scholarly journals Does weight mediate the effect of smoking on coronary heart disease? Parametric mediational g-formula analysis

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262403
Author(s):  
Yaser Mokhayeri ◽  
Maryam Nazemipour ◽  
Mohammad Ali Mansournia ◽  
Ashley I. Naimi ◽  
Jay S. Kaufman

Background In settings in which there are time-varying confounders affected by previous exposure and a time-varying mediator, natural direct and indirect effects cannot generally be estimated unbiasedly. In the present study, we estimate interventional direct effect and interventional indirect effect of cigarette smoking as a time-varying exposure on coronary heart disease while considering body weight as a time-varying mediator. Methods To address this problem, the parametric mediational g-formula was proposed to estimate interventional direct effect and interventional indirect effect. We used data from the Multi-Ethnic Study of Atherosclerosis to estimate effect of cigarette smoking on coronary heart disease, considering body weight as time-varying mediator. Results Over a 11-years period, smoking 20 cigarettes per day compared to no smoking directly (not through weight) increased risk of coronary heart disease by an absolute difference of 1.91% (95% CI: 0.49%, 4.14%), and indirectly decreased coronary heart disease risk by -0.02% (95% CI: -0.05%, 0.04%) via change in weight. The total effect was estimated as an absolute 1.89% increase (95% CI: 0.49%, 4.13%). Conclusion The overall absolute impact of smoking to incident coronary heart disease is modest, and we did not discern any important contribution to this effect relayed through changes to bodyweight. In fact, changes in weight because of smoking have no meaningful mediating effect on CHD risk.

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Elizabeth J Bell ◽  
Jennifer L St. Sauver ◽  
Veronique L Roger ◽  
Nicholas B Larson ◽  
Hongfang Liu ◽  
...  

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.


2018 ◽  
Vol 25 (6) ◽  
pp. 598-605 ◽  
Author(s):  
G David Batty ◽  
Keum Ji Jung ◽  
Yejin Mok ◽  
Sun Ju Lee ◽  
Joung Hwan Back ◽  
...  

Aims Systematic reviews report an association between poorer oral health and an increased risk of coronary heart disease. This contentious relationship may not be causal but existing studies have been insufficiently well powered comprehensively to examine the role of confounding, particularly by cigarette smoking. Accordingly, we sought to examine the role of smoking in generating the relationship between oral health and coronary heart disease in life-long non-smokers. Methods and results In the Korean Cancer Prevention Study, 975,685 individuals (349,579 women) aged 30–95 years had an oral examination when tooth loss, a widely used indicator of oral health, was ascertained. Linkage to national mortality and hospital registers over 21 years of follow-up gave rise to 64,784 coronary heart disease events (19,502 in women). In the whole cohort, after statistical adjustment for age, there was a moderate, positive association between tooth loss and coronary heart disease in both men (hazard ratio for seven or more missing teeth vs. none; 95% confidence interval 1.08; 1.02, 1.14; Ptrend across tooth loss groups <0.0001) and women (1.09; 1.01, 1.18; Ptrend 0.0016). Restricting analyses to a subgroup of 464,145 never smokers (25,765 coronary heart disease events), however, resulted in an elimination of this association in men (1.01; 0.85, 1.19); Ptrend 0.7506) but not women (1.08; 0.99, 1.18; Ptrend 0.0086). Conclusion In men in the present study, the relationship between poor oral health and coronary heart disease risk appeared to be explained by confounding by cigarette smoking so raising questions about a causal link.


2021 ◽  
pp. jech-2020-214358
Author(s):  
Pekka Martikainen ◽  
Kaarina Korhonen ◽  
Aline Jelenkovic ◽  
Hannu Lahtinen ◽  
Aki Havulinna ◽  
...  

BackgroundGenetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.MethodsThe data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.ResultsAllowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.ConclusionsPRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.


2017 ◽  
Vol 3 ◽  
pp. 233372141769667 ◽  
Author(s):  
Minjee Lee ◽  
M. Mahmud Khan ◽  
Brad Wright

Objective: We investigated the association between childhood socioeconomic status (SES) and coronary heart disease (CHD) in older Americans. Method: We used Health and Retirement Study data from 1992 to 2012 to examine a nationally representative sample of Americans aged ≥50 years ( N = 30,623). We modeled CHD as a function of childhood and adult SES using maternal and paternal educational level as a proxy for childhood SES. Results: Respondents reporting low childhood SES were significantly more likely to have CHD than respondents reporting high childhood SES. Respondents reporting both low childhood and adult SES were 2.34 times more likely to have CHD than respondents reporting both high childhood and adult SES. People with low childhood SES and high adult SES were 1.60 times more likely than people with high childhood SES and high adult SES to report CHD in the fully adjusted model. High childhood SES and low adult SES increased the likelihood of CHD by 13%, compared with high SES both as a child and adult. Conclusion: Childhood SES is significantly associated with increased risk of CHD in later life among older adult Americans.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Elena M. Yubero-Serrano ◽  
Juan F. Alcalá-Diaz ◽  
Francisco M. Gutierrez-Mariscal ◽  
Antonio P. Arenas-de Larriva ◽  
Patricia J. Peña-Orihuela ◽  
...  

Abstract Background Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association. Methods CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma was performed. Results The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment. Conclusions Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients. Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT00924937. Unique Identifier: NCT00924937


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Monica C Klempel ◽  
Cynthia M Kroeger ◽  
Krista A Varady

Background: Alternate day fasting (ADF) with a low-fat (LF) diet is effective for weight loss and cardio-protection. However, the applicability of these findings is questionable as most Americans consume a high-fat (HF) diet. This study examined if these beneficial changes in weight and coronary heart disease (CHD) risk can be reproduced if a HF diet is used in place of a LF diet during ADF. Methods: Thirty-two obese subjects were randomized to an ADF-HF (45% fat) or ADF-LF diet (25% fat), which consisted of two phases: 1) a 2-week baseline weight maintenance period, and 2) an 8-week ADF weight loss period. All food was provided to subjects. Results: Body weight was reduced (P < 0.0001) by ADF-HF (5 ± 1%) and by ADF-LF (4 ± 1%). Fat mass decreased (P < 0.0001) by ADF-HF (5 ± 1 kg) and ADF-LF (4 ± 1 kg). Fat free mass remained unchanged. Waist circumference decreased (P < 0.001) by ADF-HF (7 ± 1 cm) and ADF-LF (7 ± 1 cm). LDL cholesterol and triacylglycerol concentrations were reduced (P < 0.01) by both interventions (ADF-HF: 18 ± 5%, 14 ± 5%; ADF-LF: 24 ± 3%, 14 ± 4%). The proportion of small LDL particles decreased (P < 0.05) in the ADF-HF and ADF-LF groups by 8 ± 3% and 10 ± 4%. Conclusion: Thus, an ADF-HF diet produces similar reductions in weight and CHD risk as an ADF-LF diet. These findings are important in terms of diet tolerability and long-term adherence to ADF diets.


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