Host Genetics and Risk of Cardiovascular Disease in a Prospective Cohort of Adult Non-Hodgkin Lymphoma Survivors

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1573-1573
Author(s):  
Carrie A. Thompson ◽  
Thomas M Habermann ◽  
Matthew J Maurer ◽  
Cristine Allmer ◽  
Susan L Slager ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Heart Disease ◽  
Medical Records ◽  
Minor Allele ◽  
Newly Diagnosed ◽  
Cvd Risk ◽  
Non Hodgkin Lymphoma ◽  
A Minor

Abstract Abstract 1573 Background. Treatment of non-Hodgkin lymphoma (NHL) can lead to the development of cardiovascular disease (CVD). In a previous report, we found that the risk of CVD in patients with NHL diagnosed in the recent treatment era (since 2002) was approximately 1% per year after the initial diagnosis of lymphoma. We evaluated the association of 30 candidate single nucleotide polymorphisms (SNPs) in genes associated with anthracycline-induced cardiotoxicity in children (SLC10A2, SLC28A3, ABCC1, ABCB3, CBR3, FMO2, SPG7) and genes associated with venous thromboembolism (VTE) in adults (ABO, F2/CKPA5, F5, F11, KLKB1, SCUBE1, SLC19A, SELP) with the risk of new onset cardiovascular disease in a cohort of NHL patients. Methods. All patients were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE, and were enrolled from 2002–2008. The MER offers enrollment to all consecutive patients with newly diagnosed NHL who are US residents and age >18 years. Clinical data from the time of diagnosis and treatment data are abstracted from medical records using a standard protocol. Patients are prospectively contacted via telephone or in person per protocol every 6 months for the first 3 years from diagnosis and yearly afterwards to assess disease status and development of comorbid conditions. CVD events, including heart failure (HF), myocardial infarction (MI), arrhythmia, pericarditis, and valvular heart disease, occurring after diagnosis were identified during follow-up and validated against medical records. HF was validated with the Cardiovascular Health Study Criteria and/or the Framingham Criteria. MI was validated using case definition standards of coronary heart disease, while arrhythmia, pericarditis, and valvular heart disease were validated using clinical definitions. Genotyping was conducted using a custom Illumina iSelect platform. Cox regression was used to estimate Hazard Ratios (HRs) and 95% confidence intervals (CI) for individual SNPs with time to CVD, with death modeled as a competing risk. Each SNP was modeled with the most prevalent homozygous genotype used as the reference group, and each SNP was modeled as having a log-additive (per minor allele) effect in the regression model. An ordinal test was used to assess the trend, and p<0.05 was considered statistically significant. Results. There were 805 newly diagnosed NHL patients with no history of CVD at time of lymphoma diagnosis and had genotype data available for analysis. The median age at diagnosis was 61 years (range, 21–93) and 53% were male. The most common subtypes were follicular lymphoma (33%), diffuse large B-cell lymphoma (29%), and marginal zone lymphoma (14%). Anthracycline-based chemotherapy as initial therapy or at re-treatment was used in 51% of the patients and radiation therapy was used in 18%. Median follow-up of all cases was 59 months (range, 1–105). There were 36 incident CVD events (4.5%) and 139 deaths (17%). The most common CVD events were arrhythmia (N=17) and heart failure (N=14). There was no association with any of the anthracycline-induced cardiotoxicity genes and risk of CVD overall or in the subgroup of patients (N=406) who received an anthracycline. Of the venous thromboembolism (VTE) SNPs, rs4253399 in F11 (coagulation factor 11) with a minor allele frequency of 0.39 was associated with risk of CVD (HR=2.14; 95%CI 1.35–3.40; p=0.001). When restricted to anthracycline-treated patients, the HR for rs4253399 became stronger (HR=2.56; 95%CI 1.39–4.72; p=0.003), and an ABOSNP (rs660340) with a minor allele frequency of 0.43 became significant (HR=2.14; 95%CI 1.13–4.04; p=0.02). Conclusions. This is the first report that genes involved in VTE also predict CVD risk in NHL patients, particularly those treated with anthracycline chemotherapy. However, SNPs from genes previously associated with anthracycline-induced cardiotoxicity were not associated with CVD risk in this cohort, although those SNPs were identified in children and may not apply to adults. Future research will need to validate these findings and identify additional genetic markers that can be incorporated into risk assessment for CVD in this patient population. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Multi-trajectories of lipid indices with incident cardiovascular disease, heart failure, and all-cause mortality: 23 years follow-up of two US cohort studies

