Racial/Ethnic Discrimination and Cardiometabolic Diseases: A Systematic Review.

INTRODUCTION: Racial discrimination has been identified as a risk factor for cardiometabolic diseases, the leading cause of morbidity and mortality among racial/ethnic minority groups; however, there is no synthesis of current knowledge on the association between discrimination and cardiometabolic diseases. The objective of this systematic review was to summarize evidence linking racial/ethnic discrimination and cardiometabolic diseases. METHODS: The review was conducted based on studies identified via electronic searches of 5 databases (PubMed, Google Scholar, WorldWideScience.org, ResearchGate and Microsoft Academic) using terms related to discrimination and cardiometabolic disease. RESULTS: Of the 123 eligible studies included in the review, 87 were cross-sectional, 25 longitudinal, 8 quasi-experimental, 2 randomized controlled trials and 1 case-control. Cardiometabolic disease outcomes discussed were hypertension (n = 46), cardiovascular disease (n = 40), obesity (n = 12), diabetes (n = 11), metabolic syndrome (n = 9), and chronic kidney disease (n = 5). Although a variety of discrimination measures was employed across the studies, the Everyday Discrimination Scale was used most often (32.5%). African Americans/Blacks were the most frequently studied racial/ethnic group (53.1%), and American Indians the least (0.02%). Significant associations between racial/ethnic discrimination and cardiometabolic disease were found in 73.2% of the studies. DISCUSSION: Racial/ethnic discrimination is positively associated with increased risk of cardiometabolic disease and higher levels of cardiometabolic biomarkers. Identifying racial/ethnic discrimination as a potential key contributor to the health inequities associated with cardiometabolic diseases is important for addressing the significant burden borne by racial/ethnic minorities.

Exposure to Volatile Organic Compounds Is Associated with Hypertension in Black Adults: The Jackson Heart Study.

BACKGROUND: The prevalence of hypertension is higher among Black adults than among White and Hispanic adults. Nevertheless, reasons underlying the higher rates of hypertension in the Black population remain unclear but may relate to exposure to environmental chemicals such as volatile organic compounds (VOCs). METHODS: We evaluated the associations of blood pressure (BP) and hypertension with VOC exposure in non-smokers and smokers in a subgroup of the Jackson Heart Study (JHS), consisting of 778 never smokers and 416 age- and sex-matched current smokers. We measured urinary metabolites of 17 VOCs by mass spectrometry. RESULTS: After adjusting for covariates, we found that amoong non-smokers, metabolites of acrolein and crotonaldehyde were associated with a 1.6 mm Hg (95%CI: 0.4, 2.7; p = 0.007) and a 0.8 mm Hg (95%CI: 0.01, 1.6; p = 0.049) higher systolic BP, and the styrene metabolite was associated with a 0.4 mm Hg (95%CI: 0.09, 0.8, p = 0.02) higher diastolic BP. Current smokers had 2.8 mm Hg (95% CI 0.5, 5.1) higher systolic BP. They were at higher risk of hypertension (relative risk = 1.2; 95% CI, 1.1, 1.4), and had higher urinary levels of several VOC metabolites. Individuals who smoke had higher levels of the urinary metabolites of acrolein, 1,3-butadiene, and crotonaldehyde and were associated with higher systolic BP. The associations were stronger among participants who were <60 years of age and male. Using Bayesian kernel machine regression to assess the effects of multiple VOC exposures, we found that the relationship between VOCs and hypertension among non-smokers was driven primarily by acrolein and styrene in non-smokers, and crotonaldehyde in smokers. CONCLUSIONS: Hypertension in Black individuals may be attributed, in part, to VOC exposure from the environment or tobacco smoke.

Residential proximity to greenness mitigates the hemodynamic effects of ambient air pollution.

