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Biomedical subjects

J Danesh

Publications and source records attributed to J Danesh.

At least 37 records · Page 2Linked to original sources
PubMed1999

Helicobacter pylori infection and early onset myocardial infarction: case-control and sibling pairs study.

OBJECTIVES: To examine the association between coronary heart disease and chronic Helicobacter pylori infection. DESIGN: Case-control study of myocardial infarction at young ages and study of sibling pairs with one member affected and the other not. SETTING: United Kingdom. PARTICIPANTS: 1122 survivors of suspected acute myocardial infarction at ages 30-49 (mean age 44 years) and 1122 age and sex matched controls with no history of coronary heart disease; 510 age and sex matched pairs of siblings (mean age 59 years) in which one sibling had survived myocardial infarction and one had no history of coronary heart disease. MAIN OUTCOME MEASURES: Serological evidence of chronic infection with H pylori. RESULTS: 472 (42%) of the 1122 cases with early onset myocardial infarction were seropositive for H pylori antibodies compared with 272 (24%) of the 1122 age and sex matched controls, giving an odds ratio of 2.28 (99% confidence interval 1.80 to 2.90). This odds ratio fell to 1.87 (1.42 to 2.47; P<0.0001) after smoking and indicators of socioeconomic status were adjusted for and to 1.75 (1.29 to 2.36) after additional adjustment for blood lipid concentrations and obesity. Only 158 of the 510 pairs of siblings were discordant for H pylori status; among these, 91 cases and 67 controls were seropositive (odds ratio 1.33 (0.86 to 2.05)). No strong correlations were observed between H pylori seropositivity and measurements of other risk factors for coronary heart disease (plasma lipids, fibrinogen, C reactive protein, albumin, etc). CONCLUSION: In the context of results from other relevant studies, these two studies suggest a moderate association between coronary heart disease and H pylori seropositivity that cannot be fully accounted for by other risk factors. But even if this association is causal and largely reversible by eradication of chronic infection, very large randomised trials would be needed to show this.

Adult↗
PubMed1999

Coronary heart disease and iron status: meta-analyses of prospective studies.

BACKGROUND: Studies of iron status and coronary heart disease (CHD) have yielded conflicting results. In a systematic review ("meta-analysis"), we quantitatively assessed epidemiological associations reported in prospective studies. METHODS AND RESULTS: Studies were identified by computer-assisted searches of the published literature, scanning of relevant reference lists, hand searching of relevant journals, and discussions with relevant authors. The following was abstracted: size and type of cohort, mean age, mean duration of follow-up, assay methods, degree of adjustment for confounders, and relationship of CHD risk to the baseline assay results. Twelve studies were identified, involving a total of 7800 CHD cases, with several reporting on >1 marker of iron status. For serum ferritin, with 570 CHD cases in 5 studies, comparison of individuals with baseline values >/=200 versus <200 microg/L yielded a combined risk ratio of 1.0 (95% CI, 0.8 to 1.3). For transferrin saturation, with 6194 CHD cases in 5 studies, comparison of individuals in the top third with those in the bottom third of the baseline measurements yielded a combined risk ratio of 0.9 (95% CI, 0.7 to 1.1). Comparisons of individuals in top and bottom thirds of baseline measurements also yielded nonsignificant risk ratios in combined analyses of studies involving total iron-binding capacity (combined risk ratio, 1.0; 95% CI, 0.7 to 1.5), serum iron (0.8; 95% CI, 0.7 to 1.0), and total dietary iron (0.8; 95% CI, 0.7 to 1.1). CONCLUSIONS: Published prospective studies do not provide good evidence to support the existence of strong epidemiological associations between iron status and CHD.

Coronary Disease↗
PubMed1999

Helicobacter pylori infection and gastric cancer: systematic review of the epidemiological studies.

BACKGROUND: The published epidemiological studies of chronic Helicobacter pylori infection and gastric cancer yield conflicting results, so there is uncertainty as to whether any material association exists and, if so, how strong it is. AIM: To review these studies quantitatively. METHODS: A systematic review of sero-epidemiological studies published before 1998 of H. pylori and gastric cancer, as identified by computer-assisted literature searches of relevant journals, reference lists and discussions with authors. All relevant studies identified were included, subdivided by study design. The following was abstracted from published reports: adjusted odds ratio (or, in prospective studies, the risk ratio) and confidence interval, study design, type of controls, mean age, mean duration of follow-up, assay methods, location of study, and degree of adjustment for confounders. RESULTS: The 34 retrospective studies included in total 3300 gastric cancers, but their controls were of uncertain validity. The 10 'nested' case-control comparisons in prospective studies included in total only 800 gastric cancers, and combined analysis of them yielded a risk ratio of 2.5 (95% CI: 1.9-3.4; 2P < 0.00001) for gastric cancer in people seropositive for H. pylori antibodies. CONCLUSIONS: The prospective studies suggest that gastric cancer is 2 or 3 times as common in those chronically infected by H. pylori, but to help investigate causality, further observational studies are still needed, as are large-scale randomized trials of whether antibacterial regimens reduce the eventual incidence of gastric cancer.

