Abstract MP033: Socioeconomic Disparities in the Risk of Developing Heart Failure: Prospective Findings from the Moli-Sani Study

Introduction: The association between socioeconomic status (SES) and the risk of cardiovascular disease and all-cause mortality is well-established, while the impact of SES on heart failure (HF) incidence is less explored. Hypothesis: We tested the hypothesis of a SES gradient in the risk of HF. Methods: Population-based cohort study on 22,395 individuals (mean age 55.3±11.7, 47.7% men) free from HF at baseline randomly recruited from the general population included in the Moli-sani study (Italy). The cohort was followed up for a median of 7.6 years (168,031 person-years). Annual household income (Euros) and educational level were used as SES indicators. Presence of risk factors at baseline and a panel of health behaviours were tested as possible mediators of the association between SES and incident HF. Incident HF at follow-up was defined by HF hospitalization or HF death, according to the International Classification of Diseases-Ninth Revision (ICD-9). Hazard ratios (HR) with 95% confidence intervals were calculated by Cox-proportional hazard models. Results: We identified 757 first HF events. Both lowest education (middle and secondary schools) and household income (<60,000 Euros/y) were separately associated with increased risk of HF as compared with the highest category (Table). After simultaneous adjustment, the association of income appeared to be largely explained by education. The inclusion of traditional risk factors, biomarkers of heart failure and health-behaviors into the model attenuated the association of low education with HF incidence by 12%, 3.8% and 11.5%, respectively. Overall, the full explanatory model accounted for 23.8% of the educational gradient in the risk of HF (Table). Conclusions: Educational level, rather than income, is an independent predictor of HF development. Excess risk associated with low education was partially explained by traditional health risk factors, biomarkers of subclinical damage and health-behaviors.

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Prevalence and Predictors of Non-Adherence to 6-Mercaptopurine (6MP) in Children with Acute Lymphoblastic Leukemia (ALL) - a Children’s Oncology Group Study.

Blood ◽

10.1182/blood.v112.11.897.897 ◽

2008 ◽

Vol 112 (11) ◽

pp. 897-897

Author(s):

Smita Bhatia ◽

Doojduen Villaluna ◽

Wendy Landier ◽

Alexandra Schaible ◽

Lindsey Hageman ◽

...

Keyword(s):

High School ◽

Household Income ◽

Lymphoblastic Leukemia ◽

Systemic Exposure ◽

Small Sample ◽

Future Research ◽

Annual Household Income ◽

Increased Risk ◽

The Mean ◽

The Impact

Abstract Use of contemporary risk-based therapy in children with ALL has resulted in five-year survival rates exceeding 80%. Achievement of durable remissions requires a maintenance phase composed of oral administration of antimetabolites (6-mercaptopurine and methotrexate) for approximately two years. Previous studies have shown that low systemic exposure to oral 6MP adversely affects prognosis, thus emphasizing the critical need for therapeutic levels throughout maintenance. However, significant inter-patient variability in red cell thioguanine nucleotide (6TGN – a major metabolite of 6MP) concentrations exists, and could in part be related to failure to adhere to prescribed therapy. Non-adherence in pediatric ALL patients has been reported – however, small sample sizes and varying methods of assessment make it difficult to understand the magnitude of this problem. The purpose of our study was to describe adherence to oral 6MP in a large multi-ethnic cohort of children with ALL. Patients were eligible to participate if they were diagnosed with ALL at age less than 22 years, belonged to one of four ethnic/racial groups (Asian, African-American, Caucasian, or Hispanic), and had completed at least 24 weeks of maintenance therapy. We have restricted the current report to Caucasians, where we have completed our target accrual. To measure 6MP adherence, we used the Medication Event Management System (MEMS) and supplied each patient with a MEMS TrackCap. This electronic cap allowed the collection of real-time data by recording the date and time(s) when the 6MP bottle was opened over a 6-month period. The MEMS data was downloaded at the end of the 6-month study period. Patients/parents also completed a self-administered sociodemographic questionnaire. Longitudinal analysis was performed using the Generalized Estimating Equations. A total of 173 Caucasian patients provided 26,424 person-days of observation for 6MP adherence. The median age at diagnosis was 5 years (1 to 19), and at study participation was 6 years (range, 2 to 20); median time from diagnosis was 18.8 months, and from start of maintenance, 8.1 months; 67% were males. NCI criteria for high-risk disease were present in 42% of the patients. The median annual household income was between $50K and $75K; 79% of the mothers and 72% of the fathers had received education beyond high school. The median number of household members (including patient) was 4 (range, 2 to 10). Adherence was defined as the ratio of 6MP bottle openings to actual 6MP doses prescribed, calculated as a percentage (“percent adherence”). Prescribed doses for the entire 6-month period were reviewed for each patient, and instances when 6MP was withheld by the prescriber due to toxicity or illness were taken into account for purposes of calculating adherence. The mean percent adherence over the 6-month study period was 85% (range 11% to 100%). The mean monthly percent adherence declined significantly over the 6-month study period (p=0.002). Multivariate analysis identified certain subgroups that were at increased risk of lower percent adherence (Figure): age >8 years at study entry (p=0.01); households that included members other than the mother, father, and patient (<0.001); father’s education ≤ high school or ≥ college degree (p=0.05), and annual household income <$20k or ≥ $100K (p=.045). In this study, 19% of the study participants were <80% adherent at the end of the first study month; this increased to 30% by the end of the 6-month study period. Over 6% of patients were <50% adherent at the end of the first month, and this increased to 11% at month 6 – demonstrating that over 10% of the patients were taking less than 50% of their prescribed doses of 6MP. This study demonstrates that non-adherence to 6MP is prevalent in children undergoing treatment for ALL and increases with time on maintenance. It further delineates certain sociodemographic variables that define those at highest risk for non-adherence. Patients from this study will be followed long-term to understand the impact of non-adherence on outcome. Future research needs to focus on developing targeted, multidisciplinary interventions to reduce non-adherence to therapy. Figure Figure

