breast-feeding the chiid is quicklv introduced-to a variety of foodstuffs, and during adolescence and adult life manyv kin-ds o'f proteins and carbohydrates are ingested; Opportunity is-offered for the invasion 'of tlhe alimentary tract by many organisms, and the bacterial
Abstract Background Epidemiological and animal studies suggest the potential of dietary nitrate (NO 3 − ) to inhibit atherogenesis. Spironolactone may improve arterial stiffness. We tested if 6 months’ intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness versus placebo/doxazosin, to control for blood pressure (BP), in a population with or at risk of type 2 diabetes [1]. Methods A subgroup of participants in our double-blind, randomized-controlled, factorial VaSera trial were randomized to nitrate-containing beetroot juice or nitrate-depleted juice, and spironolactone or doxazosin. Ultrasound for carotid diameter (CD, mm) and intima-media thickness (CIMT, mm) was performed at baseline, 3- and 6-months. Carotid stiffness (CS, m/s) was estimated from aortic pulse pressure (Arteriograph®) and carotid lumen area. Data was analysed by modified intention-to-treat and mixed-model effect, adjusted for confounders. Results 93 participants had a baseline evaluation; 86% had follow-up data. No statistical interactions occurred between the juice and drug arms. BP was similar between the juices and between the drugs. CIMT was significantly lower following nitrate-containing, compared with placebo juice [−0.06 (95% Confidence Interval −0.12, −0.01), p = 0.022], with no effect on CD. CS reduction was similar between juices [−0.38(−0.67, −0.10) with placebo, −0.13 (−0.42, 0.16) with active juice] and the drugs [−0.30(−0.58, −0.02) with doxazosin, −0.21(−0.51, 0.09), with spironolactone]. No differences were detected between spironolactone or doxazosin on CIMT and CD. Conclusion 6 months’ intervention with dietary nitrate influences vascular remodelling, but not carotid stiffness or diameter. Neither spironolactone nor doxazosin had a BP-independent effect on carotid structure and function.
Purpose of review Blood lipoprotein profiles in early life are known to be related to and predictive of those in adulthood, but little is known about their determinants. Genetic and environmental influences affect cord blood lipoproteins, but how this occurs and the relative contribution of these influences to the overall profile in healthy newborns remains uncertain. Recent findings This review discusses findings from a range of earlier and more recent studies, and summarizes the key influences on cord blood lipoproteins. In particular, we review the potential contribution of maternal blood total cholesterol levels during pregnancy and the increased maternal transmission in newborns of mothers with diabetes. Summary In cord blood, cholesterol levels are lower than in adults and the relative proportion present in HDL as opposed to LDL is much higher. The currently available evidence suggests that several factors influence the composition of cord blood lipoproteins. Although inheritance of major monogenic disorders can affect cord lipids in general, the genetic contribution appears to be minimal, although effects of the proprotein convertase subtilisin/kexine type 9 gene (PCSK9) need fuller exploration in this regard in certain ethnic groups. Evidence is summarized that maternal lipoprotein levels, particularly those due to diet or induced by pregnancy, influence cord lipid levels. Placental insufficiency and other conditions affecting fetal growth and the mode of delivery may also influence cord lipoprotein concentrations. How maternal glucose tolerance during pregnancy affects cord blood lipoproteins remains unclear. In view of increasing evidence that cardiovascular risk may have prenatal antecedents, this would seem to be an important area for further investigation.
