Author + information
- Received July 15, 2018
- Revision received December 14, 2018
- Accepted December 18, 2018
- Published online April 22, 2019.
- Zhijing Lin, PhDa,∗,
- Renjie Chen, PhDa,∗,
- Yixuan Jiang, BAa,
- Yongjie Xia, PhDa,
- Yue Niu, PhDa,
- Cuiping Wang, PhDa,
- Cong Liu, PhDa,
- Chen Chen, MSa,
- Yihui Ge, MSa,
- Weidong Wang, MSa,
- Guanjin Yin, MSa,
- Jing Cai, PhDa,
- Viviane Clement, MSb,
- Xiaohui Xu, PhDb,
- Bo Chen, PhDa,
- Honglei Chen, PhDc and
- Haidong Kan, PhDa,d,∗∗ (, )@FudanUniversity
- aSchool of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, China
- bDepartment of Epidemiology and Biostatistics, School of Public Health, Texas A&M University, College Station, Texas
- cDepartment of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, Michigan
- dChildren's Hospital of Fudan University, National Center for Children's Health, Shanghai, China
- ↵∗Address for correspondence:
Dr. Haidong Kan, Department of Environmental Health, School of Public Health, Fudan University, P.O. Box 249, 130 Dong-An Road, Shanghai 200032, China.
Background Few studies have evaluated the health benefits of omega-3 fatty acid supplementation against fine particulate matter (aerodynamic diameter <2.5 μm [PM2.5]) exposure in highly polluted areas.
Objectives The authors sought to evaluate whether dietary fish-oil supplementation protects cardiovascular health against PM2.5 exposure in China.
Methods This is a randomized, double-blinded, and placebo-controlled trial among 65 healthy college students in Shanghai, China. Participants were randomly assigned to either the placebo group or the intervention group with dietary fish-oil supplementation of 2.5 g/day from September 2017 to January 2018, and received 4 rounds of health examinations in the last 2 months of treatments. Fixed-site PM2.5 concentrations on campus were measured in real time. The authors measured blood pressure and 18 biomarkers of systematic inflammation, coagulation, endothelial function, oxidative stress, antioxidant activity, cardiometabolism, and neuroendocrine stress response. Acute effects of PM2.5 on these outcomes were evaluated within each group using linear mixed-effect models.
Results The average PM2.5 level was 38 μg/m3 during the study period. Compared with the placebo group, the fish-oil group showed relatively stable levels of most biomarkers in response to changes in PM2.5 exposure. Between-group differences associated with PM2.5 exposure varied by biomarkers and by lags of exposure. The authors observed beneficial effects of fish-oil supplementation on 5 biomarkers of blood inflammation, coagulation, endothelial function, oxidative stress, and neuroendocrine stress response in the fish-oil group at a false discovery rate of <0.05.
Conclusions This trial shows that omega-3 fatty acid supplementation is associated with short-term subclinical cardiovascular benefits against PM2.5 exposure among healthy young adults in China. (Effect of Dietary Supplemental Fish Oil in Alleviating Health Hazards Associated With Air Pollution; NCT03255187)
Ambient air pollution is a ubiquitous public health problem. Epidemiological studies have demonstrated that both short-term and long-term exposures to fine particulate matter (aerodynamic diameter <2.5 μm [PM2.5]) air pollution were associated with increased cardiovascular morbidity and mortality (1,2). The Global Burden of Disease project estimated that 4.2 million premature deaths could be potentially attributable to ambient PM2.5 air pollution, and about 70% of these were cardiovascular deaths (3). The estimated public health burden is much higher in developing countries such as China and India because of their large population sizes and severities of air pollution.
In addition to efforts to improve the ambient air quality, personalized behavioral interventions may offer a practical way to mitigate some of the health hazards due to air pollution. We and other investigators have reported cardiovascular benefits of short-term use of indoor air purifiers (4) and particulate-filtering respirators (5,6). However, in many occasions, these exposure-lowering interventions are not readily available (e.g., outdoors) or appropriate (e.g., social interactions). Dietary supplementation may present another promising approach to mitigate the adverse effects from air pollution.
