Showing papers by "Nilesh J. Samani published in 2000"

Significant association of caga positive helicobacter pylori strains with risk of premature myocardial infarction

Abstract: OBJECTIVE—To investigate whether genetic diversity of Helicobacter pylori influences its association with coronary heart disease, and specifically whether the risk is confined to infection with the more virulent strains bearing the cytotoxin associated gene-A (cagA) antigen. DESIGN AND SETTING—Case-control study in hospital admitting unselected patients with myocardial infarction. METHODS AND SUBJECTS—Serological status for cagA and H pylori were determined in 342 cases of acute myocardial infarction and 214 population based control subjects free of clinical coronary heart disease. RESULTS—38.0% of cases and 30.8% of controls were cagA seropositive (odds ratio 1.38, 95% confidence interval (CI) 0.94 to 2.01, p = 0.08). In subjects < 65 years old (153 cases, 153 controls), cagA seropositivity was associated with a 1.80-fold increase (95% CI 1.07 to 3.03, p = 0.02) in myocardial infarction risk, which increased further to 2.25-fold (95% CI 1.12 to 4.53, p = 0.01) in subjects < 55 years. There was no significant association of cagA status with classical coronary heart disease risk factors. H pylori seropositivity was present in 60.2% of cases and 53.7% of controls (odds ratio 1.12, 95% CI 0.83 to 1.51, p = 0.43). H pylori seropositivity was not increased in young cases and did not show any interaction with age. CONCLUSIONS—The association of chronic H pylori infection with risk of myocardial infarction appears to be restricted to cagA bearing strains. The association is age dependent and stronger in younger subjects. Genetic heterogeneity of H pylori may explain some of the discordant findings with regard to the association of H pylori with coronary heart disease. Keywords: coronary heart disease; risk factors; Helicobacter pylori

Coronary artery disease: combined stress MR imaging protocol-one-stop evaluation of myocardial perfusion and function.

Abstract: The authors developed and tested a dual stress magnetic resonance (MR) imaging protocol to evaluate myocardial perfusion, function, and hibernation. The technique was well tolerated, and high-quality images were achieved. The comprehensive information obtained can be used to guide clinical management decisions regarding coronary artery revascularization procedures. This protocol offers a one-stop assessment of patients with coronary artery disease with use of a clinical MR imager.

Association analysis of β2 adrenoceptor polymorphisms with hypertension in a Black African population

Abstract: Objective To determine whether or not β 2 adrenoceptor polymorphism is a risk factor for the development of hypertension in a Black South African population Background Attenuated vasodilator responses to endogenous catecholamines may contribute to the aetiology of hypertension. Downregulation of β 2 adrenoreceptors (β 2 AR) following stimulation with agonists is determined in part by variation at the β 2 AR gene locus. The Glu 27 β 2 AR genotype results in attenuated downregulation compared with the wild-type Gln 27 receptor, whereas Gly 16 exhibits enhanced downregulation compared to Arg 16 . Possible racial differences in the prevalence of the β 2 AR polymorphisms may be an explanation for the blunted responses to isoprenaline and the increased prevalence of hypertension in Black African populations. Methods One hundred and ninety-two unrelated hypertensives and 123 normotensives of Black South African origin were studied. Hypertensives were recruited from hospital hypertension clinics in the province of Gauteng and if on treatment, had a 2-4 week washout period before 24-h ambulatory blood pressure assessment Normotensive controls were recruited from the same community. Results There was no significant association between either the Arg-Gly 16 polymorphism or the Gln-Glu 27 polymorphism and hypertension status. Furthermore, in the hypertensives, no significant association was seen between β 2 AR genotype at either site and clinical blood pressure, 24-h blood pressure or left ventricular mass. A significant association was seen between Arg 16 homozygotes and lower body mass index in hypertensives (P = 0.007) although this was not a primary end point Interestingly, the Glu 27 polymorphism was much rarer in this population (allelic frequency 17%) compared to a Caucasian population. Conclusion These data suggest that β 2 AR polymorphism is not a risk factor for hypertension per se in this defined population. The possibility that the decreased prevalence of Glu 27 in black South African populations explains blunted vasodilator responses to isoprenaline requires further study.

Endomyocardial fibrosis associated with antiphospholipid syndrome

Abstract: A 50 year old woman presented with axillary vein thrombosis and was diagnosed as having the antiphospholipid syndrome. The patient also had hypereosinophilia and developed features of severe right heart failure. A transthoracic echocardiogram …

Pharmacogenomics of hypertension: a realizable goal?