To examine the role of insulin as a cardiovascular risk factor in British Asian and white men.Case-controlled study of survivors of first myocardial infarction.District general hospital.Consecutive series of 76 white and 74 Asian men who survived first myocardial infarction compared with 58 white and 61 Asian male controls without coronary artery disease who were randomly sampled from the community.More Asians than white subjects had impaired glucose tolerance or overt diabetes as measured by the two hour glucose tolerance test (23/74 (32%) v 11/76 (15%) (p less than 0.001) among patients; 17/61 (28%) v 3/58 (6%) (p less than 0.001) among controls). Insulin and C peptide concentrations were higher in both patient groups than in respective controls (p less than 0.001) and higher in Asian than in white subjects, irrespective of their glucose tolerance. Triglyceride concentrations were higher in patients than in controls (1.92 (SD 1.05) v 1.43 (0.82) mmol/l among Asian men; 1.65 (0.83) v 1.3 (0.61) mmol/l among white subjects; p less than 0.001). Total cholesterol concentrations were lower in both groups of Asians than in respective white subjects (5.78 (0.99) v 6.22 (1.04) mmol/l (p less than 0.01) among patients; 5.54 (1.01) v 5.65 (1.11) mmol/l (p less than 0.6) among controls). High density lipoprotein cholesterol concentrations were lower in Asian than in white subjects. The ratio of total cholesterol to high density lipoprotein cholesterol was significantly higher (p less than 0.001) in both patient groups (6.69 (1.81) in Asian patients and 6.31 (1.91) in white patients) than in respective controls (5.24 (1.19) and 4.77 (1.43)). Regression analysis identified C peptide concentration and the ratio of total to high density lipoprotein cholesterol as powerful independent predictors of myocardial infarction in Asian and white men. Total cholesterol concentration predicted infarction in white but not in Asian men.Secretion and hepatic extraction of insulin are high in survivors of myocardial infarction and especially high in British Asians. Tissue resistance to the action of insulin, giving rise to increased pancreatic secretion, may be an important risk factor for coronary artery disease in both ethnic groups and may be partly responsible for the high incidence of diabetes and coronary artery disease in Asian populations.
Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Guy"s and St Thomas" Charity University College London Hospitals Biomedical Research Centre Background Obesity and cardiovascular disease are associated, but the relationship is poorly understood. Myocardial perfusion, metabolic derangement and lipotoxicity appear adversely associated in many scenarios (myocardial injury, diastolic dysfunction, diabetes). Altered perfusion (by PET) predicts outcome, and it is hypothesised that perfusion derangement is part of causality for cardiac disease and adverse outcomes. Purpose To assess the presence and pattern of myocardial microvascular dysfunction in patients with obesity (scheduled for bariatric surgery) using stress quantitative perfusion mapping. Methods 38 subjects with obesity planned to undergo bariatric surgery and 38 age and sex matched healthy volunteers (no diabetes, no hypertension) underwent anthropometry, biochemistry and CMR at 1.5T (Siemens) with cine imaging, stress (adenosine 140-210 mcg/kg/min) and rest fully-automated quantitative perfusion mapping. Results Bariatric patients had a higher BMI (44 ± 6.4 vs 26.5 ± 4kg/m2 p = 0.001); 58%(22) were diabetic and 58%(22) had hypertension. Bariatric patients had higher absolute but lower indexed end-diastolic volumes, and overall higher ejection fractions (+5%) (see Table). Rest myocardial blood flow (MBF) in bariatric patients was the same (1.00 ± 0.3 vs 0.88 ± 0.24 p = 0.052), but stress perfusion results were significantly lower both for stress MBF (2.35 ± 0.69 vs 2.93 ± 0.76ml/g/min p = 0.001) and myocardial perfusion reserve (MPR 2.48 ± 0.82 vs 3.4 ± 0.81ml/g/min p = 0.0001). Although this was transmural, the endocardial stress MBF was particularly negatively affected in the bariatric cohort compared to controls (endocardial MBF 2.16 ± 0.65 vs 2.82 ± 0.73ml/g/min, p = 0.0001 vs epicardial MBF: 2.52 ± 0.76 vs 3.06 ± 0.79 p = 0.003), meaning there was an increased endo-epicardial stress MBF gradient in bariatric patients (0.87 ± 0.12 vs 0.92 ± 0.07 p = 0.03). Conclusion Compared to healthy controls, patients with obesity have abnormal myocardial stress perfusion with reduced global perfusion, perfusion reserve and an increased transmyocardial perfusion gradient. Table - myocardial perfusion parameters Category Bariatric patients n = 38 Controls n = 38 p value Age (years) 48 ± 11 45 ± 13 0.25 n male (%) 12 (32%) 10 (36%) 0.32 LVEDV (ml) 168 ± 37 149 ± 31 0.017 LVEDVi (ml/m2) 70.4 ± 12.3 78.8 ± 12.1 0.004 LV Mass (g) 116 ± 31 99 ± 28 0.019 EF (%) 70 ± 8 65 ± 5 0.002 LVEDV - left ventricular end-diastolic volume, EF - ejection fraction
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