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fatemeh Koohi ◽  
Davood Khalili ◽  
Mohammad Ali Mansournia ◽  
Farzad Hadaegh ◽  
Hamid Soori
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cohort Studies ◽  
Significant Risk ◽  
Density Lipoprotein ◽  
Lipid Levels ◽  
Cvd Risk ◽  
All Cause Mortality ◽  
Over Time

Abstract Background Understanding the distinct patterns (trajectories) of variation in blood lipid levels before diagnosing cardiovascular disease (CVD) might carry important implications for improving disease prevention or treatment. Methods We investigated 14,373 participants (45.5% men) aged 45–84 from two large US prospective cohort studies with a median of 23 years follow-up. First, we jointly estimated developmental trajectories of lipid indices, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) concentrations using group-based multi-trajectory modeling. Then, the association of identified multi-trajectories with incident CVD, heart failure, and all-cause mortality were examined using Cox proportional hazard model. Results Seven distinct multi-trajectories were identified. The majority of participants (approximately 80%) exhibited decreasing LDL-C but rising TG levels and relatively stable HDL-C levels. Compared to the individuals with healthy and stable LDL-C, HDL-C, and TG levels, those in other groups were at significant risk of incident CVD after adjusting for other conventional risk factors. Individuals with the highest but decreasing LDL-C and borderline high and rising TG levels over time were at the highest risk than those in other groups with a 2.22-fold risk of CVD. Also, those with the highest and increased triglyceride levels over time, over optimal and decreasing LDL-C levels, and the lowest HDL-C profile had a nearly 1.84 times CVD risk. Even individuals in the multi-trajectory group with the highest HDL-C, optimal LDL-C, and optimal TG levels had a significant risk (HR, 1.45; 95% CI 1.02–2.08). Furthermore, only those with the highest HDL-C profile increased the risk of heart failure by 1.5-fold (95% CI 1.07–2.06). Conclusions The trajectories and risk of CVD identified in this study demonstrated that despite a decline in LDL-C over time, a significant amount of residual risk for CVD remains. These findings suggest the impact of the increasing trend of TG on CVD risk and emphasize the importance of assessing the lipid levels at each visit and undertaking potential interventions that lower triglyceride concentrations to reduce the residual risk of CVD, even among those with the optimal LDL-C level.

Cardiac Outcomes in a Prospective Cohort of Adult Non-Hodgkin Lymphoma Survivors

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2656-2656
Author(s):  
Carrie A. Thompson ◽  
Hongxiu Luo ◽  
Matthew J Maurer ◽  
Cristine Allmer ◽  
Thomas M. Habermann ◽  
...  
Keyword(s):  
Heart Disease ◽  
Hodgkin Lymphoma ◽  
Valvular Heart Disease ◽  
Mayo Clinic ◽  
Cumulative Incidence ◽  
Medical Records ◽  
P Value ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk

Abstract Abstract 2656 Background Treatment of non-Hodgkin lymphoma (NHL) can lead to development of cardiovascular disease (CVD). We sought to describe the cumulative incidence of CVD in adult NHL survivors diagnosed in the recent treatment era (since 2002) and identify clinical and treatment predictors for its development. Methods All patients were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). The MER offers enrollment to all consecutive patients with newly diagnosed NHL who are US residents and age >18 years. Clinical data from the time of diagnosis and treatment data are abstracted from medical records using a standard protocol. Patients are prospectively contacted via telephone or in person per protocol every 6 months for the first 3 years from diagnosis and yearly afterwards to assess disease status and development of comorbid conditions. CVD events, including heart failure (HF), myocardial infarction (MI), arrhythmia, pericarditis, and valvular heart disease, occurring after diagnosis were identified during follow-up and validated against medical records. HF was validated with the Cardiovascular Health Study Criteria and/or the Framingham Criteria. MI was validated using case definition standards of coronary heart disease, while arrhythmia, pericarditis, and valvular heart disease were validated using clinical definitions. The prevalence of CVD and associations between CVD and clinical characteristics (sex, age) and treatment (radiation, anthracyclines) were performed using Cox models with a competing risk approach. Results 1164 patients with NHL were enrolled into the MER at Mayo Clinic between 9/1/2002–2/28/2008. 646 were male (56%) and median age at diagnosis was 62 years (range 20–93). Median follow-up of all cases was 59 months (range 1–105). 131 patients reported CVD prior to the diagnosis of NHL and were excluded from analyses. An additional 76 patients did not have follow-up and were excluded. Of the 957 remaining patients, 75 (7.8%) self-reported a new diagnosis of CVD. Of these, 71 cases had available medical records. 57 of the 71 reviewed cases (80%) were validated (18 HF, 9 MI, 21 arrhythmia, 2 pericarditis, and 10 valvular heart disease). Cumulative incidence of CVD at 1, 3, 5, and 7 years was 1.3%, 3.7%, 5.2%, and 7.4%, respectively. Median time from NHL diagnosis to CVD was 26.5 months (range 1–84). Older age was associated with increased risk of overall CVD (p-value<0.001). Gender (p=0.59), radiation therapy (p=0.61), and anthracycline treatment (p=0.25) were not associated with the incidence of overall CVD. Among types of CVD, anthracycline use was associated with development of HF (HR=5.30; p-value=0.008) and arrhythmia (HR=2.68; p-value=0.04). Radiation was associated with development of arrhythmia (HR=2.73; p-value=0.03), while older age was associated with development of HF (HR=1.36 per 5 year increment; p-value=0.003) and arrhythmia (HR=1.25 per 5 year increment; p-value=0.02). Conclusions The risk of CVD in patients with NHL is approximately 1% per year after the initial diagnosis of lymphoma. The most commonly occurring CVDs in this cohort of NHL survivors were arrhythmia and HF. Treatment with anthracyclines and radiation are associated with increased risk of developing some types of CVD. 80% of self-reported CVD events in NHL survivors were validated using epidemiologic criteria. Future studies will include building models incorporating comorbid health conditions and lifestyle factors to determine risk of CVD as well as the impact of CVD on quality of life. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Genetic Risk Factors for Cardiovascular Disease in Adult Lymphoma Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5215-5215
Author(s):  
Sunnia T Chen ◽  
Nicholas J Boddicker ◽  
Matthew J. Maurer ◽  
Cristine Allmer ◽  
Dennis P. Robinson ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Heart Disease ◽  
Board Of Directors ◽  
Research Funding ◽  
Competing Risk ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
New Onset

