Faculty Bibliography

Environmental stressors associated with human activities (eg, air and noise pollution, light disturbance at night) and climate change (eg, heat, wildfires, extreme weather events) are increasingly recognized as contributing to cardiovascular morbidity and mortality. These harmful exposures have been shown to elicit changes in stress responses, circadian rhythms, immune cell activation, and oxidative stress, as well as traditional cardiovascular risk factors (eg, hypertension, diabetes, obesity) that promote cardiovascular diseases. In this overview, we summarize evidence from human and animal studies of the impacts of environmental exposures and climate change on cardiovascular health. In addition, we discuss strategies to reduce the impact of environmental risk factors on current and future cardiovascular disease burden, including urban planning, personal monitoring, and mitigation measures.

The prevalence of diabetes is estimated to reach almost 630 million cases worldwide by the year 2045; of current and projected cases, over 90% are type 2 diabetes. Air pollution exposure has been implicated in the onset and progression of diabetes. Increased exposure to fine particulate matter air pollution (PM2.5) is associated with increases in blood glucose and glycated hemoglobin (HbA1c) across the glycemic spectrum, including normoglycemia, prediabetes, and all forms of diabetes. Air pollution exposure is a driver of cardiovascular disease onset and exacerbation and can increase cardiovascular risk among those with diabetes. In this review, we summarize the literature describing the relationships between air pollution exposure, diabetes and cardiovascular disease, highlighting how airborne pollutants can disrupt glucose homeostasis. We discuss how air pollution and diabetes, via shared mechanisms leading to endothelial dysfunction, drive increased cardiovascular disease risk. We identify portable air cleaners as potentially useful tools to prevent adverse cardiovascular outcomes due to air pollution exposure across the diabetes spectrum, while emphasizing the need for further study in this particular population. Given the enormity of the health and financial impacts of air pollution exposure on patients with diabetes, a greater understanding of the interventions to reduce cardiovascular risk in this population is needed.

The prevalence of diabetes is estimated to reach almost 630 million cases worldwide by the year 2045; of current and projected cases, over 90% are type 2 diabetes. Air pollution exposure has been implicated in the onset and progression of diabetes. Increased exposure to fine particulate matter air pollution (PM_2.5) is associated with increases in blood glucose and glycated hemoglobin (HbA1c) across the glycemic spectrum, including normoglycemia, prediabetes, and all forms of diabetes. Air pollution exposure is a driver of cardiovascular disease onset and exacerbation and can increase cardiovascular risk among those with diabetes. In this review, we summarize the literature describing the relationships between air pollution exposure, diabetes and cardiovascular disease, highlighting how airborne pollutants can disrupt glucose homeostasis. We discuss how air pollution and diabetes, via shared mechanisms leading to endothelial dysfunction, drive increased cardiovascular disease risk. We identify portable air cleaners as potentially useful tools to prevent adverse cardiovascular outcomes due to air pollution exposure across the diabetes spectrum, while emphasizing the need for further study in this particular population. Given the enormity of the health and financial impacts of air pollution exposure on patients with diabetes, a greater understanding of the interventions to reduce cardiovascular risk in this population is needed.

Fine particulate matter air pollution (PM2.5) is a major contributor to cardiovascular morbidity and mortality, potentially via increased inflammation. PM2.5 exposure increases inflammatory biomarkers linked to cardiovascular disease, including CRP, IL-6 and TNFα. Portable air cleaners (PACs) reduce individual PM2.5 exposure but evidence is limited regarding whether PACs also reduce inflammatory biomarkers. We performed a systematic review and meta-analysis of trials evaluating the use of PACs to reduce PM2.5 exposure and inflammatory biomarker concentrations. We identified English-language articles of randomized sham-controlled trials evaluating high efficiency particulate air filters in non-smoking, residential settings measuring serum CRP, IL-6 and TNFα before and after active versus sham filtration, and performed meta-analysis on the extracted modeled percent change in biomarker concentration across studies. Of 487 articles identified, we analyzed 14 studies enrolling 778 participants that met inclusion criteria. These studies showed PACs reduced PM2.5 by 61.5 % on average. Of the 14 included studies, 10 reported CRP concentrations in 570 participants; these showed active PAC use was associated with 7 % lower CRP (95 % CI: −14 % to 0.0 %, p = 0.05). Nine studies of IL-6, with 379 participants, showed active PAC use was associated with 13 % lower IL-6 (95 % CI: [−23 %, −3 %], p = 0.009). Six studies, with 269 participants, reported TNF-α and demonstrated no statistical evidence of difference between active and sham PAC use. Portable air cleaners that reduce PM2.5 exposure can decrease concentrations of inflammatory biomarkers associated with cardiovascular disease. Additional studies are needed to evaluate clinical outcomes and other biomarkers.