Residential proximity to greenness is associated with a lower risk of cardiovascular disease (CVD) and all-cause mortality. However, it is unclear whether the beneficial effects of greenness are linked to a reduction in the effects of ambient air pollutants. We measured arterial stiffness in 73 participants with moderate to high CVD risk. Average levels of ambient PM2.5 and ozone were calculated from local monitoring stations. Residential greenness was estimated using satellite-derived normalized difference vegetation index (NDVI) for a 200-m and 1-km radius around each participant's home. Participants were 51% female, average age of 52 yr, and 79% had diagnosed hypertension. In multiple linear regression models, residential NDVI was negatively associated with augmentation index (-3.8% per 0.1 NDVI). Ambient levels of PM2.5 [per interquartile range (IQR) of 6.9 µg/m3] were positively associated with augmentation pressure (3.1 mmHg), pulse pressure (5.9 mmHg), and aortic systolic pressure (8.1 mmHg). Ozone (per IQR of 0.03 ppm) was positively associated with augmentation index (5.5%), augmentation pressure (3.1 mmHg), and aortic systolic pressure (10 mmHg). In areas of low greenness, both PM2.5 and ozone were positively associated with pulse pressure. Additionally, ozone was positively associated with augmentation pressure and systolic blood pressure. However, in areas of high greenness, there was no significant association between indices of arterial stiffness with either PM2.5 or ozone. Residential proximity to greenness is associated with lower values of arterial stiffness. Residential greenness may mitigate the adverse effects of PM2.5 and ozone on arterial stiffness.NEW & NOTEWORTHY Previous studies have linked proximity to green spaces with lower cardiovascular disease risk. However, the mechanisms underlying the salutary effects of green areas are not known. In our study of participants at risk of cardiovascular disease, we found that arterial stiffness was positively associated with short-term exposure to PM2.5, PM10, and ozone and inversely associated with greenness. The association between pollution and arterial stiffness was attenuated in areas of high greenness, suggesting that living green neighborhoods can lessen the adverse cardiovascular effects of air pollution.

Association between residential greenness and exposure to volatile organic compounds.

Residential proximity to vegetation and plants is associated with many health benefits, including reduced risk of cardiovascular disease, diabetes and mental stress. Although the mechanisms by which proximity to greenness affects health remain unclear, plants have been shown to remove particulate air pollution. However, the association between residential-area vegetation and exposure to volatile organic chemicals (VOCs) has not been investigated. We recruited a cohort of 213 non-smoking individuals and estimated peak, cumulative, and contemporaneous greenery using satellite-derived normalized difference vegetation index (NDVI) near their residence. We found that the urinary metabolites of exposure to VOCs - acrolein, acrylamide, acrylonitrile, benzene, 1-bromopropane, propylene oxide were inversely associated (7-31% lower) with 0.1 higher peak NDVI values within 100 m radius of the participants' home. These associations were significant at radii ranging from 25 to 300 m. Strongest associations were observed within a 200 m radius, where VOC metabolites were 22% lower per 0.1 unit higher NDVI. Of the 18 measured urinary metabolites, 7 were positively associated with variation of greenness within a 200 m radius of homes. The percent of tree canopy and street trees around participants' residence were less strongly associated with metabolite levels. The associations between urinary VOC metabolites and residential NDVI values were stronger in winter than in summer, and in participants who were more educated, White, and those who lived close to areas of high traffic. These findings suggest high levels of residential greenness are associated with lower VOC exposure, particularly in winter.

Association Between Residential Greenness and Cardiovascular Disease Risk.