Purpose The development of cardiovascular disease (CVD) is a relatively rare but a clinically important adverse event in the treatment of lymphoma, particularly in individuals receiving anthracyclines. There are few studies assessing the role of germline genetic susceptibility as a predictor of CVD in this setting. We evaluated the association of 24 single nucleotide polymorphisms (SNPs) from candidate genes involved in anthracycline-induced cardiotoxicity, CVD, and venous thromboembolism with new-onset CVD in a prospective cohort of lymphoma patients treated in the modern era. Methods All patients were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE. Enrollment from 2002-2015 was offered to patients with newly diagnosed lymphoma who were age ≥18 years. Clinical, pathology and treatment data were abstracted using a standard protocol, and participants provided a peripheral blood sample, from which DNA was extracted. All patients were prospectively contacted every 6 months for the first 3 years from diagnosis and then annually thereafter to assess disease status, re-treatment and development of new morbidities, including CVD. Reported CVD events included congestive heart failure (CHF), coronary heart disease (CHD), arrhythmia, valvular heart disease (VHD), and other CVD. These events were identified during follow-up and validated against medical records. Genotyping was conducted using a custom Illumina iSelect platform with rigorous quality controls. For each SNP, Cox regression was used to estimate Hazard Ratios (HRs) and 95% confidence intervals (CI) with time to first CVD, using death without CVD as a competing risk. HRs were also obtained for time to CHF, using death without CVD as a competing risk. We also modeled these events for all patients and for patients receiving frontline anthracyclines. Each SNP was modeled as having a log-additive (per minor allele) effect in the regression model. An ordinal test was used to assess the trend, with a nominal P<0.05 considered statistically significant. Results There were a total of 3,063 newly diagnosed lymphoma patients (excluding chronic lymphocytic leukemia) with no history of CVD at time of lymphoma diagnosis, of which 1280 had genotype data available for analysis. The median age at diagnosis was 59 years (range, 18-95) and 56% were male. The most common subtypes were follicular (26.3%), diffuse large B-cell (23.2%), Hodgkin (11.3%), marginal zone (11.2%), mantle cell (6.3%) and T-cell (5.4%) lymphoma. Anthracycline-based chemotherapy as initial therapy was used in 52% of individuals. At a median follow-up of 6.9 years (range, 0.1-17.1), 363 (30.7%) patients died, and 173 (13.5%) had new-onset CVD after lymphoma diagnosis. There were 234 incident CVD events in the 173 patients: 49 CHD, 50 CHF, 27 VHD, 103 arrhythmias, and 5 other CVD. Results are shown in the Table. When assessing all CVD, F5 (rs4524) (HR=1.28, 95% CI=1.03-1.58) and F11 (rs4253399) (HR=1.30, 95% CI=1.06-1.61) were associated with CVD at P<0.05; both associations attenuated slightly when restricted to anthracycline-treated patients (F5 HR=1.18, 95% CI=0.89-1.57; F11 HR=1.23, 95% CI=0.92-1.65). F11 was more strongly associated with CHF (HR=1.55, 95% CI=1.03-2.34) and CHF in anthracycline-treated patients (HR=1.64, 95% CI=0.98-2.76). NCF4 (rs1883112) was marginally associated with lower risk of CVD overall (HR=0.81, 95% CI=0.66-1.00), and this association strengthened when restricted to anthracycline-treated patients (HR=0.67, 95% CI=0.49-0.91) and showed similar trends in HRs for CHF (HR=0.77, 95% CI=0.51-1.16) and CHF in anthracycline-treated patients (HR=0.72, 95% CI=0.41-1.28), although neither estimate was statistically significant at P<0.05. Finally, while XDH (rs2236168) was not associated with all CVD (HR=1.00, 95% CI=0.81-1.23), it was associated with CHF (HR=0.66, 95% CI=0.47-0.93) overall, but attenuated in anthracycline-treated patients (HR=0.81, 95% CI=0.55-1.18). Conclusions In this exploratory study of candidate SNPs from the literature, we found limited evidence for a role of germline genetic variability in predicting risk of CVD or CHF in a cohort of lymphoma patients, especially after accounting for multiple testing. To fully address this hypothesis, future studies will need larger sample sizes and more comprehensive genetic assessment. Disclosures Maurer: Celgene: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding. Nowakowski:NanoString: Research Funding; Genentech, Inc.: Research Funding; MorphoSys: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Curis: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Celgene: Consultancy, Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees. Cerhan:Celgene: Research Funding; NanoString: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Cardiovascular Disease in Women with Breast Cancer – A Nationwide Registry Study