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Predictors of episodic migraine transformation to chronic migraine: A systematic review and meta-analysis of observational cohort studies

Cephalalgia ◽

10.1177/0333102419883355 ◽

2019 ◽

Vol 40 (5) ◽

pp. 503-516 ◽

Cited By ~ 5

Author(s):

Jingjing Xu ◽

Fanyi Kong ◽

Dawn C Buse

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Cohort Studies ◽

Chronic Migraine ◽

Risk Ratio ◽

Household Income ◽

Meta Analysis ◽

Episodic Migraine ◽

Annual Household Income ◽

Increased Risk

Background and purpose An estimated 2.5–3.1% of people with episodic migraine develop chronic migraine in a year. Several risk factors are associated with an increased risk for this transformation. We conducted a systematic review and meta-analysis to provide quantitative and qualitative data on predictors of this transformation. Methods An electronic search was conducted for published, prospective, cohort studies that reported risk factors for chronic migraine among people with episodic migraine. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. Quality of evidence was determined according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Effect estimates were retrieved and summarized using risk ratios. Results Of 5695 identified publications, 11 were eligible for inclusion. The pooled analysis (GRADE system) found “high” evidence for monthly headache day frequency ≥ 10 (risk ratio = 5.95), “moderate” evidence for depression (risk ratio = 1.58), monthly headache day frequency ≥ 5 (risk ratio = 3.18), and annual household income ≥ $50,000 (risk ratio = 0.65) and “very low” evidence for allodynia (risk ratio = 1.40) and medication overuse (risk ratio = 8.82) in predicting progression to chronic migraine. Conclusions High frequency episodic migraine and depression have high quality evidence as predictors of the transformation from episodic migraine to chronic migraine, while annual household income over $50,000 may be protective.

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The Impact of Transitions of Care Pharmacist Services and Identification of Risk Predictors in Heart Failure Readmission

Journal of Pharmacy Practice ◽

10.1177/0897190019884173 ◽

2019 ◽

pp. 089719001988417 ◽

Cited By ~ 2

Author(s):

Marci Wood ◽

Tracey Sweeney ◽

Molly Trayah ◽

Maria Civalier ◽

Wesley McMillian

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Angiotensin Receptor Blockers ◽

