R. Philibert, Meeshanthini V Dogan, J. Mills, J. Long
{"title":"AHRR Methylation is a Significant Predictor of Mortality Risk in Framingham Heart Study.","authors":"R. Philibert, Meeshanthini V Dogan, J. Mills, J. Long","doi":"10.17849/insm-48-1-1-11.1","DOIUrl":"https://doi.org/10.17849/insm-48-1-1-11.1","url":null,"abstract":"Background.-The ability to predict mortality is useful to clinicians, policy makers and insurers. At the current time, prediction of future mortality is still an inexact process with some proposing that epigenetic assessments could play a role in improving prognostics. In past work, we and others have shown that DNA methylation status at cg05575921, a well-studied measure of smoking intensity, is also a predictor of mortality. However, the exact extent of that predictive capacity and its independence of other commonly measured mortality risk factors are unknown. Objective.-To determine the capacity of methylation to predict mortality. Method.-We analyzed the relationship of methylation at cg05575921 and cg04987734, a recently described quantitative marker of heavy alcohol consumption, to mortality in the Offspring Cohort of the Framingham Heart Study using proportional hazards survival analysis. Results.-In this group of participants (n = 2278) whose average age was 66 ± 9 years, we found that the inclusion of both cg05575921 and cg04987734 methylation to a base model consisting of age and sex only, or to a model containing 11 commonly used mortality risk factors, improved risk prediction. What is more, prediction accuracy for the base model plus methylation data was increased compared to the base model plus known predictors of mortality (CHD, COPD, or stroke). Conclusion.-Cg05575921, and to a smaller extent cg04987734, are strong predictors of mortality risk in older Americans and that incorporation of DNA methylation assessments to these and other loci may be useful to population scientists, actuaries and policymakers to better understand the relationship of environmental risk factors, such as smoking and drinking, to mortality.","PeriodicalId":39345,"journal":{"name":"Journal of insurance medicine (New York, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47094571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephen A Freitas, Ross MacKenzie, David N Wylde, Jason Von Bergen, J Carl Holowaty, Margaret Beckman, Steven J Rigatti, Daniel Zamarripa, Stacy Gill
{"title":"All-Cause Mortality for Life Insurance Applicants with the Presence of Bundle Branch Block.","authors":"Stephen A Freitas, Ross MacKenzie, David N Wylde, Jason Von Bergen, J Carl Holowaty, Margaret Beckman, Steven J Rigatti, Daniel Zamarripa, Stacy Gill","doi":"10.17849/insm-48-1-1-12.1","DOIUrl":"https://doi.org/10.17849/insm-48-1-1-12.1","url":null,"abstract":"<p><p><b>Objective.-</b>To determine the all-cause mortality of life insurance applicants who have a bundle branch block. <b>Background.-</b>Bundle branch block is an electrocardiographic pattern that has variable prognostic implications. Research studies have shown that both left and right bundle branch block are associated with increased mortality among cases that have heart disease. In the general population and life insurance applicant population, the prevalence of bundle branch block is relatively low, and its effects on long-term prognosis are not as well established. <b>Methodology.-</b>Life insurance applicants with reported bundle branch block were extracted from data covering United States residents between October 2009 and October 2016. Information about these applicants was matched to the Social Security Death Master (SSDMF) file for deaths occurring from 2009 to 2012 and to another commercially available death source file (Other Death Source, ODS) for deaths occurring from 2009 to 2016 to determine vital status. Actual to expected (A/E) mortality ratios were calculated using the Society of Actuaries 2015 Valuation Basic Table (2015VBT), select and ultimate table (age last birthday). All expected bases were not smoker distinct. Confidence bands around these mortality ratios were calculated. The variables of interest were applicant age, gender, location of the bundle branch block, and the presence of cardiac or cardiovascular conditions. <b>Results.