2020 ◽  
Author(s):  
Marie Jakobsen ◽  
Christophe Kolodziejczyk ◽  
Morten Sall Jensen ◽  
Peter Bo Poulsen ◽  
Humma Khan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Pulmonary Embolism ◽  
Heart Disease ◽  
Pulmonary Heart Disease ◽  
Increased Risk ◽  
Different Types ◽  
Cardiovascular Disease In Women

Abstract Background: There is increasing concern about cardiovascular disease (CVD) after breast cancer (BC). The aim of this study was to estimate the prevalence of different types of CVD in women diagnosed with BC compared to cancer-free controls as well as the incidence of CVD after BC diagnosis.Methods: We performed a cohort study based on data from national registries covering the entire Danish population. We followed 16,505 cancer-naïve BC patients diagnosed from 2003 to 2007 five years before and up to 10 years after BC diagnosis compared to 165,042 cancer-free controls. Results: We found that 15.6% of BC patients were registered with at least one CVD diagnosis in hospital records before BC diagnosis. Overall, BC patients and controls were similar with regards to CVD comorbidity before BC diagnosis. After BC diagnosis, the incidence of all CVD diagnoses combined was significantly higher in BC patients than controls up to approximately 6 years after the index date (BC diagnosis). The incidence of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism remained higher in BC patients than controls during the entire 10 year follow-up period. Furthermore, we found that the risk of heart failure and thrombophlebitis/thrombosis was higher after chemotherapy. Conclusions: Focus on CVD in BC patients is important to ensure optimum treatment with regards to BC as well as possible CVD. Strategies to minimise and manage the increased risk of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism in BC patients are especially important.

scholarly journals Maternal Cardiovascular Disease After Pre-Eclampsia and Gestational Hypertension: A Narrative Review

2021 ◽  
pp. 155982762110379
Author(s):  
Clare Oliver-Williams ◽  
Jasmine D. Johnson ◽  
Catherine J. Vladutiu
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Gestational Hypertension ◽  
Later Life ◽  
Previous Literature ◽  
Narrative Review ◽  
Cvd Risk ◽  
Middle Income

Previous literature has highlighted that women who have a pregnancy affected by gestational hypertension or preeclampsia are at higher risk of cardiovascular disease (CVD) in later life. However, CVD is a composite of multiple outcomes, including coronary heart disease, heart failure, and stroke, and the risk of both CVD and hypertensive disorders of pregnancy varies by the population studied. We conducted a narrative review of the risk of cardiovascular outcomes for women with prior gestational hypertension and pre-eclampsia. Previous literature is summarized by country and ethnicity, with a higher risk of CVD and coronary heart disease observed after gestational hypertension and a higher risk of CVD, coronary heart disease and heart failure observed after pre-eclampsia in most of the populations studied. Only one study was identified in a low- or middle-income country, and the majority of studies were conducted in white or mixed ethnicity populations. We discuss potential interventions to mitigate cardiovascular risk for these women in different settings and highlight the need for a greater understanding of the epidemiology of CVD risk after gestational hypertension and pre-eclampsia outside of high-income, white populations.

scholarly journals Association between Soy Food and Dietary Soy Isoflavone Intake and the Risk of Cardiovascular Disease in Women: A Prospective Cohort Study in Korea

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1407
Author(s):  
Jihyun Im ◽  
Kyong Park
Keyword(s):  
Cardiovascular Disease ◽  
Postmenopausal Women ◽  
Premenopausal Women ◽  
Soy Isoflavones ◽  
Korean Women ◽  
Cvd Risk ◽  
Soy Isoflavone ◽  
Soy Foods ◽  
Cardiovascular Disease In Women