Significant Risk ◽

Retrospective Chart Review ◽

Transitions Of Care ◽

Converting Enzyme Inhibitors ◽

Increased Risk ◽

Risk Predictors ◽

The Impact

Background: Heart failure (HF) is a prevalent and costly disease state for adult Americans, with 30-day readmissions rates for patients with HF utilized to limit hospital compensation. Objective: To determine the impact of the transitions of care (TOC) service at our institution on 30-day all-cause and HF readmissions and identify predictive risk factors for 30-day all-cause readmission. Methods: Retrospective chart review of patients aged 18 years and older admitted with HF and all subsequent readmissions between October 1, 2015, and September 30, 2017. A weighted logistic regression model was developed to determine risk factors for 30-day all-cause readmission. Results: There were no significant differences in all-cause or HF readmission rates analyzed by TOC service involvement. Significant risk predictors for 30-day all-cause readmission included discharge to a rehabilitation facility (odds ratio [OR] = 9.3) or home with home health (OR = 1.6) versus home with self-care. Comorbidities associated with an increased risk of 30-day all-cause readmission included diabetes, coronary artery disease, and aortic stenosis. Use of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and spironolactone was associated with decreased risk of 30-day all-cause readmission. Conclusion: Identified predictors in the patient population with HF at our institution may be used to target patients at increased risk of all-cause readmission within 30 days.

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Abstract 078: Total Brachial Artery Reactivity And Incident Heart Failure And Heart Failure Sub-types: Multi-ethnic Study Of Atherosclerosis

Circulation ◽

10.1161/circ.143.suppl_1.078 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Daniela Charry

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Endothelial Dysfunction ◽

Ejection Fraction ◽

Brachial Artery ◽

Minimum Diameter ◽

Ethnic Study ◽

Increased Risk ◽

The Impact ◽

Brachial Artery Reactivity

Introduction: Endothelial dysfunction may be a phenotypic expression of heart failure (HF). Total brachial artery reactivity (TBAR) is a non-invasive measurement of endothelial function that has been associated with increased risk of cardiovascular outcomes. Limited information is currently available on the impact of TBAR on incident HF and its subtypes. The aim of this study was to evaluate whether TBAR is associated with incident HF, HF with reduced ejection fraction (HFrEF), or HF with preserved ejection fraction (HFpEF) in a community-based study. Hypothesis: We hypothesized that TBAR would be inversely related with incident HF and both HF subtypes. Methods: Sample included 5,499 participants (45-84 years of age) from the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease at baseline. Brachial artery ultrasound was performed after five minutes of cuff occlusion at the right forearm. TBAR was calculated as the difference between maximum and minimum brachial artery diameters following cuff release, divided by the minimum diameter multiplied by 100%. A dichotomous TBAR variable was created based on the median value (below or above 7.9%). Participants with EF ≤ 40% were considered HFrEF and those with EF ≥ 50% were considered HFpEF. Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals. Results: Over a mean follow-up period of 12.5 years, incident HF was diagnosed in 250 participants; 106 classified as HFpEF, 98 as HFrEF, and 46 with unknown or borderline EF (41-49%). Crude analysis revealed that those with TBAR below the median have significantly higher risk of HF (HR 1.46; 95% CI 1.13-1.88, p<0.01) and HFrEF (HR 1.61; 95% CI 1.07-2.43, p<0.05). Following adjustment for known HF risk factors (e.g. age, gender, race, blood pressure, others), these relationships were no longer statistically significant. Borderline significant results were revealed in those with HFpEF (HR 1.43; 95% CI 0.97-2.12, p=0.06). Kaplan-Meier curves suggest significantly lower risks of developing HF and HFrEF in those with TBAR above the median (log-rank p<0.05 for both). When examined as a continuous variable, with a cut point of 50% for EF, every 1-standard deviation (9.7%) increase in TBAR resulted in a 19% and 29% decrease in risk of HF (p<0.05) and HFrEF (p=0.05), respectively. Conclusions: Lower TBAR values were associated with higher rates of incident HF and HFrEF, suggesting a possible role of endothelial dysfunction in HF pathogenesis. The impact of other known HF risk factors may mediate this relationship, thus further research is warranted.

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Mortality risk factors and survival of colon cancer patient.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14653 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14653-e14653

Author(s):

Runhua Shi ◽

Manga Devi Kodali ◽

Stephani Chang Wang ◽

Kalyana C Lavu ◽

Lihong Liu ◽

...

