Phthalate Exposure and Coronary Heart Disease: Possible Implications of Oxidative Stress and Altered miRNA Expression.

The relationship between phthalate exposure and coronary heart disease (CHD) is still unclear. This study aimed to investigate the association between phthalate exposure and CHD and determine the possible atherogenic mechanisms of phthalates by assessing oxidative stress and altering miRNA expression. This case-control study included 110 participants (55 CHD patients and 55 healthy controls). The levels of oxidative stress markers, malondialdehyde (MDA), and superoxide dismutase (SOD), and the expression of miRNA-155 (miR-155) and miRNA-208a (miR-208a), were measured and correlated with the urinary mono-2-ethylhexyl phthalate (MEHP). Highly significant differences were detected between the CHD cases and the control group regarding MEHP, MDA, SOD, miR-155, and miR-208a (p-value < 0.001). Spearman correlations revealed a significant positive correlation between MDA and MEHP in urine (P = 0.001 and rs = 0.316) and a significant negative correlation between SOD and MEHP in urine (P < 0.001 and rs = -0.345). Furthermore, significant positive correlations were observed between miR-155 and urinary MEHP (P = 0.001 and rs = 0.318) and miR-208a and urinary MEHP (P < 0.001 and rs = -0.352). This study revealed an association between phthalate exposure, as indicated by urinary MEHP and CHD; altered expression of miR-155 and miR-208a and oxidative stress could be the fundamental mechanisms.

Is residential exposure to oil refineries a novel contextual risk factor for coronary heart disease?

Despite a multi-decade decrease in cardiovascular disease, geographic disparities have widened, with excess mortality concentrated within the United States (U.S.) South. Petroleum production and refining, a major contributor to climate change, is concentrated within the U.S. South and emits multiple classes of atherogenic pollutants. We investigated whether residential exposure to oil refineries could explain variation in self-reported coronary heart disease (CHD) prevalence among adults in southern states for the year 2018, where the majority of oil refinery activity occurs (Alabama, Mississippi, Louisiana, Arkansas, Texas, New Mexico, and Oklahoma). We examined census tract-level association between oil refineries and CHD prevalence. We used a double matching method to adjust for measured and unmeasured spatial confounders: one-to-n distance matching and one-to-one generalized propensity score matching. Exposure metrics were constructed based on proximity to refineries, activities of refineries, and wind speed/direction. For all census tracts within 10 km of refineries, self-reported CHD prevalence ranged from 1.2% to 17.6%. Compared to census tracts located at ≥5 km and <10 km, one standard deviation increase in the exposure within 5 km of refineries was associated with a 0.33 (95% confidence interval: 0.04, 0.63) percentage point increase in the prevalence. A total of 1119.0 (123.5, 2114.2) prevalent cases or 1.6% (0.2, 3.1) of CHD prevalence in areas within 5 km from refineries were potentially explained by exposure to oil refineries. At the census tract-level, the prevalence of CHD explained by exposure to oil refineries ranged from 0.02% (0.00, 0.05) to 47.4% (5.2, 89.5). Thus, although we cannot rule out potential confounding by other personal risk factors, CHD prevalence was found to be higher in populations living nearer to oil refineries, which may suggest that exposure to oil refineries can increase CHD risk, warranting further investigation.

Correlation of heavy metals' exposure with the prevalence of coronary heart disease among US adults: findings of the US NHANES from 2003 to 2018.

We sought to explore the association between heavy metal exposure and coronary heart disease (CHD) based on data from the US National Health and Nutrition Examination Survey (NHANES, 2003-2018). In the analyses, participants were all aged > 20 and had participated in heavy metal sub-tests with valid CHD status. The Mann-Kendall test was employed to assess the trends in heavy metals' exposure and the trends in CHD prevalence over 16 years. Spearman's rank correlation coefficient and a logistics regression (LR) model were used to estimate the association between heavy metals and CHD prevalence. 42,749 participants were included in our analyses, 1802 of whom had a CHD diagnosis. Total arsenic, dimethylarsonic acid, monomethylarsonic acid, barium, cadmium, lead, and antimony in urine, and cadmium, lead, and total mercury in blood all showed a substantial decreasing exposure level tendency over the 16 years (all Pfor trend < 0.05). CHD prevalence varied from 3.53 to 5.23% between 2003 and 2018. The correlation between 15 heavy metals and CHD ranges from - 0.238 to 0.910. There was also a significant positive correlation between total arsenic, monomethylarsonic acid, and thallium in urine and CHD by data release cycles (all P < 0.05). The cesium in urine showed a negative correlation with CHD (P < 0.05). We found that exposure trends of total arsenic, dimethylarsonic acid, monomethylarsonic acid, barium, cadmium, lead, and antimony in urine and blood decreased. CHD prevalence fluctuated, however. Moreover, total arsenic, monomethylarsonic acid, and thallium in urine all showed positive relationships with CHD, while cesium in urine showed a negative relationship with CHD.