Epidemiologic Studies↗
PubMed1999

Risk factors for coronary heart disease and acute-phase proteins. A population-based study.

AIMS: Circulating levels of C-reactive protein and serum amyloid A protein increase markedly, and albumin levels fall, during the acute-phase response to tissue injury, infection and inflammation. Some acute-phase proteins have been associated with increased risks of coronary heart disease in long-term prospective studies. The aim of the present study was to determine whether circulating concentrations of C-reactive protein, albumin and serum amyloid A protein are correlated with one another, standard vascular risk factors, markers of persistent infection, or indicators of socio-economic status. METHODS AND RESULTS: We report a cross-sectional study of 704 individuals without a history of coronary heart disease from five general practices in Bedfordshire, U.K. Plasma levels of C-reactive protein and serum amyloid A protein were strongly associated with each other (2 P<0.00001) and inversely related to levels of serum albumin (2 P<0.00001). There were highly significant associations of plasma C-reactive protein concentrations with cigarette smoking and obesity (2 P<0.00001 for each). Serum albumin levels were strongly associated with blood pressure (2 P<0.0001) and plasma lipids (2 P<0.001), and concentrations of serum amyloid A protein were strongly correlated with obesity (2 P<0.0001). CONCLUSION: Previously reported long-term prospective studies have found an increased risk of coronary heart disease of about 50% in people with raised baseline levels of plasma C-reactive protein or low albumin. The strong cross-sectional associations we have found between levels of these proteins with each other and with concentrations of serum amyloid A protein suggest that some underlying process related to inflammation is likely to be of relevance to the causation of disease. Further studies are needed to determine if the strong associations of plasma levels of C-reactive protein with cigarette smoking and obesity indicate that this particular protein can mediate some of the effects of those risk factors on coronary heart disease.

Acute-Phase Proteins↗
PubMed1999

Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: population based study of coronary heart disease.

OBJECTIVE: To study possible associations between coronary heart disease and serological evidence of persistent infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus. DESIGN: Population based, case-control study, nested within a randomised trial. SETTING: Five general practices in Bedfordshire, UK. INDIVIDUALS: 288 patients with incident or prevalent coronary heart disease and 704 age and sex matched controls. RESULTS: High concentrations of serum IgG antibodies to H pylori were present in 54% of cases v 46% of controls, with corresponding results for C pneumoniae seropositivity (33% v 33%), and cytomegalovirus seropositivity (40% v 31%). After adjustments for age, sex, smoking, indicators of socioeconomic status, and standard risk factors, the odds ratios (95% confidence intervals) for coronary heart disease of seropositivity to these agents were: 1.28 (0.93 to 1.75) for H pylori, 0.95 (0.66 to 1.36) for C pneumoniae, and 1.40 (0.96 to 2. 05) for cytomegalovirus. CONCLUSIONS: There is no good evidence of strong associations between coronary heart disease and serological markers of persistent infection with H pylori, C pneumoniae, or cytomegalovirus. To determine the existence of moderate associations between these agents and disease, however, larger scale studies will be needed that can keep residual confounders to a minimum.

Adult↗
PubMed1999

Risk factors for coronary heart disease and persistent infection with Chlamydia pneumoniae or cytomegalovirus: a population-based study.

BACKGROUND: A large number of epidemiological and pathological studies have reported on associations between coronary heart disease and persistent infection with Chlamydia pneumoniae or cytomegalovirus, but relatively few have reported on possible relations between these infections and vascular risk factors. OBJECTIVE: To determine whether serum concentrations of immunoglobulin G antibodies to C. pneumoniae or cytomegalovirus are correlated to standard vascular risk factors, markers of inflammation and indicators of socioeconomic status. METHODS: We performed a cross-sectional sero-epidemiological study nested within a randomized trial involving five general practices in Bedfordshire, UK. We made measurements of a number of standard vascular risk factors, serum markers of systemic inflammation and other relevant characteristics in 704 individuals. RESULTS: There were significant associations between C. pneumoniae immunoglobulin G levels and male sex and cigarette smoking (2P < 0.01 for each) and between cytomegalovirus immunoglobulin G levels and age (2P < 0.001). Other factors were not significantly associated with serum antibodies to either persistent infection. CONCLUSIONS: Serological evidence of persistent infection with C. pneumoniae or cytomegalovirus in this population was not strongly associated with most standard vascular risk factors and other characteristics. The main implication is that such risk factors are not likely to be important confounders or mediators of the reported associations between coronary heart disease and these agents.