The association between soy food and soy isoflavone intake and cardiovascular disease (CVD) risk is uncertain, especially in women. We aimed to investigate this association in Korean women. We analyzed data from the Korean Genome and Epidemiology Study, including 4713 Korean women aged 40–69 years with no CVD or cancer at baseline. Dietary information was obtained using a validated semi-quantitative food frequency questionnaire, and the incidence of CVD was assessed using biennial self-reported questionnaires on medical history. The mean follow-up time was 7.4 years, during which 82 premenopausal and 200 postmenopausal women reported CVD incidence. The highest tofu, total soy foods, and dietary soy isoflavone intake groups were significantly associated with a decreased CVD risk in premenopausal women (tofu: hazard ratio (HR) 0.39; 95% confidence interval (CI), 0.19–0.80; total soy food: HR 0.36; 95% CI, 0.18–0.70; dietary soy isoflavones: HR 0.44; 95% CI, 0.22–0.89), whereas no association was observed in postmenopausal women. Other soy foods showed no association with CVD incidence. Dietary soy isoflavones and total soy foods are associated with a decreased CVD risk in premenopausal women. Among soy foods, only tofu showed significant health benefits.

Abstract MP013: Strong Inverse Relation between Physical Activity and Incidence of Cardiovascular Disease in African Americans: the Atherosclerosis Risk in Communities Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Elizabeth J Bell
Keyword(s):  
Physical Activity ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
African Americans ◽  
Risk Reduction ◽  
Atherosclerosis Risk In Communities ◽  
Baseline Visit ◽  
Atherosclerosis Risk

Introduction: Although there is substantial evidence that physical activity reduces risk of cardiovascular disease (CVD), the few studies that included African Americans offer inconclusive evidence and did not study stroke and heart failure separately. Objective: We examined, in African Americans and Caucasians in the Atherosclerosis Risk in Communities study (ARIC), the association of physical activity with CVD incidence (n=1,039) and its major components - stroke (n=350), heart failure (n=633), and coronary heart disease (n=442) - over a follow-up period of 21 years. Methods: ARIC is a population-based biracial cohort study of 45– to 64-yr-old adults at the baseline visit in 1987–89. Physical activity was assessed using the modified Baecke physical activity questionnaire and categorized by the American Heart Association’s ideal CVD health guidelines: poor, intermediate, and ideal physical activity. An incident CVD event was defined as the first occurrence of 1) heart failure, 2) definite or probable stroke, or 3) coronary heart disease, defined as a definite or probable myocardial infarction or definite fatal coronary heart disease. Results: We included 3,707 African Americans and 10,018 Caucasians free of CVD at the baseline visit. After adjustment for age, sex, cigarette smoking, alcohol intake, hormone therapy use, education, and ‘Western’ and ‘Prudent’ dietary pattern scores, higher physical activity was inversely related to CVD, heart failure, and coronary heart disease incidence in African Americans and Caucasians (p-values for trend tests <.0001), and with stroke in African Americans. Hazard ratios (95% confidence intervals) for CVD for intermediate and ideal physical activity, respectively, compared to poor, were similar by race: 0.65 (0.56, 0.75) and 0.59 (0.49, 0.71) for African Americans, and 0.74 (0.66, 0.83) and 0.67 (0.59, 0.75) for Caucasians (p-value for interaction = 0.38). Physical activity was also associated similarly in African Americans and Caucasians for each of the individual CVD outcomes (coronary heart disease, heart failure, and stroke), with an approximate one-third reduction in risk for intermediate and ideal physical activity versus poor physical activity- this reduction was statistically significant. Conclusions: In conclusion, our findings reinforce public health recommendations that regular physical activity is important for CVD risk reduction, including reductions in stroke and heart failure. They provide strong new evidence that this risk reduction applies to African Americans as well as Caucasians and support the idea that some physical activity is better than none.

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

Circulation ◽  
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.