Plasma concentration of atorvastatin metabolites correlates with low-density lipoprotein cholesterol reduction in patients with coronary heart disease.

In this exploratory study from a randomized double-blinded crossover trial including 70 patients with coronary heart disease and self-perceived muscular side effects of statins, we aimed to determine the relationship between low-density lipoprotein cholesterol (LDL-C) reduction and atorvastatin metabolite plasma concentrations. All patients underwent a 7 weeks treatment period with atorvastatin 40 mg/day and a 7 weeks placebo period in random order. Nonlinear regression with a three-parameter equation explored the relationship between percentage LDL-C reduction (statin vs. placebo) and the pharmacokinetic variables. Mean LDL-C reduction was 49% (range 12% to 71%). The sum of 4-OH-atorvastatin acid and lactone correlated moderately with the LDL-C response (Spearman ρ 0.27, 95% confidence interval [CI]: 0.03 to 0.48). Accordingly, nonlinear regression showed R2 of 0.14 (95% CI: 0.03 to 0.37, R2 adjusted equaled 0.11). Even a perfect underlying correlation of 1.0 showed R2 = 0.32 by simulation, using historical intra-individual LDL-C variation (8.5%). The 90% inhibitory concentration was 2.1 nmol/L, and the 4-OH-metabolite sum exceeded this threshold in 34% of the patients. In conclusion, trough plasma concentrations of 4-OH-atorvastatin metabolites correlated moderately to the LDL-C reduction. A plateau LDL-C response was observed above a pharmacokinetic threshold, below which the response was highly variable. The usefulness of monitoring concentrations of atorvastatin metabolites to optimize the individual dosage have limitations, but its supportive potential may be pursued in relevant patient subsets to achieve adequate efficacy at the lowest possible dose. The results add knowledge to the overall understanding of the variable LDL-C response mediated by atorvastatin.

Volatile Hydrocarbon Exposures and Incident Coronary Heart Disease Events: Up to Ten Years of Follow-up among Deepwater Horizon Oil Spill Workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, response and cleanup workers were potentially exposed to toxic volatile components of crude oil. However, to our knowledge, no study has examined exposure to individual oil spill-related chemicals in relation to cardiovascular outcomes among oil spill workers. OBJECTIVES: Our aim was to investigate the association of several spill-related chemicals [benzene, toluene, ethylbenzene, xylene, n-hexane (BTEX-H)] and total hydrocarbons (THC) with incident coronary heart disease (CHD) events among workers enrolled in a prospective cohort. METHODS: Cumulative exposures to THC and BTEX-H across the cleanup period were estimated via a job-exposure matrix that linked air measurement data with self-reported DWH spill work histories. We ascertained CHD events following each worker's last day of cleanup work as the first self-reported physician-diagnosed myocardial infarction (MI) or a fatal CHD event. We estimated hazard ratios (HR) and 95% confidence intervals for the associations of exposure quintiles (Q) with risk of CHD. We applied inverse probability weights to account for bias due to confounding and loss to follow-up. We used quantile g-computation to assess the joint effect of the BTEX-H mixture. RESULTS: Among 22,655 workers with no previous MI diagnoses, 509 experienced an incident CHD event through December 2019. Workers in higher quintiles of each exposure agent had increased CHD risks in comparison with the referent group (Q1) of that agent, with the strongest associations observed in Q5 (range of HR=1.14-1.44). However, most associations were nonsignificant, and there was no evidence of exposure-response trends. We observed stronger associations among ever smokers, workers with ≤high school education, and workers with body mass index <30 kg/m2. No apparent positive association was observed for the BTEX-H mixture. CONCLUSIONS: Higher exposures to volatile components of crude oil were associated with modest increases in risk of CHD among oil spill workers, although we did not observe exposure-response trends. https://doi.org/10.1289/EHP11859.