INTRODUCTION/BACKGROUND:Perfluoroalkyl substances (PFAs) are ubiquitous, anthropogenic organic compounds that have been linked with cardiovascular disease and cardiovascular risk factors. Older, long-chain PFAs have been phased out due to adverse cardiometabolic health effect and replaced by newer short-chain PFAs. However, emerging research suggests that short-chain PFAs may also have adverse cardiovascular effects. Non-invasive measures of vascular function can detect preclinical cardiovascular disease and serve as a useful surrogate for early CVD risk. We hypothesized that serum concentrations of PFAs would be associated with noninvasive measures of vascular function, carotid-femoral pulse wave velocity (PWV) and brachial artery reactivity testing (BART), in adults with non-occupational exposure to PFAs. METHODS:We measured serum concentrations of 14 PFAs with hybrid solid-phase extraction and ultrahigh-performance liquid chromatography-tandem mass spectrometry in 94 adult outpatients with no known cardiovascular disease. We collected clinical and demographic data; and measured vascular function, PWV and BART, using standard protocols. We assessed associations of individual PFAs with log-transformed BART and PWV using linear regression. We used weighted quantile sum regression to assess effects of correlated PFA mixtures on BART and PWV. RESULTS:Ten PFAs were measured above the limit of detection in >50% of participants. Each standard deviation increase in concentration of perfluoroheptanoic acid (PFHpA) was associated with 15% decrease in BART (95% CI: -28.5, -0.17). The weighted index of a mixture of PFAs with correlated concentrations was inversely associated with BART: each tertile increase in the weighted PFA mixture was associated with 25% lower BART, with 73% of the effect driven by PFHpA. In contrast, no PFAs or mixtures were associated with PWV. CONCLUSIONS:Serum concentration of PFHpA, a new, short-chain PFA, was associated with impaired vascular function among outpatients without CVD. Our findings support a potential adverse cardiovascular effect of newer, short-chain PFAs.

BACKGROUND:Changes in subcutaneous adipose tissue (AT) structure and metabolism have been shown to correlate with the development of obesity and related metabolic disorders. Measurements of AT physiology could provide new insight into metabolic disease progression and response to therapy. An emerging functional imaging technology, diffuse optical spectroscopic imaging (DOSI), was used to obtain quantitative measures of near infrared (NIR) AT optical and physiological properties. METHODS:Ten overweight or obese adults were assessed during 3 months on calorie-restricted diets. DOSI-derived tissue concentrations of hemoglobin, water and lipid and the wavelength-dependent scattering amplitude (A) and slope (b) obtained from 30 abdominal locations and three time points (T0, T6, T12) were calculated and analyzed using linear mixed-effects models and were also used to form 3D surface images. RESULTS:Subjects lost a mean of 11.7±3.4% of starting weight, while significant changes in A (+0.23±0.04 mm(-1), adj. P<0.001),b (-0.17±0.04, adj. P<0.001), tissue water fraction (+7.2±1.1%, adj. P<0.001) and deoxyhemoglobin (1.1±0.3 μM, adj. P<0.001) were observed using mixed-effect model analysis. DISCUSSION:Optical scattering signals reveal alterations in tissue structure that possibly correlate with reductions in adipose cell volume, while water and hemoglobin dynamics suggest improved AT perfusion and oxygen extraction. These results suggest that DOSI measurements of NIR optical and physiological properties could be used to enhance understanding of the role of AT in metabolic disorders and provide new strategies for diagnostic monitoring of obesity and weight loss.

Gene expression changes are linked to air pollutant exposures in in vitro and animal experiments. However, limited data are available on how these outcomes relate to ambient air pollutant exposures in humans. We performed an exploratory analysis testing whether gene expression levels were associated with air pollution exposures in a Los Angeles area cohort of elderly subjects with coronary artery disease. Candidate genes (35) were selected from published studies of gene expression-pollutant associations. Expression levels were measured weekly in 43 subjects (≤ 12 weeks) using quantitative PCR. Exposures included gaseous pollutants O3, nitrogen oxides (NOx), and CO; particulate matter (PM) pollutants elemental and black carbon (EC, BC); and size-fractionated PM mass. We measured organic compounds from PM filter extracts, including polycyclic aromatic hydrocarbons (PAHs), and determined the in vitro oxidative potential of particle extracts. Associations between exposures and gene expression levels were analyzed using mixed-effects regression models. We found positive associations of traffic-related pollutants (EC, BC, primary organic carbon, PM 0.25-2.5 PAH and/or PM 0.25 PAH, and NOx) with NFE2L2, Nrf2-mediated genes (HMOX1, NQO1, and SOD2), CYP1B1, IL1B, and SELP. Findings suggest that NFE2L2 gene expression links associations of traffic-related air pollution with phase I and II enzyme genes at the promoter transcription level.

BACKGROUND:Mitochondria are the main source of reactive oxygen species (ROS). Human mitochondrial haplogroups are linked to differences in ROS production and oxidative-stress induced inflammation that may influence disease pathogenesis, including coronary artery disease (CAD). We previously showed that traffic-related air pollutants were associated with biomarkers of systemic inflammation in a cohort panel of subjects with CAD in the Los Angeles air basin. OBJECTIVE:We tested whether air pollutant exposure-associated inflammation was stronger in mitochondrial haplogroup H than U (high versus low ROS production) in this panel (38 subjects and 417 observations). METHODS:Inflammation biomarkers were measured weekly in each subject (≤ 12 weeks), including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein, interleukin-6 soluble receptor and tumor necrosis factor-soluble receptor II. We determined haplogroup by restriction fragment length polymorphism analysis. Air pollutants included nitrogen oxides (NOx), carbon monoxide (CO), organic carbon, elemental and black carbon (EC, BC); and particulate matter mass, three size fractions (<0.25 µm, 0.25-2.5 µm, and 2.5-10 µm in aerodynamic diameter). Particulate matter extracts were analyzed for organic compounds, including polycyclic aromatic hydrocarbons (PAH), and in vitro oxidative potential of aqueous extracts. Associations between exposures and biomarkers, stratified by haplogroup, were analyzed by mixed-effects models. RESULTS:IL-6 and TNF-α were associated with traffic-related air pollutants (BC, CO, NOx and PAH), and with mass and oxidative potential of quasi-ultrafine particles <0.25 µm. These associations were stronger for haplogroup H than haplogroup U. CONCLUSIONS:Results suggest that mitochondrial haplogroup U is a novel protective factor for air pollution-related systemic inflammation in this small group of subjects.