Although the exact pathophysiological mechanisms are yet to be fully understood, increased blood pressure (BP), systemic inflammation, coagulation, endothelial dysfunction, oxidative stress, insulin resistance and neuroendocrine disturbance are considered as main pathways or mechanisms whereby PM2.5 jeopardizes the cardiovascular health (1,7–10). It is therefore reasonable to speculate that measures targeting these biological pathways or mechanisms may offer cardiovascular benefits against PM2.5 air pollution. Fish oil is commonly used as a supplemental source of n-3 (also called omega−3) polyunsaturated fatty acids. Although current evidence does not support the use of omega-3 fatty acids supplementation in primary prevention or treatment of cardiovascular diseases (11,12), the American Heart Association recommends its use for secondary prevention of cardiovascular events in patients with coronary heart diseases and heart failure (11). Previous studies have suggested subclinical cardiovascular benefits derived from dietary supplementation with omega-3 fatty acids in stabilizing adverse cardiovascular biomarkers in both healthy adults and patients (11,13,14). Several studies further demonstrated potential cardiovascular benefits of omega-3 fatty acid supplementation against exposure to PM2.5 air pollution (15–19), but the evidence was mainly obtained either from chamber studies with concentrated PM2.5 or from real-world studies with limited outcomes examined (i.e., heart rate variability, platelet function, or selected oxidative stress biomarkers) in areas with low-to-moderate air pollution. We hereby conducted a randomized, double-blinded and placebo-controlled trial to evaluate whether omega-3 fatty acids supplementation offers cardiovascular benefits against the adverse effects of ambient PM2.5 exposure among healthy young adults in Shanghai, China.
Study participants and design
This trial was conducted between September 9, 2017, and January 13, 2018. We initially recruited 70 healthy college students on Fenglin campus of Fudan University in Shanghai, China. We excluded students who did not live on campus, or had a history of tobacco smoking or alcohol addiction, clinically diagnosed cardiovascular and respiratory diseases, or recent infections, or were allergic to omega-3 fatty acids or fish. Eligible participants were randomly assigned to receive dietary supplementation of either marine-derived fish oil (2.5 g/day) or placebo (sunflower-seed oil), and were monitored in a double-blinded fashion throughout the study period. We scheduled 4 rounds of follow-up visits with an interval of 2 weeks in the last 2 months of the intervention. To expand the daily variation range of PM2.5 exposures, in each round, we divided each group into 2 subgroups and arranged health examinations on either Saturday for the placebo group or Sunday for the fish-oil group at adjacent weeks. There were identical working conditions and technical procedures between these 2 assessment days. We collected data on individual characteristics (i.e., age, sex, height, and weight), time–location information, and physical activity at baseline and during the follow-ups. We also asked participants to complete a food frequency questionnaire at the start, middle, and end of the study, which was modified from previously used questionnaires that had been developed to adapt to the Chinese dietary pattern (20–22). We hereby assessed dietary intakes of nutrients over the past 2 months by combining the recoded consumption frequencies and portion sizes of 133 food items (categorized into 25 food groups) and the Chinese food composition table (Supplemental Methods in the Online Appendix). The results of validation work conducted before the start of the study showed our questionnaire had good validity and reproducibility (Online Table 1).
This study protocol was registered at ClinicalTrials.gov (NCT03255187) and was approved by the Institutional Review Board of the School of Public Health, Fudan University. All participants provided written informed consent at enrollment.
Participants in the intervention group were instructed to take 2 capsules (1.25 g each) of marine-derived fish oil every day throughout the study period. Each 1.25-g capsule contained 60% of omega-3 fatty acids (36% eicosapentaenoic acid [EPA] and 24% docosahexaenoic acid [DHA]). Participants in the placebo group received 2 capsules of sunflower-seed oil every day, which had an identical appearance with the fish-oil capsule. Each placebo capsule contained 14.4% palmitic acid (C16:0), 16.0% oleic acid (C18:1 n-9), and 57.6% linoleic acid (C18:2 n-6). The participants and study staff were blinded to which group contained which participants. We assessed compliance to intervention by measuring the whole-blood concentrations of DHA, EPA, and oleic acid at baseline and follow-ups, and provided details the Online Appendix.