Co-Exposure to Bisphenols, Parabens, and Antimicrobials and Association with Coronary Heart Disease: Oxidative Stress as a Potential Mediating Factor?

Coronary heart disease (CHD) is the leading cause of global morbidity, but the effect of plasticizers and antimicrobial additives on CHD is unknown. Here, we conducted a case-control study to investigate the mediating role of oxidative stress in the association between co-exposure to seven bisphenols, four parabens, triclosan (TCS), triclocarban, and CHD risk in Guangzhou, China. Quantile-based g-computation and weighted quantile sum regression were used to analyze mixture-outcome associations. Quantile-based g-computation showed a positive joint effect of a decile increase in exposure to all examined pollutants on CHD risk (OR: 1.52, 95% CI: 1.25-1.84), with bisphenol A (BPA), bisphenol F (BPF), n-butyl paraben (BuP), and TCS representing major contributors. The results also showed a decile nonmonotonic increase in the exposure mixtures, positively correlated with a 2.22 ng/mL (95% CI: 1.21-3.23 ng/mL) elevation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), with BuP, TCS, bisphenol AP (BPAP), and BPF contributing dominantly. Mediation analysis showed that 8-OHdG mediated the relationship between BPA, BPF, BPAP, and TCS, and CHD risk. Moreover, the mediating role of high-density lipoprotein (HDL) between several bisphenols and CHD was also identified. It is yet to be verified, but bisphenols may elevate CHD risk by reducing HDL status and increasing oxidative stress.

Fine particulate matter and incident coronary heart disease events up to 10 years of follow-up among Deepwater Horizon oil spill workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, in-situ burning and flaring were conducted to remove oil from the water. Workers near combustion sites were potentially exposed to burning-related fine particulate matter (PM2.5). Exposure to PM2.5 has been linked to increased risk of coronary heart disease (CHD), but no study has examined the relationship among oil spill workers. OBJECTIVES: To investigate the association between estimated PM2.5 from burning/flaring of oil/gas and CHD risk among the DWH oil spill workers. METHODS: We included workers who participated in response and cleanup activities on the water during the DWH disaster (N = 9091). PM2.5 exposures were estimated using a job-exposure matrix that linked modelled PM2.5 concentrations to detailed DWH spill work histories provided by participants. We ascertained CHD events as the first self-reported physician-diagnosed CHD or a fatal CHD event that occurred after each worker's last day of burning exposure. We estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for the associations between categories of average or cumulative daily maximum PM2.5 exposure (versus a referent category of water workers not near controlled burning) and subsequent CHD. We assessed exposure-response trends by examining continuous exposure parameters in models. RESULTS: We observed increased CHD hazard among workers with higher levels of average daily maximum exposure (low vs. referent: HR = 1.26, 95% CI: 0.93, 1.70; high vs. referent: HR = 2.11, 95% CI: 1.08, 4.12; per 10 µg/m3 increase: HR = 1.10, 95% CI: 1.02, 1.19). We also observed suggestively elevated HRs among workers with higher cumulative daily maximum exposure (low vs. referent: HR = 1.19, 95% CI: 0.68, 2.08; medium vs. referent: HR = 1.38, 95% CI: 0.88, 2.16; high vs. referent: HR = 1.44, 95% CI: 0.96, 2.14; per 100 µg/m3-d increase: HR = 1.03, 95% CI: 1.00, 1.05). CONCLUSIONS: Among oil spill workers, exposure to PM2.5 from flaring/burning of oil/gas was associated with increased risk of CHD.

Effectiveness of Simvastatin Versus Gemfibrozil for Primary Prevention of Cardiovascular Events: A Retrospective Cohort Study of 223,699 Primary Care Patients.

