John Danesh

Chronic infections and coronary heart disease: is there a link?

A large number of studies have reported on associations of human coronary heart disease (CHD) and certain persistent bacterial and viral infections. We review the epidemiological and clinical evidence on CHD and Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus (CMV), as well as possible mechanisms. The association between CHD and H pylori may be accounted for by residual confounding from risk factors. Although the association between C pneumoniae and CHD is stronger, the sequence of infection and disease is uncertain. As regards CMV, a limited number of patients with classic atherosclerotic coronary artery disease have been studied. Further studies are needed to resolve these uncertainties.

Lipoprotein(a) and Coronary Heart Disease Meta-Analysis of Prospective Studies

BackgroundStudies of the association between the plasma concentration of lipoprotein(a) [Lp(a)] and coronary heart disease (CHD) have reported apparently conflicting findings. We report a meta-analysis of the prospective studies with at least 1 year of follow-up published before 2000. Methods and ResultsThe following information was abstracted for each study: geographical location of study, size, type of cohort (population-based or selected because of previous disease), mean age, follow-up duration, blood storage temperature and duration, assay methods, degree of adjustment for potential confounders, and relationship of baseline Lp(a) measurement with subsequent CHD risk. There were 5436 deaths from CHD or nonfatal myocardial infarctions during a weighted mean follow-up of 10 years in the 27 eligible studies. Comparison of individuals in the top third of baseline plasma Lp(a) measurements with those in the bottom third in each study yielded a combined risk ratio of 1.6 (95% CI 1.4 to 1.8, 2 P <0.00001), with similar findings when the analyses were restricted to the 18 studies of general populations (combined risk ratio 1.7, 95% CI 1.4 to 1.9; 2 P <0.00001). Despite differences among studies in blood storage techniques and assay methods, there was no significant heterogeneity among the results from the 18 population-based studies or among those from the 9 studies of patients with previous disease. Lp(a) was only weakly correlated with classical vascular risk factors, and adjustment for those that had been recorded made little difference to the reported risk ratios. ConclusionsThese prospective studies demonstrate a clear association between Lp(a) and CHD, but further studies are needed to determine the extent to which this is causal.

Coronary Heart Disease and Iron Status Meta-Analyses of Prospective Studies

BACKGROUNDnStudies 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.nnnMETHODS AND RESULTSnStudies 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).nnnCONCLUSIONSnPublished prospective studies do not provide good evidence to support the existence of strong epidemiological associations between iron status and CHD.

Large-scale evidence that the cardiotoxicity of smoking is not significantly modified by the apolipoprotein E ε2/ε3/ε4 genotype

Summary Results from two small studies, involving a total of only 174 cases, have suggested that the increased risk of coronary heart disease conferred by cigarette smoking is substantially affected by genotype at the apolipoprotein E ( APOE ) e2/e3/e4 polymorphism. We have established APOE genotypes in 4484 patients with acute myocardial infarction diagnosed before the age of 55 years for male and 65 years for female patients, and in 5757 controls with no history of cardiovascular disease. On average, the hazard ratio for myocardial infarction was 1·17 (95% CI 1·09–1·25; p APOE genotypes (χ 2 2 =0·69; p=0·7). When differences in risk between different genotypes are not extreme (as with this APOE polymorphism), reliable assessment of hypothesised gene-environment interactions will often require the study of many thousands of disease cases.

A human germ project

A few weeks ago,Nature reported the sequence of Helicobacter pylori, which is present in up to one in three people and causes peptic ulcers. But many other chronic diseases or cancers are also thought to be caused by infectious agents. Weight is now lent to this theory by two studies that link coronary heart disease to the bacterium Chlamydia pneumoniae, and the implications of these findings are discussed.

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.