A randomized crossover trial of HEPA air filtration to reduce cardiovascular risk for near highway residents: Methods and approach.

BACKGROUND: Near highway residents are exposed to elevated levels of traffic-related air pollution (TRAP), including ultrafine particles, which are associated with adverse health effects. The efficacy of using in-home air filtration units that reduce exposure and potentially yield health benefits has not been tested in a randomized controlled trial. METHODS: We will conduct a randomized double-blind crossover trial of portable air filtration units for 200 adults 30 years and older who live in near-highway homes in Somerville, MA, USA. We will recruit participants from 172 households. The intervention periods will be one month of true or sham filtration, followed by a one-month wash out period and then a month of the alternate intervention. The primary health outcome will be systolic blood pressure (BP); secondary outcome measures will include diastolic and central BP, C-Reactive Protein (CRP) and D-dimer. Reasons for success or failure of the intervention will be evaluated in a subset of homes using indoor/outdoor monitoring for particulate pollution, personal monitoring, size and composition of particulate pollution, tracking of time spent in the room with the filter, and interviews for qualitative feedback. RESULTS: This trial has begun recruitment and is expected to take 2-3 years to be completed. Recruitment has been particularly challenging because of additional precautions required by the COVID-19 pandemic. DISCUSSION: This study has the potential to shed light on the value of using portable air filtration in homes close to highways to reduce exposure to TRAP and whether doing so has benefits for cardiovascular health.

Urban environment as an independent predictor of insulin resistance in a South Asian population.

BACKGROUND: Developing countries, such as India, are experiencing rapid urbanization, which may have a major impact on the environment: including worsening air and water quality, noise and the problems of waste disposal. We used health data from an ongoing cohort study based in southern India to examine the relationship between the urban environment and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: We utilized three metrics of urbanization: distance from urban center; population density in the India Census; and satellite-based land cover. Restricted to participants without diabetes (N = 6350); we built logistic regression models adjusted for traditional risk factors to test the association between urban environment and HOMA-IR. RESULTS: In adjusted models, residing within 0-20 km of the urban center was associated with an odds ratio for HOMA-IR of 1.79 (95% CI 1.39, 2.29) for females and 2.30 (95% CI 1.64, 3.22) for males compared to residing in the furthest 61-80 km distance group. Similar statistically significant results were identified using the other metrics. CONCLUSIONS: We identified associations between urban environment and HOMA-IR in a cohort of adults. These associations were robust using various metrics of urbanization and adjustment for individual predictors. Our results are of public health concern due to the global movement of large numbers of people from rural to urban areas and the already large burden of diabetes.

Urbanization as a risk factor for aortic stiffness in a cohort in India.

Urbanization is associated with higher prevalence of cardiovascular disease worldwide. Aortic stiffness, as measured by carotid-femoral pulse wave velocity is a validated predictor of cardiovascular disease. Our objective was to determine the association between urbanization and carotid-femoral pulse wave velocity. The analysis included 6166 participants enrolled in an ongoing population-based study (mean age 42 years; 58% female) who live in an 80 × 80 km region of southern India. Multiple measures of urbanization were used and compared: 1) census designations, 2) satellite derived land cover (crops, grass, shrubs or trees as rural; built-up areas as urban), and 3) distance categories based on proximity to an urban center. The association between urbanization and carotid-femoral pulse wave velocity was tested in sex-stratified linear regression models. People residing in urban areas had significantly (p < 0.05) elevated mean carotid-femoral pulse wave velocity compared to non-urban populations after adjustment for other risk factors. There was also an inverse association between distance from the urban center and mean carotid-femoral pulse wave velocity: each 10 km increase in distance was associated with a decrease in mean carotid-femoral pulse wave velocity of 0.07 m/s (95% CI: -0.09, -0.06 m/s). The association was stronger among older participants, among smokers, and among those with other cardiovascular risk factors. Further research is needed to determine which components in the urban environment are associated with higher carotid-femoral pulse wave velocity.

Mexican American and South Asian population-based cohorts reveal high prevalence of type 2 diabetes and crucial differences in metabolic phenotypes.

OBJECTIVE: Prevalence of type 2 diabetes varies by region and ancestry. However, most guidelines for the prevention of diabetes mellitus (DM) are based on European or non-Hispanic white populations. Two ethnic minority populations-Mexican Americans (MAs) in Texas, USA, and South Indians (SIs) in Tamil Nadu, India-have an increasing prevalence of DM. We aimed to understand the metabolic correlates of DM in these populations to improve risk stratification and DM prevention. RESEARCH DESIGN AND METHODS: The Cameron County Hispanic Cohort (CCHC; n=3023) served as the MA sample, and the Population Study of Urban, Rural, and Semi-Urban Regions for the Detection of Endovascular Disease (PURSE; n=8080) served as the SI sample. Using design-based methods, we calculated the prevalence of DM and metabolic comorbidities in each cohort. We determined the association of DM with metabolic phenotypes to evaluate the relative contributions of obesity and metabolic health to the prevalence of DM. RESULTS: In the CCHC (overall DM prevalence 26.2%), good metabolic health was associated with lower prevalence of DM, across age groups, regardless of obesity. In PURSE (overall prevalence 27.6%), probability of DM was not strongly associated with metabolic phenotypes, although DM prevalence was high in older age groups irrespective of metabolic health. CONCLUSION: Our study provides robust, population-based data to estimate the prevalence of DM and its associations with metabolic health. Our results demonstrate differences in metabolic phenotypes in DM, which should inform DM prevention guidelines in non-European populations.