BACKGROUND AND OBJECTIVE: Evidence of the effectiveness of statins compared with fibrates for primary prevention of cardiovascular events is limited. Therefore, we assessed the comparative effectiveness of simvastatin versus gemfibrozil for primary prevention of major adverse cardiovascular events (MACE) and mortality. METHODS: This territory-wide cohort study used electronic health records of simvastatin and gemfibrozil prescriptions from the Hong Kong Hospital Authority and compared simvastatin or gemfibrozil initiation. The primary outcome was MACE, defined as the composite of the first diagnosis of cardiovascular mortality, coronary heart disease, or stroke. Secondary outcomes were the individual components of MACE, all-cause mortality, and non-cardiovascular mortality. Inverse probability of treatment weighting on the propensity score was used to estimate hazard ratios (HRs). RESULTS: A total of 223,699 individuals (120,207 [53.7%] women; median follow-up 7.0 years [interquartile range 5.7-9.1]) who were prescribed simvastatin (n = 168,630) or gemfibrozil (n = 55,069) were included. Simvastatin was associated with a reduced risk of MACE (HR 0.90, 95% confidence interval [CI] 0.88-0.93), all-cause mortality (HR 0.88, 95% CI 0.86-0.90), cardiovascular mortality (HR 0.71, 95% CI 0.67-0.76), and non-cardiovascular mortality (HR 0.92, 95% CI 0.89-0.95). Associations for MACE varied according to baseline characteristics with gemfibrozil being associated with a reduced risk of MACE in men and patients with low baseline high-density lipoprotein (HDL) cholesterol (< 1.0 mmol/L). CONCLUSION: The results of this study showed better population-level effectiveness of simvastatin compared with gemfibrozil for the primary prevention of MACE; however, a definitive randomized controlled trial is required to compare simvastatin with gemfibrozil among patients with low HDL cholesterol, as they appear to obtain benefit with gemfibrozil.

Effects of tiotropium on the risk of coronary heart disease in patients with COPD: a nationwide cohort study.

Inhaled long-acting muscarinic antagonist (LAMA) is recommended for the treatment of chronic obstructive pulmonary disease (COPD). However, there is still concern that LAMA may cause cardiovascular adverse events in COPD patients. Therefore, this study aimed to determine whether the administration of tiotropium, the first commercially available LAMA, could increase the risk of coronary heart disease (CHD) in COPD patients through a nationwide cohort study. We used the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) database between 2002 and 2014 for the analysis. We applied a washout period of COPD diagnosis during 2002-2003 and excluded the patients who used an inhaler before the diagnosis of COPD. We also excluded patients who were diagnosed with CHD before inhaler use. Among a total of 5787 COPD patients, 1074 patients were diagnosed with CHD. In the Cox regression models with time-dependent tiotropium usage, we found that tiotropium significantly increased the risk of CHD in a subgroup of age [Formula: see text]55 years compared to non-users of tiotropium (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [CI], 1.003-1.54). When analyzed by dividing into tertiles (high/middle/low) according to the cumulative tiotropium exposure, the high tertile exposure group of tiotropium was associated with a higher risk of CHD compared with the low tertile exposure group of tiotropium. Additionally, the risk of CHD was higher in the high tertile exposure group of tiotropium in the age 55 and older group and in the never smoker group. When prescribing tiotropium for COPD patients, particularly those over 55 years of age and never-smokers, it is desirable to evaluate the risk of CHD in advance and closely follow-up for CHD occurrence.

Added Sugar, Sugar-Sweetened Beverages, and Artificially Sweetened Beverages and Risk of Cardiovascular Disease: Findings from the Women's Health Initiative and a Network Meta-Analysis of Prospective Studies.

Much remains unknown about the role of added sugar in relation to cardiovascular disease (CVD) and the relative contributions of sugar-sweetened beverages (SSB) or artificially sweetened beverages (ASB) to CVD risk. Among the 109,034 women who participated in Women's Health Initiative, we assessed average intakes of added sugar, SSB and ASB, and conducted Cox regression to estimate the hazard ratios (HRs) and their 95% confidence intervals for CVD risk. The consistency of findings was compared to a network meta-analysis of all available cohorts. During an average of 17.4 years of follow-up, 11,597 cases of total CVD (nonfatal myocardial infarction, coronary heart disease (CHD) death, stroke, coronary revascularization, and/or incident heart failure) were confirmed. Added sugar as % energy intake daily (%EAS) at ≥15.0% was positively associated with total CVD (HR = 1.08 [1.01, 1.15]) and CHD (HR = 1.20 [1.09, 1.32]). There was also a higher risk of total CVD associated with ≥1 serving of SSB intake per day (HR = 1.29 [1.17, 1.42]), CHD (1.35 [1.16, 1.57]), and total stroke (1.30 [1.10, 1.53]). Similarly, ASB intake was associated with an increased risk of CVD (1.14 [1.03, 1.26]) and stroke (1.24 [1.04, 1.48]). According to the network meta-analysis, there was a large amount of heterogeneity across studies, showing no consistent pattern implicating added sugar, ASB, or SSB in CVD outcomes. A diet containing %EAS ≥15.0% and consuming ≥1 serving of SSB or ASB may be associated with a higher CVD incidence. The relative contribution of added sugar, SSB, and ASB to CVD risk warrants further investigation.