To obtain real-time measurements of ambient PM2.5 concentrations, we installed an Environmental Dust Monitor (GRIMM Aerosol Technik Ainring, Ainring, Germany) on the rooftop of a 10-m-high building in the center of Fenglin campus. To account for gaseous pollutants, we derived hourly data of sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone from a fixed-site air quality monitor that was about 3.5 km away from the campus. Temperature and relative humidity were recorded at the individual level using temperature/relative humidity data loggers (HOBO UX100-003, Onset Computer, Bourne, Massachusetts).
At each round of health examinations, we measured BP and collected fasting blood samples at 8:00 to 9:00 am to minimize potential influences from circadian rhythms, as detailed in Supplemental Methods of the Online Appendix.
We measured serum levels of a range of circulating biomarkers that have shown associations with cardiovascular health in previous studies (9,10,23–28). We evaluated: 1) 3 biomarkers of systemic inﬂammation, including high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α (23); 2) 2 biomarkers of coagulation, including von Willebrand factor (vWF) and fibrinogen (24); 3) 3 biomarkers of endothelial function, including endothelin-1, E-selectin, and endothelial nitric oxide synthase (eNOS) (25,26); 4) 2 biomarkers of systemic oxidative stress, including oxidized low-density lipoprotein (ox-LDL) and lipid peroxidation (27); 5) 3 biomarkers of antioxidant activity, including total antioxidant capacity, glutathione peroxidase, and superoxide dismutase (28); 6) insulin resistance, calculated by fasting glucose and fasting insulin using the formula of (fasting insulin [mU/l] × fasting glucose [mmol/l])/22.5 (10); and 7) 4 neuroendocrine stress hormones, including corticotropin releasing hormone, adrenocorticotropic hormone, cortisol, and serotonin (9). Detailed methods of these chemical assays are provided in the Online Appendix.
Environmental and health data were linked by the time of blood drawn (rounded to the integer hour). Blood pressure was directly used because it was normally distributed; other outcome variables were log-transformed because they followed a log-normal distribution.
We used linear mixed-effects models to evaluate short-term exposure to PM2.5 in relation to each of cardiovascular outcomes within each treatment group. In the basic model, we included PM2.5 as a fixed-effect independent term, and added a random-effect intercept for each subject to account for correlations among repeated measurements per person, assuming a compound symmetry covariance structure. We further adjusted for age, sex, body mass index (weight/height2), 3-day average temperature, and 3-day average relative humidity. We did not adjust for time trends because all 4 health visits were completed within a short period of 2 months. To explore the lag patterns that the acute effects of PM2.5 might have on individual biomarkers, we applied multiple averaging periods preceding the blood drawn, that is, 0 to 6 h, 0 to 12 h, 0 to 24 h, and 0 to 48 h. We further tested the statistical differences between the 2 treatment groups in their effect estimates of PM2.5 on individual biomarkers and calculated the 95% confidence intervals (CI) as:
where and are the effect estimates of PM2.5 for the 2 treatment groups, and and are their respective standard errors. In addition, we assessed whether insulin resistance modified the associations of PM2.5 with biomarkers in each group by adding an interaction term between PM2.5 and insulin resistance to the basic models.
To test the robustness of our results, we performed 3 sensitivity analyses. First, we repeated analyses by fitting 2-pollutant models by adding the present-day concentrations of 4 gaseous pollutants to regression models 1 at a time. Second, in the basic models, we further adjusted for baseline dietary intakes of nutrients that were significantly different between the 2 groups. Finally, we repeated regression analyses with log-transformed PM2.5 concentrations instead of the direct PM2.5 data. To explore the possibly diminishing effects of PM2.5, we applied longer lag periods (i.e., 0 to 72 h and 0 to 96 h) in supplementary analyses. To examine potential side effects of oleic acid in the placebo group, we analyzed blood oleic acid in relation to the aforementioned cardiovascular outcomes using the basic models.