Adult↗
PubMed1998

Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies.

CONTEXT: A large number of epidemiologic studies have reported on associations between various "inflammatory" factors and coronary heart disease (CHD). OBJECTIVE: To assess the associations of blood levels of fibrinogen, C-reactive protein (CRP), and albumin and leukocyte count with the subsequent risk of CHD. DATA SOURCES: Meta-analyses of any long-term prospective studies of CHD published before 1998 on any of these 4 factors. Studies were identified by MEDLINE searches, scanning of relevant reference lists, hand searching of cardiology, epidemiology, and other relevant journals, and discussions with authors of relevant reports. STUDY SELECTION: All relevant studies identified were included. DATA EXTRACTION: The following information was abstracted from published reports (supplemented, in several cases, by the authors): size and type of cohort, mean age, mean duration of follow-up, assay methods, degree of adjustment for confounders, and relationship of CHD risk to the baseline assay results. DATA SYNTHESIS: For fibrinogen, with 4018 CHD cases in 18 studies, comparison of individuals in the top third with those in the bottom third of the baseline measurements yielded a combined risk ratio of 1.8 (95% confidence interval [CI], 1.6-2.0) associated with a difference in long-term usual mean fibrinogen levels of 2.9 pmol/L (0.1 g/dL) between the top and bottom thirds (10.3 vs 7.4 pmol/L [0.35 vs 0.25 g/dL]). For CRP, with 1053 CHD cases in 7 studies, the combined risk ratio of 1.7 (95% CI, 1.4-2.1) was associated with a difference of 1.4 mg/L (2.4 vs 1.0 mg/L). For albumin, with 3770 CHD cases in 8 studies, the combined risk ratio of 1.5 (95% CI, 1.3-1.7) was associated with a difference of 4 g/L (38 vs 42 g/L, ie, an inverse association). For leukocyte count, with 5337 CHD cases in the 7 largest studies, the combined risk ratio of 1.4 (95% CI, 1.3-1.5) was associated with a difference of 2.8 x 10(9)/L (8.4 vs 5.6 x 10(9)/L). Each of these overall results was highly significant (P<.0001). CONCLUSIONS: The published results from these prospective studies are remarkably consistent for each factor, indicating moderate but highly statistically significant associations with CHD. Hence, even though mechanisms that might account for these associations are not clear, further study of the relevance of these factors to the causation of CHD is warranted.

C-Reactive Protein↗
PubMed1998

Is there a link between chronic Helicobacter pylori infection and coronary heart disease?

BACKGROUND: A number of epidemiological studies have reported on associations of coronary heart disease and raised levels of IgG serum antibodies to Helicobacter pylori. There is substantial uncertainty about the interpretation of these reports, however, as some authors have emphasised the most extreme findings to claim that a causal association exists, whereas others have reported the existence of no strong correlations. METHODS: A systematic review of the published literature was conducted. RESULTS: More than twenty relevant epidemiological reports were identified. There was a tendency towards larger odds ratios in smaller case-control studies that recruited controls opportunistically (e.g., hospital inpatients without heart disease) and that did not adjust for many confounders. Overall, the prospective studies reported no strong correlations between coronary heart disease and H. pylori infection. Even in a combined analysis, however, these studies were too small to be able to confirm or refute the existence of weak associations. CONCLUSION: Residual confounding by causal risk factors may well account for the weak associations that have been reported between coronary heart disease and H. pylori.

Antibodies, Bacterial↗
PubMed1998

Persistent infection and vascular disease: a systematic review.

More than 150 epidemiological or clinical studies have reported on associations between vascular disease and the presence of certain persistent bacterial and viral agents, or of clinical conditions (e.g., periodontal disease) that are associated with persistent infection. This article provides a review of such studies, particularly in relation to Helicobacter pylori, Chlamydia pneumoniae, dental disease and cytomegalovirus (CMV), as well as references to possible mechanisms. The association between coronary heart disease and H. pylori or between heart disease and dental disease may be accounted for by residual confounding. Although markers of C. pneumoniae infection are around twenty times more common in atherosclerotic plaques than in disease-free blood vessels, the sequence of infection and disease is uncertain. For CMV, a limited number of patients with classic atherosclerotic coronary heart disease have been investigated in seroepidemiological studies. For all such agents, better and larger seroepidemiological and pathology-based studies are needed to resolve these uncertainties, as well as - at some stage - large-scale, randomised intervention studies.

Journal Article↗