Evaluation of ABC Bleeding Score and SAMe-TT2R2 Score on the Risk of Bleeding after Anticoagulation in Patients with Nonvalvular Atrial Fibrillation Complicated with Coronary Heart Disease.

Objective: To explore the predictive value of ABC bleeding score and SAMe-TT2R2 score on the risk of bleeding in patients with nonvalvular atrial fibrillation (NVAF) complicated with coronary heart disease (CHD) after anticoagulation. Methods: 149 patients with NVAF complicated with CHD were followed up in our hospital for one year. The bleeding events during the follow-up period were observed, the ABC bleeding score and SAMe-TT2R2 score were calculated, the predictive value of the two scoring methods for the main bleeding risk was analyzed by the ROC curve, and the AUC area under the ROC curve of the two scoring methods was compared by the Delong test. Results: There were 32 bleeding events during the follow-up period. The AUC of ABC bleeding score and SAMe-TT2R2 score were 0.775 (P < 0.01) and 0.624 (P < 0.05), respectively. The Delong test showed that the AUC of ABC bleeding score was significantly higher than that of SAMe-TT2R2 score (d = 2.177, P < 0.05). Conclusion: Both the ABC bleeding score and SAMe-TT2R2 score can predict the risk of bleeding after anticoagulation in patients with NVAF and CHD. The critical value of the SAMe-TT2R2 score for predicting bleeding events in patients with NVAF and CHD may need to be increased to 4 or 5, and the prediction ability of ABC bleeding score is significantly better than that of the SAMe-TT2R2 score.

A nationwide cohort study suggests clarithromycin-based therapy for Helicobacter pylori eradication is safe in patients with stable coronary heart disease and subsequent peptic ulcer disease.

BACKGROUND: Clarithromycin-based therapy is important for Helicobacter pylori eradication treatment. However, clarithromycin may increase cardiovascular risk. Hence, we investigated the association between clarithromycin use and outcomes in adults with stable coronary heart disease (CHD) and subsequent peptic ulcer disease (PUD). METHODS: This nationwide cohort study used a national health insurance database to screen 298,417 Taiwanese residents who were diagnosed with coronary heart disease from 2001 to 2015 for eligibility in the study and to evaluate select eligible patients with CHD-PUD from 2004 to 2015. Data were obtained from new users of clarithromycin (n = 4183) and nonusers of clarithromycin (n = 24,752) during follow-up. A total of 4070 eligible clarithromycin users and 4070 nonusers were subject to final analysis by 1:1 propensity score matching. Participants were followed up after receiving clarithromycin or at the corresponding date until the occurrence of cardiovascular morbidity in the presence of competing mortality, overall mortality and cardiovascular mortality, or through the end of 2015. The incidence rates and risks of overall mortality and cardiovascular outcomes were evaluated. The associations between clarithromycin and arrhythmia risk, as well as its dose and duration and overall mortality and cardiovascular outcomes were also addressed. RESULTS: Clarithromycin users were associated with adjusted hazard ratios of 1.08 (95% confidence interval, 0.93-1.24; 21.5 compared with 21.2 per 1000 patient-years) for overall mortality, 0.95 (0.57-1.59; 1.5 compared with 1.8 per 1000 patient-years) for cardiovascular mortality, and 0.94 (0.89-1.09; 19.6 compared with 20.2 per 1000 patient-years) for cardiovascular morbidity in the presence of competing mortality, as compared with nonusers. We found no relationship between dose and duration of clarithromycin and overall mortality and cardiovascular outcomes and no increased risk of arrhythmia during follow-up period. After inclusion of arrhythmia events to re-estimate the risks of all study outcomes, the results remained insignificant. CONCLUSION: Concerning overall mortality, cardiovascular mortality, and cardiovascular morbidity, our results suggest clarithromycin-based therapy for Helicobacter pylori eradication may be safe in patients with stable CHD and subsequent PUD.

Association between fine particulate matter and coronary heart disease: A miRNA microarray analysis.