All analyses were conducted using the “lme4” package of R software version 3.3.1 (R Foundation for Statistical Computing, Vienna, Austria). We used the Benjamini-Hochberg false discovery rate (FDR) to account for multiple comparisons in examining between-group differences, using a FDR <0.05 considered as the cutoff for statistical significance. In the within-treatment group analyses, we presented the percentage changes in biomarkers and their 95% CIs for each 10-μg/m3 increment in PM2.5 exposure, and presented the absolute changes in BP (in mm Hg) and their 95% CIs for each 10-μg/m3 increment in PM2.5 exposure. To demonstrate potential benefits of fish-oil supplementation, we presented differences in the effect sizes of the PM2.5–biomarker associations between the fish-oil and placebo groups.
A total of 65 of 70 eligible participants completed the scheduled follow-ups (Online Figure 1). Only 2 participants were examined on a different date than the scheduled one in 2 rounds of health examinations. The 2 groups were similar at enrollment in the distribution of age, sex, body mass index, time spent in indoors versus outdoors, physical activity levels, BP, and cardiovascular biomarkers (Online Table 2).
Table 1 summarizes the descriptive statistics of PM2.5 concentrations, temperature, and relative humidity. The average PM2.5 level is 38 μg/m3 during the study period. At the individual level, the 3-day averaged temperature and humidity were 20°C and 46%, respectively. The concentrations of gaseous pollutants are provided in Online Table 3.
There were no statistically significant differences in baseline dietary intake of nutrients other than heptadecanoic acid (C17:0) and heptadecenoic acid (C17:1) (Online Table 4), which were adjusted for in subsequent sensitivity analyses. The 2 groups also reported similar dietary intakes of omega-3 fatty acids throughout the study period (Online Table 5). Although the 2 groups had similar blood levels of DHA and EPA at baseline, the fish-oil group showed substantially higher levels of both EPA and DHA than the placebo group during follow-up (Online Table 6), indicating good compliance with treatments.
Compared with the placebo group, the fish-oil group showed an overall biomarker profile that indicates better cardiovascular health (Online Figure 2). For example, the mean levels of high-sensitivity C-reactive protein that have a negative implication for cardiovascular health were consistently lower in the fish-oil group and the mean levels of glutathione peroxidase that have a positive implication for cardiovascular health were consistently higher in the fish-oil group during the follow-ups.
Overall, in the placebo group, most biomarkers of cardiovascular health tended to significantly respond to PM2.5 fluctuations during the study period; however, in the fish-oil group, the associations became much weaker and statistically insignificant. The magnitude and statistical significance of between-group differences in these associations, however, varied by biomarkers and by lags of exposure.
PM2.5 was not associated with BP in either treatment group, nor was there a significant between-group difference (Online Table 7).
Biomarkers of inflammation
PM2.5 level was significantly associated with 3 biomarkers of systemic inflammation (C-reactive protein, interleukin-6, and tumor necrosis factor-α) in the placebo group, but not in the fish-oil group (Figure 1). Significant between-group difference was only observed for interleukin-6. Compared with the placebo group, for each 10-μg/m3 increase in PM2.5, the increment of interleukin-6 concentration was 32.68% smaller (95% CI: 14.73% to 50.64%; FDR <0.001) in the fish-oil group in the 24-h-lag analysis and 33.47% smaller (95% CI: 14.43% to 52.51%; FDR = 0.002) in the 48-h-lag analysis.
Biomarkers of coagulation
Similar observations were also made for 2 biomarkers of coagulation: vWF and fibrinogen were both associated with PM2.5 level only in the placebo group, not in the fish-oil group (Figure 2). A significant between-group difference was only observed for vWF. Compared with the placebo group, fish-oil supplementation led to an 8.15% lower estimate (95% CI: 2.00% to 14.29%; FDR = 0.047) in vWF concentration (lag 48 h) for each 10-μg/m3 increase in PM2.5.