-</b>There were 258,529.85 person-years exposure for applicants with bundle branch block. Of the applicants, 57.2% had right bundle branch block. Of person-years exposure, 11.5% had a cardiac condition along with the bundle branch block, and 4.4% had an underlying cardiovascular condition. Female mortality ratios were higher than those for males, but due to the low number of deaths, this difference was not significant. Left bundle branch block mortality ratios (1.01) were 1.4 times higher than those with right (0.74). Those applicants with a cardiac condition along with their bundle branch block had between 1.6 to 1.8 times the mortality ratio depending on the bundle branch block location, and those with a cardiovascular condition had between 1.5 to 1.7 times the mortality ratio over those applicants with just bundle branch block alone. <b>Conclusion.-</b>The presence of bundle branch block in an insurance applicant may be associated with increased all-cause mortality. In this study, life insurance applicants overall had a mortality slightly lower than the expected mortality based on the 2015 VBT. However, applicants with bundle branch block and a cardiac or cardiovascular comorbid condition had a significantly higher mortality ratio.</p>","PeriodicalId":39345,"journal":{"name":"Journal of insurance medicine (New York, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37349134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"JIM Reading List.","authors":"","doi":"10.17849/insm-47-4-1-7.1","DOIUrl":"https://doi.org/10.17849/insm-47-4-1-7.1","url":null,"abstract":"","PeriodicalId":39345,"journal":{"name":"Journal of insurance medicine (New York, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45734819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New Frontier in Lipids: PCSK9 Inhibitors and Implications for the Life Insurance Industry.","authors":"Alacia J Tarpley","doi":"10.17849/insm-47-4-1-6.1","DOIUrl":"https://doi.org/10.17849/insm-47-4-1-6.1","url":null,"abstract":"<p><p>Since the Framingham Heart Study solidified cholesterol as a causative agent in the development of coronary heart disease there has been an explosion of research in the field of lipidology. Many therapeutic options have come and gone as we have been refining the goals of therapy to match the mortality outcome data of large clinical trials. A new frontier has emerged with the introduction of the PCSK9 inhibitors that are able with monthly injections to lower LDL cholesterol >60% with favorable side effect profiles and recently published favorable mortality data. This ushers in a whole new era of cholesterol management. Life insurance medical directors will need to be informed of how these drugs are being used and for conditions such as homozygous hypercholesterolemia, a condition with a very high mortality risk, and for new genetic analysis of affected patients, who are not as rare as once thought. This article provides the background about the development of these drugs, their expanded indications, how they may slip through the cracks of prescription drug (Rx) database inquiries, and touches on therapies in development beyond this class of medications. Medicine is an evolving field. With the new gene editing CRISPR technology it will truly be transformational for these genetically driven conditions with the potential for curative therapy. If curative therapy comes to pass it will, of course, have favorable implications for our evolving life insurance guidelines.</p>","PeriodicalId":39345,"journal":{"name":"Journal of insurance medicine (New York, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36986384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Does an Absent Left Main Lead to a Main Event?","authors":"Sheila MacDonnell, Lisa M Papazian","doi":"10.17849/insm-47-03-184-186.1","DOIUrl":"https://doi.org/10.17849/insm-47-03-184-186.1","url":null,"abstract":"This is a case report of a 29-year-old, male applicant for life insurance who was discovered to have an absence of the left main coronary artery (LMCA), with the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) each arising directly from the left sinus of Valsalva. A brief review of several types of coronary artery anatomic variants will be presented.","PeriodicalId":39345,"journal":{"name":"Journal of insurance medicine (New York, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36471300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Man (or a Woman) is Known by the Company He/She Keeps.","authors":"Rajesh Wadhwa","doi":"10.17849/insm-47-03-141-142.1","DOIUrl":"https://doi.org/10.17849/insm-47-03-141-142.1","url":null,"abstract":"","PeriodicalId":39345,"journal":{"name":"Journal of insurance medicine (New York, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36471737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abnormal Head CT Imaging in Afghanistan: Empiric Treatment of Abnormal Findings in an Austere Environment.","authors":"David S Williams","doi":"10.17849/insm-47-4-1-4.1","DOIUrl":"https://doi.org/10.17849/insm-47-4-1-4.1","url":null,"abstract":"","PeriodicalId":39345,"journal":{"name":"Journal of insurance medicine (New York, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37036725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allan M Andersen, Philip T Ryan, Fredrick X Gibbons, Ronald L Simons, Jeffrey D Long, Robert A Philibert