Several studies have reported an association between residential surrounding particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) and coronary heart disease (CHD). However, the underlying biological mechanism remains unclear. To fill this research gap, this study enrolled a residentially stable sample of 942 patients with CHD and 1723 controls. PM2.5 concentration was obtained from satellite-based annual global PM2.5 estimates for the period 1998-2019. MicroRNA microarray and pathway analysis of target genes was performed to elucidate the potential biological mechanism by which PM2.5 increases CHD risk. The results showed that individuals exposed to high PM2.5 concentrations had higher risks of CHD than those exposed to low PM2.5 concentrations (odds ratio = 1.22, 95% confidence interval: 1.00, 1.47 per 10 µg/m3 increase in PM2.5). Systolic blood pressure mediated 6.6% of the association between PM2.5 and CHD. PM2.5 and miR-4726-5p had an interaction effect on CHD development. Bioinformatic analysis demonstrated that miR-4726-5p may affect the occurrence of CHD by regulating the function of RhoA. Therefore, individuals in areas with high PM2.5 exposure and relative miR-4726-5p expression have a higher risk of CHD than their counterparts because of the interaction effect of PM2.5 and miR-4726-5p on blood pressure.

Monitoring Simvastatin Adherence in Patients With Coronary Heart Disease: A Proof-of-Concept Study Based on Pharmacokinetic Measurements in Blood Plasma.

BACKGROUND: Poor statin adherence remains a public health concern associated with adverse outcomes. We evaluated the use of pharmacokinetic measurements to monitor adherence to simvastatin in patients with coronary heart disease (CHD). METHODS: Eighteen patients with CHD taking an evening dose of simvastatin 20 mg (n = 7), 40 mg (n = 5), or 80 mg (n = 6) were examined at steady-state pharmacokinetics. Ten patients were instructed to interrupt simvastatin dosing and return for blood sampling for the subsequent 3 days. Dose-normalized plasma concentrations of simvastatin lactone and simvastatin acid and the sum of the 2 were evaluated to discriminate between adherent dosing and dose omission. Bioanalytical quantification was performed using liquid chromatography-tandem mass spectrometry. RESULTS: A simvastatin acid cutoff of 1.0 × 10 -2 nmol -1 ·L -1 ·mg -1 identified 100% of those omitting 2 doses and 60% of those omitting a single dose. Simvastatin acid showed superior ability to discriminate dose omission, as well as the best agreement between samples handled at ambient and cool temperatures (median deviation 3.5%; interquartile range -2.5% to 13%). The cutoff for a morning dose schedule, with a similar ability to discriminate, was estimated at 2.0 × 10 -3 nmol -1 ·L -1 ·mg -1 . CONCLUSIONS: The present method discriminated between adherence and reduced adherence to simvastatin therapy in patients with CHD. Sample handling is feasible for routine practice, and the assessment of adherence can be performed by direct measurement of simvastatin acid in a blood sample, according to defined cutoff values. Further studies validating the cutoff value and utility for clinical application are encouraged.

The burden of coronary heart disease and stroke attributable to dietary cadmium exposure in Chinese adults, 2017.

Cadmium (Cd) is a metal with a long biological half-life that could cause health issues, such as coronary heart disease (CHD), stroke, and other cardiovascular diseases (CVD). Recent studies showed an ascending trend in the dietary Cd intake in the Chinese population. The contribution of dietary Cd intake to CHD and stroke burden, on the other hand, remains to be established. To calculate the disease burden for CHD and stroke attributable to dietary Cd, we estimated dietary Cd intake by associating the Cd concentration in food with consumption frequency. The toxicokinetic (TK) model and dietary Cd consumption were used to simulate urinary cadmium (U-Cd) concentrations. The population attributable fraction (PAF) can be derived for the computation of the attributable disease burden expressed as Disability-Adjusted Life Years (DALYs) in provinces, genders, and age groups by combining the relative risk (RR) with the population distribution of U-Cd. The mean of dietary Cd consumption and the geometric mean of U-Cd in the Chinese adult population are 0.684 µg/kg bw/day and 0.88 µg/g creatinine. The CHD burden attributable to dietary Cd was 3.26 million DALYs, with a 9.69% proportion of the total CHD burden. The DALYs for stroke attributable to Cd in food was approximately 3.64 million, accounting for 8.22% of the overall stroke burden. Furthermore, the attributable disease burden of CHD and stroke are higher in the south, women, and middle-aged and older adults. Our study suggested that foodborne Cd exposure contributes a considerable proportion of the CHD and stroke burden. More attention is needed to control Cd in food in order to reduce the burden of CHD and stroke in the Chinese population.