Biomarkers of endothelial function
As shown in Figure 3, higher PM2.5 exposure was associated with higher levels of endothelin-1 and E-selectin, and a lower concentration of serum eNOS protein, again only in the placebo group. The significant between-group difference was only observed for E-selectin. Compared with the placebo group, fish-oil supplementation led to a 9.41% (95% CI: 2.61% to 16.22%; FDR = 0.047) decrease in the percentage estimate of E-selectin (lag 6 h) per 10-μg/m3 increase in PM2.5.
Biomarkers of oxidative stress
Again, only in the placebo group, higher PM2.5 exposure was associated with a higher level of ox-LDL and lower activities of total antioxidant capacity, glutathione peroxidase, and superoxide dismutase, consistent with a profile of oxidative stress (Figure 4). A significant between-group difference was only present for ox-LDL. Compared with the placebo group, fish-oil supplementation resulted in a decrease of 9.39% (95% CI: 3.29% to 15.50%; FDR = 0.047) in the percentage estimate of ox-LDL (lag 6 h) in response to a 10-μg/m3 increase in PM2.5.
Similar observations were also made for stress hormones (Figure 5). In the placebo group, PM2.5 exposure was positively associated with levels of corticotropin releasing hormone, adrenocorticotropic hormone, and cortisol, and inversely with serotonin level. A significant between-group difference was only observed for cortisol. Compared with the placebo group, fish-oil supplementation resulted in a decrease of 13.43% (95% CI: 6.12% to 20.74%; FDR <0.001) in the percentage estimate of cortisol (lag 48 h) for each 10-μg/m3 increase in PM2.5.
Figure 5 also shows a significant association of PM2.5 with insulin resistance in the placebo group, but not in the fish-oil group. Between-group differences, however, were not statistically significant.
Accordingly, we summarize in the Central Illustration the largest between-group differences among lags of exposure in the percentage changes of cardiovascular biomarkers associated with a 10-μg/m3 increase in PM2.5 comparing the fish-oil group to the placebo group.
In the 2-pollutant model analyses, our main ﬁndings were relatively robust to the adjustment for simultaneous exposure to ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide (Online Tables 8 to 11). Further, the results were barely changed after adjusting for baseline dietary intakes of heptadecanoic acid (C17:0) and heptadecenoic acid (C17:1), the only 2 nutrients that showed between-group differences at enrollment (Online Tables 12 and 13). Finally, the third sensitivity analysis with log-transformed PM2.5 showed similar, but not identical, results to the original observations (Online Figure 3), but these differences did not change the study conclusions.
In addition, with longer lags, the observations became less apparent and eventually disappeared at 96 h (Online Table 14). We did not see effect modifications of insulin resistance on the associations between PM2.5 and individual outcomes in either group (Online Table 15). Finally, whole-blood oleic acid was not associated with any cardiovascular outcomes in either group, nor did we observe any between-group differences (Online Table 16).
In this randomized trial among healthy young adults in Shanghai, China, we examined the potential cardiovascular benefits of fish-oil supplementation against ambient PM2.5 exposure. We measured a wide range of biomarkers of cardiovascular health in response to short-term exposure to PM2.5, and found protective effects of fish-oil supplementation on ameliorating biomarkers of inflammation, coagulation, endothelial dysfunction, oxidative stress, and neuroendocrine disturbance.
Inflammation and thrombosis are considered 2 of the most important mechanisms in mediating the adverse cardiovascular effects of PM2.5 (1). In our study, multiple biomarkers of inflammation and thrombosis were associated with PM2.5 concentrations in the placebo group, but not in the fish-oil group. Further, between-group analyses demonstrated that omega-3 fatty acids supplementation leads to significantly stabilized interleukin-6 and vWF concentrations in response to PM2.5 fluctuation. Such potential anti-inflammatory and attenuation of the prothrombotic effect of omega-3 fatty acids against PM2.5 are supported by in vitro and in vivo experimental studies (29–31). However, a prior chamber study among healthy middle-aged adults did not observe such benefits when participants were exposed to high levels of PM2.5 (18). The study, however, had 29 participants and 4 weeks of supplementation, which might not provide sufficient power to demonstrate any potential benefits. These benefits of omega-3 fatty acids may be mediated through multiple mechanisms, for example, serving as eicosanoid substrates to inhibit arachidonic acid metabolism, deriving potent anti-inflammatory mediators (e.g., resolvins and protectins), suppressing the expression of inflammatory genes, and inhibiting platelet aggregation and fibrinolysis (32,33).