Abstract: It is common clinical experience that individual patients vary in their response to different types of anti-hypertensive drugs. The best recognized example of this is the much poorer response of black subjects to angiotensin-converting enzyme (ACE) inhibitors compared with that of Caucasians. However, even within a relatively homogeneous group, individual responses vary greatly. This was shown recently by Dickerson et al. [1] in their study of 56 white patients (aged 22–51 years) from the East Anglia region of the U.K., with previously untreated essential hypertension, who were rotated through the four main classes of anti-hypertensive drugs (diuretics, β-blockers, calcium antagonists and ACE inhibitors). Only 22 out of 56 (39%) individuals achieved the target blood pressure with their first drug, but this increased to 41 out of 56 (73%) when the best response was considered, supporting the concept of individual variability in anti-hypertensive response. There was some correlation between the responses to ACE inhibitors and β-blockers (r# ̄ 0.25) and between those to diuretics and calcium antagonists (r# ̄ 0.36), but not between the other four pairings of treatments. Currently few, if any, clinical or biochemical parameters provide a useful guide as to whether a subject will respond well to a particular class of anti-hypertensive drug. Renin–sodium profiling has been advocated as a means of distinguishing hypertension that is volume dependent (and therefore likely to respond to diuretics) from hypertension that is renin dependent [and therefore likely to respond to drugs that inhibit or antagonize the renin–angiotensin system (RAS)] [2]. However, such profiling has, so far, found little utility in routine clinical practice. Therefore, from an efficacy viewpoint, the choice of initial anti-hypertensive drug is largely empirical. A variety of factors influence the decision, including cost, trial evidence or perceived benefit, guidelines from learned bodies, the presence of other disorders which may encourage (e.g. ACE inhibitors when there is left ventricular dysfunction) or exclude (e.g. β-blockers in presence of asthma) the use of particular drugs, and fashion. The study of Dickerson et al. [1] shows the shortcomings of the current empirical approach. Their findings suggest that, unless one is prepared to go through the laborious process of rotating those patients who do not initially respond adequately through different classes of drugs, many patients will either remain inadequately treated or have additional drugs unnecessarily added in when one would have sufficed. The potential cost, both financially and in terms of morbidity, is enormous. The reasons for the inter-individual variation in responses to anti-hypertensive agents are poorly understood. Although genetically determined variation in drug metabolism that could impact on bioavailability has been documented for some anti-hypertensive agents, this is likely to be only a minor factor. Most of the variation is probably a direct consequence of the heterogeneity of mechanisms underlying ‘essential ’ hypertension. Since genetic factors make a significant contribution to this heterogeneity, a hope that is often expressed is that elucidation of the nature of the inherited factors and a better molecular characterization of hypertension may allow a more informed therapeutic choice to be made. Indeed, this potential provides a key reason for justifying research funding in this area. Several genes have now, at least tentatively, been linked and}or associated with essential hypertension [3]. In the RAS, these include polymorphisms in the angiotensinogen gene, the ACE gene and the angiotensin II subtype 1 receptor gene. However, current evidence that these genetic variants significantly influence blood pressure responses to drugs that antagonize or inhibit the RAS is weak. This is particularly surprising as, at least in the case of the angiotensinogen and ACE genes, the polymorphisms influence plasma levels of their respective protein products. A likely explanation is that, under normal circumstances, these changes are not sufficient to affect the activity of the RAS. A more exciting observation has recently been reported in relation to the adducin gene. Adducin is an α}β heterodimeric protein found in the renal tubule, and is thought to regulate ion transport through changes in the actin cytoskeleton. A Gly-460 ! Trp polymorphism in the α adducin gene has been variably associated with hypertension, and the Trp460 allele has been shown to increase proximal tubular reabsorption [4]. In two separate hypertensive Italian cohorts, subjects carrying the Trp-460 variant have been found to show a much greater fall (by as much as 70–100%) in blood pressure after a thiazide diuretic than subjects carrying only the Gly-460 allele [5]. The findings require replication in other populations but, if confirmed, could provide a valuable means of identifying individuals who are more likely to show a greater blood pressure response to diuretic treatment, since the Trp-460 allele occurs in up to 20% of European Caucasians. A further example relates to the epithelial sodium channel. A mutation in the β subunit (T594M) has been reported to be almost four times more common in hypertensive compared with normotensive black subjects living in