Keyword(s):

Risk Factors ◽

Colon Cancer ◽

Cancer Patients ◽

Household Income ◽

Cancer Survival ◽

Rank Test ◽

Annual Household Income ◽

Life Styles ◽

Increased Risk ◽

History Of

e14653 Background: It is estimated that 142,820 people will be diagnosed and 50,830 will die from colon cancer in U.S. in 2013. The known risk factors include age (>50 years old), personal history of colon polyp(s) and Inflammatory bowel disease, family history of colon cancer, hereditary syndromes, Black race, type II Diabetes Mellitus, obesity, physical inactivity, smoking and alcohol use. In order to improve colon cancer survivorship, current study explores factors that affect it. Methods: Data of 524,613 colon cancer patients between 1973 and 2009 was obtained from the Surveillance Epidemiology and End Results (SEER) program. Factors evaluated in this study were age at diagnosis, gender, race, annual household income, education, unemployment, and smoking. Clinical factors evaluated include SEER historic stage and treatments received. The definition of these factors was based on the SEER data dictionary. Kaplan-Meier method and log rank test was used to estimate and compare survivals. Cox regressions were used to identify risk factors that affect survival. Results: Characteristics of this half millions colon cancer patients were 51.3% of males, 84.4% of whites, and 70% of adjusted household income <$50,000. Primary site: Sigmoid Colon (30.84%), Cecum (22.7%), Ascending Colon (9.42%), and others (9.42%). Stage: Localized (37%), Regional (36.26%), Distant (20.01%), and Unstaged (6.63%). In multivariate analysis, adjusting for other factors, age (≤49 vs. 60-69, HR=0.57), female gender (HR=0.87), stage (localized vs. distant stage, HR= 0.15) and race (Black HR=1.38, vs. Asian) are significant factors in colon cancer survival. People living in areas with a high percentage of smokers have increased risk by 8%. People living in areas of higher unemployment have 6% increased risk. Household income and education level have relatively less effect on colon cancer survival (40-55k vs. 0-40k, HR=1.02). Conclusions: We conclude that in a large database, age, race, stage, smoking, and unemployment have significant impact on colon cancer survival. Other factors such as insurance status, detailed treatments, screening effect, individual life styles and etc. need further investigation.

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The impact of global and local Polynesian genetic ancestry on complex traits in Native Hawaiians

PLoS Genetics ◽

10.1371/journal.pgen.1009273 ◽

2021 ◽

Vol 17 (2) ◽

pp. e1009273

Author(s):

Hanxiao Sun ◽

Meng Lin ◽

Emily M. Russell ◽

Ryan L. Minster ◽

Tsz Fung Chan ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Type 2 Diabetes ◽

Snp Array ◽

Small Sample ◽

Genetic Ancestry ◽

Native Hawaiians ◽

Increased Risk ◽

The Impact

Epidemiological studies of obesity, Type-2 diabetes (T2D), cardiovascular diseases and several common cancers have revealed an increased risk in Native Hawaiians compared to European- or Asian-Americans living in the Hawaiian islands. However, there remains a gap in our understanding of the genetic factors that affect the health of Native Hawaiians. To fill this gap, we studied the genetic risk factors at both the chromosomal and sub-chromosomal scales using genome-wide SNP array data on ~4,000 Native Hawaiians from the Multiethnic Cohort. We estimated the genomic proportion of Native Hawaiian ancestry (“global ancestry,” which we presumed to be Polynesian in origin), as well as this ancestral component along each chromosome (“local ancestry”) and tested their respective association with binary and quantitative cardiometabolic traits. After attempting to adjust for non-genetic covariates evaluated through questionnaires, we found that per 10% increase in global Polynesian genetic ancestry, there is a respective 8.6%, and 11.0% increase in the odds of being diabetic (P = 1.65×10−4) and having heart failure (P = 2.18×10−4), as well as a 0.059 s.d. increase in BMI (P = 1.04×10−10). When testing the association of local Polynesian ancestry with risk of disease or biomarkers, we identified a chr6 region associated with T2D. This association was driven by an uniquely prevalent variant in Polynesian ancestry individuals. However, we could not replicate this finding in an independent Polynesian cohort from Samoa due to the small sample size of the replication cohort. In conclusion, we showed that Polynesian ancestry, which likely capture both genetic and lifestyle risk factors, is associated with an increased risk of obesity, Type-2 diabetes, and heart failure, and that larger cohorts of Polynesian ancestry individuals will be needed to replicate the putative association on chr6 with T2D.

