Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians

AbstractOBJECTIVESWe sought to prospectively assess whether self-reported periodontal disease is associated with subsequent risk of cardiovascular disease in a large population of male physicians.BACKGROUNDPeriodontal disease, the result of a complex interplay of bacterial infection and chronic inflammation, has been suggested to be a predictor of cardiovascular disease.METHODSPhysicians’ Health Study I was a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 U.S. male physicians. A total of 22,037 physicians provided self-reports of presence or absence of periodontal disease at study entry and were included in this analysis.RESULTSA total of 2,653 physicians reported a personal history of periodontal disease at baseline. During an average of 12.3 years of follow-up, there were 797 nonfatal myocardial infarctions, 631 nonfatal strokes and 614 cardiovascular deaths. Thus, for each end point, the study had >90% power to detect a clinically important increased risk of 50%. In Cox proportional hazards regression analysis adjusted for age and treatment assignment, physicians who reported periodontal disease at baseline had slightly elevated, but statistically nonsignificant, relative risks (RR) of nonfatal myocardial infarction, (RR, 1.12; 95% confidence interval [CI], 0.92 to 1.36), nonfatal stroke (RR, 1.10; CI, 0.88 to 1.37) and cardiovascular death (RR, 1.20; CI, 0.97 to 1.49). Relative risk for a combined end point of all important cardiovascular events (first occurrence of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death) was 1.13 (CI, 0.99 to 1.28). After adjustment for other cardiovascular risk factors, RRs were all attenuated and nonsignificant.CONCLUSIONSThese prospective data suggest that self-reported periodontal disease is not an independent predictor of subsequent cardiovascular disease in middle-aged to elderly men

A prospective study of plasma fish oil levels and incidence of myocardial infarction in U.S. male physicians

AbstractObjectives. This study evaluated whether increased intake of fish oils (eicosapentaenoic and docosahexaenoic acids) might reduce the risk of coronary heart disease.Background.Observational and clinical studies have suggested that increased intake of fish oils, as reflected in plasma levels of fish oils, may reduce the risk of myocardial infarction.Methods.A nested case-control study was conducted among the 14,916 participants in the Physicians' Health Study with a sample of plasma before randomization. Each participant with myocardial infarction occurring during the first 5 years of follow-up was matched by smoking status and age with a randomly chosen control participant who had not developed coronary heart disease.Results.Mean levels of fish oils (with 95% confidence interval [CI] for paired differences and p values) in case and control participants, expressed as present of total fatty acids, were, for eicosapentaenoic acid, 0.26 versus 0.25 (95% CI - 0.03 to 0.05, p = 0.70) in cholesterol esters and 0.56 versus 0.54 (95% CI -0.04 to 0.09, p = 0.44) in phospholipids, and for docosahexaenoic acid, 0.23 versus 0.24 (95% CI -0.07 to 0.04, p = 0.64) in cholesterol esters and 2.22 versus 2.14 (95% CI -0.10 to 0.27, p = 0.36) in phospholipids. Results adjusted for major cardiovascular risk factors showed a very similar lack of association between fish oil levels and the incidence of myocardial infarction.Conclusions.These results indicate no beneficial effect of increased fish oil consumption on the incidence of a first myocardial infarction. However, the effect of very high levels of fish oils could not be evaluated

Social Determinants and the Classification of Disease: Descriptive Epidemiology of Selected Socially Mediated Disease Constellations

Background Most major diseases have important social determinants. In this context, classification of disease based on etiologic or anatomic criteria may be neither mutually exclusive nor optimal. Methods and Findings Units of analysis comprised large metropolitan central and fringe metropolitan counties with reliable mortality rates – (n = 416). Participants included infants and adults ages 25 to 64 years with selected causes of death (1999 to 2006). Exposures included that residential segregation and race-specific social deprivation variables. Main outcome measures were obtained via principal components analyses with an orthogonal rotation to identify a common factor. To discern whether the common factor was socially mediated, negative binomial multiple regression models were developed for which the dependent variable was the common factor. Results showed that infant deaths, mortality from assault, and malignant neoplasm of the trachea, bronchus and lung formed a common factor for race-gender groups (black/white and men/women). Regression analyses showed statistically significant, positive associations between low socio-economic status for all race-gender groups and this common factor. Conclusions Between 1999 and 2006, deaths classified as “assault” and “lung cancer”, as well as “infant mortality” formed a socially mediated factor detectable in population but not individual data. Despite limitations related to death certificate data, the results contribute important information to the formulation of several hypotheses: (a) disease classifications based on anatomic or etiologic criteria fail to account for social determinants; (b) social forces produce demographically and possibly geographically distinct population-based disease constellations; and (c) the individual components of population-based disease constellations (e.g., lung cancer) are phenotypically comparable from one population to another but genotypically different, in part, because of socially mediated epigenetic variations. Additional research may produce new taxonomies that unify social determinants with anatomic and/or etiologic determinants. This may lead to improved medical management of individuals and populations

Light-to-moderate alcohol consumption and mortality in the physicians’ health study enrollment cohort