The short-term effects and burden of particle air pollution on hospitalization for coronary heart disease: a time-stratified case-crossover study in Sichuan, China.

BACKGROUND: Coronary heart disease (CHD), the leading cause of death globally, might be developed or exacerbated by air pollution, resulting high burden to patients. To date, limited studies have estimated the relations between short-term exposure to air pollution and CHD disease burden in China, with inconsistent results. Hence, we aimed to estimate the short-term impact and burden of ambient PM pollutants on hospitalizations of CHD and specific CHD. METHODS: PM10 and PM2.5 were measured at 82 monitoring stations in 9 cities in Sichuan Province, China during 2017-2018. Based on the time-stratified case-crossover design, the effects of short-term exposure to particle matter (PM) pollution on coronary heart disease (CHD) hospital admissions were estimated. Meanwhile, the linked burden of CHD owing to ambient PM pollution were estimated. RESULTS: A total of 104,779 CHD records were derived from 153 hospitals from these 9 cities. There were significant effects of PM pollution on hospital admissions (HAs) for CHD and specific CHD in Sichuan Province. A 10 µg/m3 increase of PM10 and PM2.5 was linked with a 0.46% (95% CI: 0.08, 0.84%), and 0.57% (95% CI: 0.05, 1.09%) increments in HAs for CHD at lag7, respectively. The health effects of air pollutants were comparable modified by age, season and gender, showing old (≥ 65 years) and in cold season being more vulnerable to the effects of ambient air pollution, while gender-specific effects is positive but not conclusive. Involving the WHO's air quality guidelines as the reference, 1784 and 2847 total cases of HAs for CHD could be attributable to PM10 and PM2.5, separately. The total medical cost that could be attributable to exceeding PM10 and PM2.5 were 42.04 and 67.25 million CNY from 2017 to 2018, respectively. CONCLUSIONS: This study suggested that the short-term exposure to air pollutants were associated with increased HAs for CHD in Sichuan Province, which could be implications for local environment improvement and policy reference.

Efficacy evaluation of PCSK9 monoclonal antibody (Evolocumab) in combination with Rosuvastatin and Ezetimibe on cholesterol levels in patients with coronary heart disease (CHD): A retrospective analysis from a single center in China.

BACKGROUND AND PURPOSE: Proprotein convertase subtilisin-kexin type 9(PCSK9) monoclonal antibody (Mab; Evolocumab) has been reported to inhibit low-density lipoprotein cholesterol (LDL-C) and Lipoprotein(a) [LP(a)] in coronary heart diseases (CHD) patients in America, Europe and Japan. However, little is known about the effect of Evolocumab in Chinese population. This retrospective study in Chinese CHD patients compared the efficacy without or with Evolocumab therapy added to the conventional treatment with a statin (Rosuvastatin) and a gut cholesterol absorption inhibitor (Ezetimibe). METHODS: CHD patients from our hospital were divided into three therapeutic groups, A) the statin monotherapy group (10 mg Rosuvastatin every night); B) the statin/cholesterol absorption inhibitor group (10 mg Rosuvastatin and 10 mg Ezetimibe daily); and C) the triple therapy with PCSK9 Mab group (10 mg Rosuvastatin daily, 10 mg Ezetimibe daily, and 140 mg Evolocumab once 2 weeks). The plasma lipid data were collected at 0, 4, 12, and 24 Week(s). The Graphpad Prism 7 program was used to perform all the statistical analysis. RESULTS: Out of 103 patients 91 were eligible for further evaluation with 31 in group A, 31 in group B, and 29 in group C. The plasma LDL-C levels were reduced only by 33.82% in the Rosuvastatin monotherapy group, 52.13% in the Rosuvastatin/Ezetimibe group, and 73.59% in the Evolocumab/Rosuvastatin/Ezetimibe group (P < 0.0001) at 24 weeks compared to the prior therapy levels. Neither the statin therapy alone (5.95%; P = 0.6), nor the double therapy (5.27%; P = 0.7) affected LP(a) levels. In contrast, addition of Evolocumab to the double therapy significantly decreased LP(a) level by 37.2% (P < 0.0001). CONCLUSION: Addition of Evolocumab to the standard double therapy in Chinese CHD patients improved the efficacy in LDL-C reduction when compared to Rosuvastatin alone or in Rosuvastatin/Ezetimibe double therapy. Furthermore, the addition of Evolocumab lowered LP(a) level in Chinese CHD patients.