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Associations between left bundle branch block with different PR intervals, QRS durations, heart rates and the risk of heart failure: a register-based cohort study using ECG data from the primary care setting

Open Heart ◽

10.1136/openhrt-2020-001425 ◽

2021 ◽

Vol 8 (1) ◽

pp. e001425

Author(s):

Marc Meller Søndergaard ◽

Johannes Riis ◽

Karoline Willum Bodker ◽

Steen Møller Hansen ◽

Jesper Nielsen ◽

...

Keyword(s):

Heart Failure ◽

Primary Care ◽

Heart Rate ◽

Left Bundle Branch Block ◽

Bundle Branch Block ◽

Increased Risk ◽

Pr Interval ◽

Qrs Duration ◽

The Impact

AimLeft bundle branch block (LBBB) is associated with an increased risk of heart failure (HF). We assessed the impact of common ECG parameters on this association using large-scale data.Methods and resultsUsing ECGs recorded in a large primary care population from 2001 to 2011, we identified HF-naive patients with a first-time LBBB ECG. We obtained information on sex, age, emigration, medication, diseases and death from Danish registries. We investigated the association between the PR interval, QRS duration, and heart rate and the risk of HF over a 2-year follow-up period using Cox regression analysis.Of 2471 included patients with LBBB, 464 (18.8%) developed HF during follow-up. A significant interaction was found between QRS duration and heart rate (p<0.01), and the analyses were stratified on these parameters. Using a QRS duration <150 ms and a heart rate <70 beats per minute (bpm) as the reference, all groups were statistically significantly associated with the development of HF. Patients with a QRS duration ≥150 ms and heart rate ≥70 bpm had the highest risk of developing HF (HR 3.17 (95% CI 2.41 to 4.18, p<0.001). There was no association between the PR interval and HF after adjustment.ConclusionProlonged QRS duration and higher heart rate were associated with increased risk of HF among primary care patients with LBBB, while no association was observed with PR interval. Patients with LBBB with both a prolonged QRS duration (≥150 ms) and higher heart rate (≥70 bpm) have the highest risk of developing HF.

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Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽

10.1161/str.45.suppl_1.tp136 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

George Howard ◽

Mary Cushman ◽

Maciej Banach ◽

Brett M Kissela ◽

David C Goff ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Stroke Risk ◽

Multivariable Analysis ◽

The Elderly ◽

Stroke Risk Factors ◽

Age Related ◽

Increased Risk ◽

The Impact ◽

Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

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Abstract 1122‐000035: Is Age Critical in Determining Stroke Severity Within the Telestroke Network?

Stroke: Vascular and Interventional Neurology ◽

10.1161/svin.01.suppl_1.000035 ◽

2021 ◽

Vol 1 (S1) ◽

Author(s):

Cassie A Simmons ◽

Nicolas Poupore ◽

Fernando Gonzalez ◽

Thomas I Nathaniel

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Risk Factor ◽

Univariate Analysis ◽

Baseline Risk ◽

Stroke Severity ◽

Stroke Patients ◽

Stroke Risk Factor ◽

Patients Âgés ◽

Increased Risk

Introduction : Age is the single most important risk factor for stroke and an estimated 75% of all strokes occur in people >65 years of age. In addition, adults >75 years’ experience more hospitalization stays and higher mortality rates with an estimated 50% in the occurrence of all strokes. Several comorbidities have been linked to an increased risk and severity of acute ischemic stroke (AIS). How these factors differentially contribute to the severity of stroke in patients ages >65 and <75 as well as those ≥75 is not known. In this study, we aim to investigate how age, coupled with various clinical risk factors, affects AIS severity within these two age categories. Methods : This retrospective data analysis study was conducted using the data collected from the PRISMA Health Stroke Registry between 2010 and 2016. Baseline clinical and demographic data for patients ages >65 and <75 as well as those ≥75 was analyzed using univariate analysis. Receiver operating characteristic (ROC) curve analysis and multivariate regression models were used to examine the association of specific baseline risk factors or comorbidities associated with worsening or improving neurologic functions. The primary functions were risk factors associated with improving or worsening neurologic outcome in each age category. Results : Adjusted multivariate analysis showed that AIS population of patients >65 and <75 experiencing heart failure (OR = 4.398, 95% CI, 3.912 – 494.613, P = 0.002) and elevated HDL levels (OR = 1.066, 95% CI, 1.009 – 1.126, P = 0.024) trended towards worsening neurologic functions while patients experiencing obesity (OR = 0.177, 95% CI, 0.041 – 0.760, P = 0.020) exhibited improving neurologic functions. For the patients ≥75 years of age, direct admission (OR = 0.270, 95% CI, 0.085 – 0.856, P = 0.026) was associated with improvement of patients treated in the telestroke. Conclusions : Age is a strong risk factor for AIS, and aged stroke patients have higher morbidity and worsening functional recovery than younger patients. In this study, we observed differences in stroke risk factor profiles for >65 and <75 and ≥75 age categories. Heart failure and elevated HDL levels were significantly associated with worsening neurologic functions among AIS for patients aged >65 and <75. Obese patients and individuals ≥75 years who were directly admitted were most likely to exhibit improving neurologic functions. Most importantly, findings from this study reveal specific risk factors that can be managed to improve the care in older stroke patients treated in the telestroke network.