AbstractOBJECTIVESThis study examined the relationship between light-to-moderate alcohol consumption and cause-specific mortality.BACKGROUNDPrevious studies suggest a J-shaped relation between alcohol and total mortality in men. A decrease in cardiovascular disease (CVD) mortality without a significant increase in other causes of mortality may explain the overall risk reduction at light-to-moderate levels.METHODSWe conducted a prospective cohort study of 89,299 U.S. men from the Physicians’ Health Study enrollment cohort who were 40 to 84 years old in 1982 and free of known myocardial infarction, stroke, cancer or liver disease at baseline. Usual alcohol consumption was estimated by a limited food frequency questionnaire.RESULTSThere were 3,216 deaths over 5.5 years of follow-up. We observed a U-shaped relationship between alcohol consumption and total mortality. Compared with rarely/never drinkers, consumers of 1, 2 to 4 and 5 to 6 drinks per week and 1 drink per day had significant reductions in risk of death (multivariate relative risks [RRs] of 0.74, 0.77, 0.78 and 0.82, respectively) with no overall benefit or harm detected at the ≥2 drinks per day level (RR = 0.95; 95% confidence interval (CI), 0.79 to 1.14). The relationship with CVD mortality was inverse or L-shaped with apparent risk reductions even in the highest category of ≥2 drinks per day (RR = 0.76; 95% CI, 0.57 to 1.01). We found no clear harm or benefit for total or common site-specific cancers. For remaining other cancers, there was a nonsignificant 28% increased risk for those consuming ≥2 drinks per day.CONCLUSIONSThese data support a U-shaped relation between alcohol and total mortality among light-to-moderate drinking men. The U-shaped curve may reflect an inverse association for CVD mortality, no association for common site-specific cancers and a possible positive association for less common cancers

Lack of validity of self-reported mammography data

This qualitative literature review aimed to describe the totality of peer-reviewed scientific evidence from 1990 to 2017 concerning validity of self-reported mammography. This review included articles about mammography containing the words accuracy, validity, specificity, sensitivity, reliability or reproducibility; titles containing self-report, recall or patient reports, and breast or ‘mammo’; and references of identified citations focusing on evaluation of 2-year self-reports. Of 45 publications meeting the eligibility criteria, 2 conducted in 1993 and 1995 at health maintenance organisations in Western USA which primarily served highly educated whites provided support for self-reports of mammography over 2 years. Methodological concerns about validity of self-reports included (1) telescoping, (2) biased overestimates particularly among black women, (3) failure to distinguish screening and diagnostic mammography, and (4) failure to address episodic versus consistent mammography use. The current totality of evidence supports the need for research to reconsider the validity of self-reported mammography data as well as the feasibility of alternative surveillance data sources to achieve the goals of the Healthy People Initiative

Antipsychotic Drug Therapies: Matching primary care practice to clinical challenges

Primary health care providers prescribe over 50 percent of drug therapies for patients with mental health issues in the United States. Nonetheless, primary health care providers tend to be reluctant to prescribe antipsychotic drug therapies despite their widespread availability and favorable benefit-to-risk ratio. This may be due, at least in part, to appropriate concerns about the serious adverse effects of all earlier first generation, or typical, as well as many of the earlier second generation, or atypical, antipsychotic drug therapies

The data monitoring experience in the Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) program.

BACKGROUND: The CHARM program was designed as 3 separate randomized trials comparing candesartan with placebo in patients with chronic heart failure (CHF) who (1) were intolerant to angiotensin-converting enzyme inhibitor and had left ventricular ejection fraction (LVEF) 0.40. CHARM provides an interesting example of the challenges faced by a Data and Safety Monitoring Committee (DSMC). METHODS: Although the primary efficacy end point for each component trial was cardiovascular (CV) death or hospitalization for CHF, the primary outcome for the overall program was all-cause mortality. The DSMC received monthly safety reports and also met every 6 months (7 times in all) to review interim reports. Statistical stopping guidelines were predefined for all-cause mortality in the overall program. The overarching principle of the DSMC was proof beyond a reasonable doubt that would be likely to influence clinical practice. RESULTS: There were significant treatment differences in all-cause mortality for the overall program at several interim analyses, and the statistical stopping guideline was reached on one occasion. However, even a conventional level of statistical significance (P < .050) was achieved in only 1 of the 3 component trials. The DSMC consistently recommended that the program continue as planned. The final published result for all-cause death over a median of 3.1 years was a 9% reduction in hazard (95% CI 0%-17%, P = .055), whereas for CV death or hospitalization for CHF, there was a 16% reduction in hazard (95% CI 9%-23%, P < .0001). Subsequent exploratory analyses suggest that the hazard reduction in CV death was more marked in the first year after randomization and that, if real, this apparent treatment-time interaction offers a plausible explanation for why the interim mortality data showed statistically more extreme findings than the overall final results. CONCLUSION: The DSMC experience in the CHARM program illustrates the importance of continuing a trial to its scheduled completion unless there is proof beyond a reasonable doubt that would influence clinical practice rather than strict reliance on a statistical stopping guideline