The Therapeutic Effect and Mechanism of Qishen Yiqi Dripping Pills on Cardiovascular and Cerebrovascular Diseases and Diabetic Complications.

The alterations in vascular homeostasis are deeply involved in the development of numerous diseases, such as coronary heart disease, stroke, and diabetic complications. Changes in blood flow and endothelial permeability caused by vascular dysfunction are the common mechanisms for these three types of diseases. The disorders of glucose and lipid metabolism can bring changes in the energy production patterns in endothelium and surrounding cells which may consequently cause energy metabolic disorders, oxidative stress, and inflammatory responses. Traditional Chinese medicine (TCM) follows the principle of the "treatment by the syndrome differentiation." TCM considers coronary heart disease, stroke, and diabetes complications all as the type of Qi-deficiency and blood stasis syndrome, which mainly occurs in the vascular system. Therefore, the common pathogenesis of these three types of diseases suggests that the treatment strategy by TCM should be in a close manner and referred to as "treating different diseases by the same treatment." Qishen Yiqi dripping pill is a modern Chinese herbal medicine that has been widely used for the treatment of patients with coronary heart disease characterized as Qi-deficiency and blood stasis in China. Recently, many clinical reports have demonstrated the potential therapeutic effects of Qishen Yiqi dripping pills on ischemic stroke and diabetic nephropathy. Based on these reports, we will summarize the clinical applications of Qishen Yiqi dripping pills on coronary heart disease, ischemic stroke, and diabetic nephropathy, including the involved mechanisms discussed in various research works.

Long-term exposure to low-level ambient air pollution and incidence of stroke and coronary heart disease: a pooled analysis of six European cohorts within the ELAPSE project.

BACKGROUND: Long-term exposure to outdoor air pollution increases the risk of cardiovascular disease, but evidence is unclear on the health effects of exposure to pollutant concentrations lower than current EU and US standards and WHO guideline limits. Within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we investigated the associations of long-term exposures to fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and warm-season ozone (O3) with the incidence of stroke and acute coronary heart disease. METHODS: We did a pooled analysis of individual data from six population-based cohort studies within ELAPSE, from Sweden, Denmark, the Netherlands, and Germany (recruited 1992-2004), and harmonised individual and area-level variables between cohorts. Participants (all adults) were followed up until migration from the study area, death, or incident stroke or coronary heart disease, or end of follow-up (2011-15). Mean 2010 air pollution concentrations from centrally developed European-wide land use regression models were assigned to participants' baseline residential addresses. We used Cox proportional hazards models with increasing levels of covariate adjustment to investigate the association of air pollution exposure with incidence of stroke and coronary heart disease. We assessed the shape of the concentration-response function and did subset analyses of participants living at pollutant concentrations lower than predefined values. FINDINGS: From the pooled ELAPSE cohorts, data on 137 148 participants were analysed in our fully adjusted model. During a median follow-up of 17·2 years (IQR 13·8-19·5), we observed 6950 incident events of stroke and 10 071 incident events of coronary heart disease. Incidence of stroke was associated with PM2·5 (hazard ratio 1·10 [95% CI 1·01-1·21] per 5 µg/m3 increase), NO2 (1·08 [1·04-1·12] per 10 µg/m3 increase), and black carbon (1·06 [1·02-1·10] per 0·5 10-5/m increase), whereas coronary heart disease incidence was only associated with NO2 (1·04 [1·01-1·07]). Warm-season O3 was not associated with an increase in either outcome. Concentration-response curves indicated no evidence of a threshold below which air pollutant concentrations are not harmful for cardiovascular health. Effect estimates for PM2·5 and NO2 remained elevated even when restricting analyses to participants exposed to pollutant concentrations lower than the EU limit values of 25 µg/m3 for PM2·5 and 40 µg/m3 for NO2. INTERPRETATION: Long-term air pollution exposure was associated with incidence of stroke and coronary heart disease, even at pollutant concentrations lower than current limit values. FUNDING: Health Effects Institute.