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Abstract P253: Proton Pump Inhibitor Use is Positively Associated with Incidence of Cardiovascular Disease

Circulation ◽

10.1161/circ.135.suppl_1.p253 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Elizabeth J Bell ◽

Jennifer L St. Sauver ◽

Veronique L Roger ◽

Nicholas B Larson ◽

Hongfang Liu ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Coronary Heart Disease ◽

Heart Disease ◽

Language Processing ◽

Proton Pump ◽

Hazard Ratio ◽

Time Varying ◽

Increased Risk ◽

The Impact

Introduction: Proton pump inhibitors (PPIs) are used by an estimated 29 million Americans. PPIs increase the levels of asymmetrical dimethylarginine, a known risk factor for cardiovascular disease (CVD). Data from a select population of patients with CVD suggest that PPI use is associated with an increased risk of stroke, heart failure, and coronary heart disease. The impact of PPI use on incident CVD is largely unknown in the general population. Hypothesis: We hypothesized that PPI users have a higher risk of incident total CVD, coronary heart disease, stroke, and heart failure compared to nonusers. To demonstrate specificity of association, we additionally hypothesized that there is not an association between use of H 2 -blockers - another commonly used class of medications with similar indications as PPIs - and CVD. Methods: We used the Rochester Epidemiology Project’s medical records-linkage system to identify all residents of Olmsted County, MN on our baseline date of January 1, 2004 (N=140217). We excluded persons who did not grant permission for their records to be used for research, were <18 years old, had a history of CVD, had missing data for any variable included in our model, or had evidence of PPI use within the previous year.We followed our final cohort (N=58175) for up to 12 years. The administrative censoring date for CVD was 1/20/2014, for coronary heart disease was 8/3/2016, for stroke was 9/9/2016, and for heart failure was 1/20/2014. Time-varying PPI ever-use was ascertained using 1) natural language processing to capture unstructured text from the electronic health record, and 2) outpatient prescriptions. An incident CVD event was defined as the first occurrence of 1) validated heart failure, 2) validated coronary heart disease, or 3) stroke, defined using diagnostic codes only. As a secondary analysis, we calculated the association between time-varying H 2 -blocker ever-use and CVD among persons not using H 2 -blockers at baseline. Results: After adjustment for age, sex, race, education, hypertension, hyperlipidemia, diabetes, and body-mass-index, PPI use was associated with an approximately 50% higher risk of CVD (hazard ratio [95% CI]: 1.51 [1.37-1.67]; 2187 CVD events), stroke (hazard ratio [95% CI]: 1.49 [1.35-1.65]; 1928 stroke events), and heart failure (hazard ratio [95% CI]: 1.56 [1.23-1.97]; 353 heart failure events) compared to nonusers. Users of PPIs had a 35% greater risk of coronary heart disease than nonusers (95% CI: 1.13-1.61; 626 coronary heart disease events). Use of H 2 -blockers was also associated with a higher risk of CVD (adjusted hazard ratio [95% CI]: 1.23 [1.08-1.41]; 2331 CVD events). Conclusions: PPI use is associated with a higher risk of CVD, coronary heart disease, stroke and heart failure. Use of a drug with no known cardiac toxicity - H 2 -blockers - was also associated with a greater risk of CVD, warranting further study.

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