Background Exposure to green vegetation has been linked to positive health, but the pathophysiological processes affected by exposure to vegetation remain unclear. To study the relationship between greenness and cardiovascular disease, we examined the association between residential greenness and biomarkers of cardiovascular injury and disease risk in susceptible individuals. Methods and Results In this cross-sectional study of 408 individuals recruited from a preventive cardiology clinic, we measured biomarkers of cardiovascular injury and risk in participant blood and urine. We estimated greenness from satellite-derived normalized difference vegetation index ( NDVI ) in zones with radii of 250 m and 1 km surrounding the participants' residences. We used generalized estimating equations to examine associations between greenness and cardiovascular disease biomarkers. We adjusted for residential clustering, demographic, clinical, and environmental variables. In fully adjusted models, contemporaneous NDVI within 250 m of participant residence was inversely associated with urinary levels of epinephrine (-6.9%; 95% confidence interval, -11.5, -2.0/0.1 NDVI ) and F2-isoprostane (-9.0%; 95% confidence interval, -15.1, -2.5/0.1 NDVI ). We found stronger associations between NDVI and urinary epinephrine in women, those not on ß-blockers, and those who had not previously experienced a myocardial infarction. Of the 15 subtypes of circulating angiogenic cells examined, 11 were inversely associated (8.0-15.6% decrease/0.1 NDVI ), whereas 2 were positively associated (37.6-45.8% increase/0.1 NDVI ) with contemporaneous NDVI . Conclusions Independent of age, sex, race, smoking status, neighborhood deprivation, statin use, and roadway exposure, residential greenness is associated with lower levels of sympathetic activation, reduced oxidative stress, and higher angiogenic capacity.

Benzene exposure is associated with cardiovascular disease risk.

Benzene is a ubiquitous, volatile pollutant present at high concentrations in toxins (e.g. tobacco smoke) known to increase cardiovascular disease (CVD) risk. Despite its prevalence, the cardiovascular effects of benzene have rarely been studied. Hence, we examined whether exposure to benzene is associated with increased CVD risk. The effects of benzene exposure in mice were assessed by direct inhalation, while the effects of benzene exposure in humans was assessed in 210 individuals with mild to high CVD risk by measuring urinary levels of the benzene metabolite trans,trans-muconic acid (t,t-MA). Generalized linear models were used to assess the association between benzene exposure and CVD risk. Mice inhaling volatile benzene had significantly reduced levels of circulating angiogenic cells (Flk-1+/Sca-1+) as well as an increased levels of plasma low-density lipoprotein (LDL) compared with control mice breathing filtered air. In the human cohort, urinary levels of t,t-MA were inversely associated several populations of circulating angiogenic cells (CD31+/34+/45+, CD31+/34+/45+/AC133-, CD34+/45+/AC133+). Although t,t-MA was not associated with plasma markers of inflammation or thrombosis, t,t-MA levels were higher in smokers and in individuals with dyslipidemia. In smokers, t,t-MA levels were positively associated with urinary metabolites of nicotine (cotinine) and acrolein (3-hydroxymercapturic acid). Levels of t,t-MA were also associated with CVD risk as assessed using the Framingham Risk Score and this association was independent of smoking. Thus, benzene exposure is associated with increased CVD risk and deficits in circulating angiogenic cells in both smokers and non-smokers.

Residential Proximity to Major Roadways Is Associated With Increased Levels of AC133+ Circulating Angiogenic Cells.

OBJECTIVES: Previous studies have shown that residential proximity to a roadway is associated with increased cardiovascular disease risk. Yet, the nature of this association remains unclear, and its effect on individual cardiovascular disease risk factors has not been assessed. The objective of this study was to determine whether residential proximity to roadways influences systemic inflammation and the levels of circulating angiogenic cells. APPROACH AND RESULTS: In a cross-sectional study, cardiovascular disease risk factors, blood levels of C-reactive protein, and 15 antigenically defined circulating angiogenic cell populations were measured in participants (n=316) with moderate-to-high cardiovascular disease risk. Attributes of roadways surrounding residential locations were assessed using geographic information systems. Associations between road proximity and cardiovascular indices were analyzed using generalized linear models. Close proximity (<50 m) to a major roadway was associated with lower income and higher rates of smoking but not C-reactive protein levels. After adjustment for potential confounders, the levels of circulating angiogenic cells in peripheral blood were significantly elevated in people living in close proximity to a major roadway (CD31(+)/AC133(+), AC133(+), CD34(+)/AC133(+), and CD34(+)/45(dim)/AC133(+) cells) and positively associated with road segment distance (CD31(+)/AC133(+), AC133(+), and CD34(+)/AC133(+) cells), traffic intensity (CD31(+)/AC133(+) and AC133(+) cells), and distance-weighted traffic intensity (CD31(+)/34(+)/45(+)/AC133(+) cells). CONCLUSIONS: Living close to a major roadway is associated with elevated levels of circulating cells positive for the early stem marker AC133(+). This may reflect an increased need for vascular repair. Levels of these cells in peripheral blood may be a sensitive index of cardiovascular injury because of residential proximity to roadways.