Endothelial dysfunction represents another important pathophysiological mechanism of how air pollutants jeopardize cardiovascular health (1). In our study, omega-3 fatty acid supplementation was associated with a significant decrease in E-selectin (a marker of endothelial cell activation and neutrophil adhesion) and an insignificant increase of eNOS (a marker of vasodilation) in response to higher PM2.5 exposure, indicating better endothelial function. Mechanistically, omega-3 fatty acids can inhibit the recruitment of neutrophils and monocytes to the endothelium by modulating the expression of endothelial vasoconstrictors such as E-selectin, a key adhesion molecule directly mediating angiogenesis and endothelial proliferation (34). Further, omega-3 fatty acids can simultaneously enhance the production and bioavailability of endothelium-derived relaxing factor (i.e., nitric oxide) by modulating eNOS, a primary controller of cardiovascular smooth muscle tone (13,35).
In addition, our study suggests that omega-3 fatty acids supplementation may attenuate oxidative stress induced by PM2.5 exposure, probably by promoting antioxidant activity and reducing response to oxidative stress. Our findings are consistent with those from a previous clinical trial conducted among older adults (17). Further, prior experiments in rodents and cultured cells showed that omega-3 fatty acids significantly increased glutathione peroxidase and superoxide dismutase activities in response to PM2.5 exposure, accompanied by reduced levels of malondialdehyde, a marker of lipid peroxidation (29,30). This protective effect is biologically plausible, given that DHA and EPA directly reduce generation of reactive oxygen species through alteration of mitochondrial reactive oxygen species and nicotinamide adenine dinucleotide phosphate-oxidase activity (36).
We recently reported that PM2.5 might also contribute to cardiovascular diseases by activating the hypothalamus–pituitary–adrenal axis (9). The current study suggests that omega-3 fatty acid supplementation may reduce the release of stress hormones (especially cortisol) in response to PM2.5 exposure. This observation is also consistent with a previous study that showed reduced cortisol levels following omega-3 fatty acid supplementation among healthy participants (37). Taken together, our findings provide initial evidence that omega-3 fatty acid supplementation alleviates neuroendocrine stress responses to ambient PM2.5 exposure, which may mitigate its adverse effects on cardiovascular outcomes.
Our study has several strengths. First, this randomized, double-blinded, placebo-controlled trial design allows direct causal inference, which is logistically facilitated by recruiting healthy college students to ensure relative homogeneity in study participation, treatment adherence, and population characteristics. Second, the current study was conducted in a free-living population over a reasonably long period rather than in an exposure-controlled environment, making study findings more generalizable to real-world situations. Finally, we analyzed a wide variety of biomarkers that have been implicated as mechanistic markers that mediate cardiovascular risk due to high PM2.5 exposure. This has allowed us to comprehensively assess the potential beneﬁts of omega-3 fatty acids supplementation against PM2.5-induced cardiovascular risks and relevant biological mechanisms.