Abstract P323: Pulse Pressure and Incident Acute Coronary Heart Disease Events in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Stephen P Glasser ◽  
Daniel L Halberg ◽  
Charles Sands ◽  
Paul Muntner ◽  
Monika Safford
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Racial Differences ◽  
Pulse Pressure ◽  
Proportional Hazards ◽  
Linear Trend ◽  
Cox Proportional Hazards ◽  
Cvd Risk

Background: Increased attention has been given to pulse pressure (PP) as a potential independent risk factor of cardiovascular disease. We examined the relationship between PP and incident acute coronary heart disease (CHD). Methods: We used data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study of 30,239 black and white participants aged 45 years or older and enrolled between 2003 and 2007. Baseline data included a 45-minute interview and in-home visit during which blood pressure was assessed and recorded as the average of two measurements obtained after a 5 minute seated rest. PP (SBP-DBP) was classified into 4 groups (<45, 45-54, 54.1-64, >64.1 mmHg). Telephone follow-up occurred every six months for self or proxy-reported suspected events, triggering medical record retrieval and adjudication by experts. Cox-proportional hazards models examined the association of incident CHD with PP groups, adjusting for socio-demographic and clinical risk factors. Results: This analysis included 22,909 participants free of CHD at baseline, with mean age 64.7±9.4 years; 40.4%were black, 44.6% were male and they experienced a total of 515 incident CHD events over a mean 3.4 yrs of follow-up (maximum 6 years). In unadjusted analyses, compared with PP<45 mmHg, each higher PP group had incrementally higher hazard ratios (HR) for incident CHD (HR 1.28 {95% CI 1.02-1.60}, 2.05 {1.63-2.56}, 3.82 {3.08-4.74}, p<0.001 for linear trend). This relationship persisted after fully adjusting including SBP for the highest PP group (HR 0.96 {0.75-1.21}, 1.12 {0.86-1.46}, 1.51 {1.09-2.10}, p trend <0.0001). Conclusions: High PP was associated with incident CHD, even when accounting for SBP and numerous other CVD risk factors.

Physical activity less than the recommended amount may prevent the onset of major biological risk factors for cardiovascular disease: a cohort study of 198 919 adults

2018 ◽  
Vol 54 (4) ◽  
pp. 238-244 ◽  
Author(s):  
David Martinez-Gomez ◽  
Irene Esteban-Cornejo ◽  
Esther Lopez-Garcia ◽  
Esther García-Esquinas ◽  
Kabir P Sadarangani ◽  
...  
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Highly Active ◽  
Atherogenic Dyslipidaemia

ObjectivesWe examined the dose–response relationship between physical activity (PA) and incidence of cardiovascular disease (CVD) risk factors in adults in Taiwan.MethodsThis study included 1 98 919 participants, aged 18–97 years, free of CVD, cancer and diabetes at baseline (1997–2013), who were followed until 2016. At baseline, participants were classified into five PA levels: inactive’ (0 metabolic equivalent of task (MET)-h/week), ‘lower insufficiently active’ (0.1–3.75 MET-h/week), ‘upper insufficiently active’ (3.75–7.49 MET-h/week), ‘active’ (7.5–14.99 MET-h/week) and ‘highly active’ (≥15 MET-h/week]. CVD risk factors were assessed at baseline and at follow-up by physical examination and laboratory tests. Analyses were performed with Cox regression and adjusted for the main confounders.ResultsDuring a mean follow-up of 6.0±4.5 years (range 0.5–19 years), 20 447 individuals developed obesity, 19 619 hypertension, 21 592 hypercholesterolaemia, 14 164 atherogenic dyslipidaemia, 24 275 metabolic syndrome and 8548 type 2 diabetes. Compared with inactive participants, those in the upper insufficiently active (but not active) category had a lower risk of obesity (HR 0.92; 95% CI 0.88 to 0.95), atherogenic dyslipidaemia (0.96; 0.90 to 0.99), metabolic syndrome (0.95; 0.92 to 0.99) and type 2 diabetes (0.91; 0.86 to 0.97). Only highly active individuals showed a lower incidence of CVD risk factors than their upper insufficiently active counterparts.ConclusionCompared with being inactive, doing half the recommended amount of PA is associated with a lower incidence of several common biological CVD risk factors. Given these benefits, half the recommended amount of PA is an evidence based target for inactive adults.

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