{"title":"A Droplet Digital PCR Assay for Smoking Predicts All-Cause Mortality.","authors":"Allan M Andersen, Philip T Ryan, Fredrick X Gibbons, Ronald L Simons, Jeffrey D Long, Robert A Philibert","doi":"10.17849/insm-47-4-1-10.1","DOIUrl":"10.17849/insm-47-4-1-10.1","url":null,"abstract":"<p><strong>Objectives: </strong>-Determine whether an epigenetic assay for smoking predicts all-cause mortality in adults participating in a longitudinal study of Iowa adoptees.</p><p><strong>Background: </strong>-Improved biomarkers for smoking are needed given its large public health impact and significant limitations of both self-report and current biomarkers, such as cotinine in detecting smoking. In the past 5 years, multiple epigenome-wide association studies of smoking have identified loci suitable for translation as epigenetic biomarkers for smoking, in particular the CpG cg05575921. Digital polymerase chain reaction methods hold promise for the development of this and other epigenetic biomarkers.</p><p><strong>Methods: </strong>-Participants in the Iowa Adoption Studies were interviewed regarding their smoking habits. DNA was prepared from whole blood and bisulfite-converted for methylation analysis and digital droplet polymerase chain reaction assay of methylation at cg05575921 was performed. National Death Index records were requested for 584 study participants, resulting in 24 complete matches, 210 partial matches and 350 non-matching records. Complete matches were coded as deceased while the remainder were coded as alive (ie, censored). In total, methylation data and vital status information were available for a total of N = 193 subjects, including 15 deceased and 178 non-deceased. Cox regression was used to examine the ability of cg05575921 methylation as a continuous value to predict the timing of mortality with and without the inclusion of age, sex, race, BMI, marital status, educational status, socioeconomic status, cardiovascular risk factors, and a history of cancer as covariates.</p><p><strong>Results: </strong>-Methylation at cg05575921 predicted the hazard of mortality as the sole predictor and after accounting for major demographic and clinical risk factors. The fitted model showed the hazard ratio increased by 3.5% for every 1% decrease in methylation.</p><p><strong>Conclusions: </strong>-Decreased methylation at cg05575921, an emerging epigenetic biomarker for smoking, was associated with early mortality in a longitudinal study of adults after accounting for the impact of major demographic and clinical risk factors for all-cause mortality. This approach may be useful in clinical research or actuarial assessments.</p>","PeriodicalId":39345,"journal":{"name":"Journal of insurance medicine (New York, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518325/pdf/nihms-1628375.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36915820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An Irregular Rhythm with Missing P Waves.","authors":"Ross MacKenzie","doi":"10.17849/insm-47-03-187-190.1","DOIUrl":"https://doi.org/10.17849/insm-47-03-187-190.1","url":null,"abstract":"<p><p>An electrocardiogram on a life insurance applicant with a history of surgically repaired congenital heart disease displays an irregular rhythm with occasional missing P waves.</p>","PeriodicalId":39345,"journal":{"name":"Journal of insurance medicine (New York, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36471296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Takotsubo Syndrome - Case Review.","authors":"Tea Mamaladze","doi":"10.17849/insm-47-03-176-183.1","DOIUrl":"https://doi.org/10.17849/insm-47-03-176-183.1","url":null,"abstract":"","PeriodicalId":39345,"journal":{"name":"Journal of insurance medicine (New York, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36471301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}