First, we did not have personal data on PM2.5 exposures, rather we estimated exposures on the basis of an outdoor monitor on campus. However, fixed-site monitoring data has been shown to serve as a good surrogate for personal PM2.5 exposure in previous longitudinal studies (38), and we have no reason to believe the measurement errors are different in the 2 intervention groups. Second, we conducted the study among healthy college students for logistic considerations. Compared with at-risk populations (e.g., older adults), they may be less susceptible to the adverse effects of PM2.5 and conversely to the benefits of omega-3 fatty acids supplementation. For this reason, we chose to focus on subclinical biomarkers of cardiovascular health rather than direct clinical or functional measures (e.g., heart rate variability and flow-mediated dilatation). Future studies should target more susceptible populations and use more clinically meaningful measures. Finally, although we recorded the profile of routine dietary nutrients intake by food frequency questionnaire, we cannot exclude the confounding effects from daily dietary intakes of omega-3 fatty acids and other nutrients. However, because these randomly grouped healthy volunteers typically have a regular diet at the university cafeteria, and adjustment of the roughly estimated daily dietary intakes do not significantly change our results, this potential confounding might not be substantial.
This interventional study suggests that dietary omega-3 fatty acids supplementation may have short-term benefits in mitigating potential adverse cardiovascular effects in response to higher levels of PM2.5. In areas with relatively heavy air pollution, supplementation with omega-3 fatty acids may represent a simple and effective way to protect cardiovascular health against hazardous exposure to ambient PM2.5.
COMPETENCY IN MEDICAL KNOWLEDGE: Omega-3 fatty acid supplementation is associated with beneficial changes in cardiovascular biomarkers among healthy young adults, suggesting potential cardiovascular protection from exposure to fine particulate atmospheric pollution.
TRANSLATIONAL OUTLOOK: Prospective trials are needed to confirm the results of this study and assess whether fish-oil supplementation can reduce cardiovascular risk in vulnerable populations exposed to severe air pollution.
The authors appreciate the contributions of all volunteers in this study.
↵∗ Drs. Lin and R. Chen contributed equally to this work.
Dr. Renjie Chen was supported by the National Natural Science Foundation of China (91743111). Dr. Haidong Kan was supported by the National Natural Science Foundation of China (91843302 and 91643205) and China Medical Board Collaborating Program (16-250). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Abbreviations and Acronyms
- blood pressure
- confidence interval
- docosahexaenoic acid
- endothelial nitric oxide synthase
- eicosapentaenoic acid
- false discovery rate
- oxidized low-density lipoprotein
- particulate matter with an aerodynamic diameter <2.5 μm
- von Willebrand factor
- Received July 15, 2018.
- Revision received December 14, 2018.
- Accepted December 18, 2018.
- 2019 American College of Cardiology Foundation
- Brook R.D.,
- Rajagopalan S.,
- Pope C.A. 3rd.,
- et al.
- GBD 2015 Risk Factors Collaborators
- Chen R.J.,
- Zhao A.,
- Chen H.L.,
- et al.
- Shi J.,
- Lin Z.,
- Chen R.,
- et al.
- Pope C.A.,
- Bhatnagar A.,
- McCracken J.P.,
- Abplanalp W.,
- Conklin D.J.,
- O'Toole T.
- Li H.,
- Cai J.,
- Chen R.,
- et al.
- Chen Z.H.,
- Salam M.T.,
- Toledo-Corral C.,
- et al.
- Siscovick D.S.,
- Barringer T.A.,
- Fretts A.M.,
- et al.
- Tong H.,
- Rappold A.G.,
- Caughey M.,
- et al.
- Becerra A.Z.,
- Georas S.,
- Brenna J.T.,
- et al.
- Whitton C.,
- Ho J.C.Y.,
- Tay Z.,
- et al.
- Hong X.,
- Ye Q.,
- Wang Z.Y.,
- et al.
- Shu L.,
- Zheng P.F.,
- Zhang X.Y.,
- et al.
- Yoon Y.,
- Song J.,
- Hong S.H.,
- Kim J.Q.
- Hulsmann M.,
- Stanek B.,
- Frey B.,
- et al.
- Du X.,
- Jiang S.,
- Bo L.,
- et al.
- Li X.Y.,
- Hao L.,
- Liu Y.H.,
- Chen C.Y.,
- Pai V.J.,
- Kang J.X.
- Mozaffarian D.,
- Wu J.H.
- Peter S.,
- Holguin F.,
- Wood L.G.,
- et al.
- Chen C.,
- Cai J.,
- Wang C.C.,
- et al.