Acrolein exposure is associated with increased cardiovascular disease risk.

BACKGROUND: Acrolein is a reactive aldehyde present in high amounts in coal, wood, paper, and tobacco smoke. It is also generated endogenously by lipid peroxidation and the oxidation of amino acids by myeloperoxidase. In animals, acrolein exposure is associated with the suppression of circulating progenitor cells and increases in thrombosis and atherogenesis. The purpose of this study was to determine whether acrolein exposure in humans is also associated with increased cardiovascular disease (CVD) risk. METHODS AND RESULTS: Acrolein exposure was assessed in 211 participants of the Louisville Healthy Heart Study with moderate to high (CVD) risk by measuring the urinary levels of the major acrolein metabolite-3-hydroxypropylmercapturic acid (3-HPMA). Generalized linear models were used to assess the association between acrolein exposure and parameters of CVD risk, and adjusted for potential demographic confounders. Urinary 3-HPMA levels were higher in smokers than nonsmokers and were positively correlated with urinary cotinine levels. Urinary 3-HPMA levels were inversely related to levels of both early (AC133(+)) and late (AC133(-)) circulating angiogenic cells. In smokers as well as nonsmokers, 3-HPMA levels were positively associated with both increased levels of platelet-leukocyte aggregates and the Framingham Risk Score. No association was observed between 3-HPMA and plasma fibrinogen. Levels of C-reactive protein were associated with 3-HPMA levels in nonsmokers only. CONCLUSIONS: Regardless of its source, acrolein exposure is associated with platelet activation and suppression of circulating angiogenic cell levels, as well as increased CVD risk.

Tumor necrosis factor-α mediates interactions between macrophages and epithelial cells underlying proinflammatory gene expression induced by particulate matter.

Ambient particulate matter (PM) exposure is known to have adverse effects on respiratory health, but the underlying mechanisms remain obscure. We tested the hypothesis that macrophages and epithelial cells synergize to produce maximal cytokine release in response to PM exposure, thereby promoting inflammatory responses. We developed a co-culture model using MLE-12 (mouse lung epithelial) cells and RAW 264.7 (mouse monocyte/macrophage) cells. MLE-12 cells produced KC (Cxcl1) but not tumor necrosis factor-α (TNF), and KC was upregulated only at high levels of urban particulate matter (UPM; NIST 1648a). RAW 264.7 cells produced TNF but not KC, and TNF production was increased by treatment with UPM. In contrast, KC production was upregulated by co-culture of MLE-12 and RAW 264.7 cells, and it was further increased by treatment with a concentration of UPM that had no effect on MLE-12 cells alone. Multiplex cytokine assay revealed a similar pattern of synergistic production of MIG (Cxcl9) and IP-10 (Cxcl10) in co-cultures in response to UPM. TNF was implicated as mediating the synergistic increase in KC production because TNF upregulated KC production in MLE-12 cells, and UPM-induced KC production in co-cultures could be inhibited by a TNF blocking antibody. Intratracheal instillation of UPM into both wild-type and TNF receptor knockout mice resulted in increased TNF production in lavage fluid and increased TNF mRNA expression in cells recovered from lavage fluid. Additionally, UPM instillation into wild-type mice resulted in increased neutrophils and KC in lavage fluid, and these were inhibited in UPM-exposed TNF receptor knockout mice. These results are consistent with a model in which PM activates TNF production in macrophages which in turn stimulates epithelial cells to produce proinflammatory cytokines such as KC. The findings suggest a potential mechanism by which inhaled PM induces inflammation in the lung.