Associations between Greenness, Impervious Surface Area, and Nighttime Lights on Biomarkers of Vascular Aging in Chennai, India.

BACKGROUND: India is undergoing rapid urbanization with simultaneous increases in the prevalence of cardiovascular disease (CVD). As urban areas become home to an increasing share of the world's population, it is important to understand relationships between the built environment and progression towards CVD. OBJECTIVE: We assessed associations between multiple measures of the built environment and biomarkers of early vascular aging (EVA) in the Population Study of Urban, Rural and Semiurban Regions for the Detection of Endovascular Disease and Prevalence of Risk Factors and Holistic Intervention Study (PURSE-HIS) in Chennai, India. METHODS: We performed a cross-sectional analysis of 3,150 study participants. EVA biomarkers included systolic and diastolic blood pressure (SBP and DBP), central pulse pressure (cPP) and flow-mediated dilatation (FMD). Multiple approaches were used to assign residential exposure to factors of the built environment: Moderate Resolution Imaging Spectroradiometer (MODIS)-derived normalized difference vegetation index (NDVI), a measure of vegetation health and greenness; Landsat-derived impervious surface area (ISA); and Visible Infrared Imaging Radiometer Suite (VIIRS)-derived nighttime lights (NTL). Multivariable regression models were used to assess associations between each built environment measure and biomarkers of EVA, adjusting for age, body mass index (BMI), cooking fuel type, energy intake, sex, physical activity, smoking, socioeconomic status, and stress. RESULTS: Residing in areas with higher ISA or NTL, or lower greenness, was significantly associated with elevated SBP, DBP, and cPP, and with lower FMD, adjusting for age, BMI, sex, smoking status, and other CVD risk factors. An interquartile range decrease in greenness had the largest increase in SBP [4.3 mmHg (95% CI: 2.9, 5.6)], DBP [1.2 mmHg (95% CI: 0.4, 2.0)] and cPP [3.1 mmHg (95% CI: 2.0, 4.1)], and the largest decrease in FMD [-1.5% (95%CI: -2.2%, -0.9%]. CONCLUSION: Greenness, ISA, and NTL were associated with increased SBP, DBP, and cPP, and with reduced FMD, suggesting a possible additional EVA pathway for the relationship between urbanization and increased CVD prevalence in urban India. https://doi.org/10.1289/EHP541.

Association of Long-Term Near-Highway Exposure to Ultrafine Particles with Cardiovascular Diseases, Diabetes and Hypertension.

Ultrafine particle (UFP) concentrations are elevated near busy roadways, however, their effects on prevalence of cardiovascular diseases, diabetes, and hypertension are not well understood. To investigate these associations, data on demographics, diseases, medication use, and time of activities were collected by in-home surveys for 704 participants in three pairs of near-highway and urban background neighborhoods in and near Boston (MA, USA). Body mass index (BMI) was measured for a subset of 435 participants. Particle number concentration (PNC, a measure of UFP) was collected by mobile monitoring in each area. Intra-neighborhood spatial-temporal regression models (approximately 20 m resolution) were used to estimate hourly ambient PNC at the residences of participants. We used participant time activity information to adjust annual average residential PNC values and assign individualized time activity adjusted annual average PNC exposures (TAA-PNC). Using multivariate logistic regression models, we found an odds ratio (OR) of 1.35 (95% CI: 0.83, 2.22) of TAA-PNC with stroke and ischemic heart diseases (S/IHD), an OR of 1.14 (95% CI: 0.81, 1.62) with hypertension, and an OR of 0.71 (95% CI: 0.46, 1.10) for diabetes. A subset analysis controlling for BMI produced slightly stronger associations for S/IHD (OR = 1.61, 95% CI: 0.88, 2.92) and hypertension (OR = 1.28, 95% CI: 0.81, 2.02), and no association with diabetes (OR = 1.09, 95% CI = 0.61, 1.96). Further research is needed with larger sample sizes and longitudinal follow-up.

Sodium Intake, Blood Pressure, and Dietary Sources of Sodium in an Adult South Indian Population.

BACKGROUND: The association between prevalence of hypertension and its relationship with dietary sodium intake has never been published from large epidemiological studies in the South Indian population before. OBJECTIVES: To assess sodium intake and its association with blood pressure, and major dietary sources of sodium in an adult population in southeastern India. METHODS: This study included a representative population-based sample of 8080 individuals (57% women) >20 years of age. Individuals with previous history of hypertension and outliers for sodium intake were excluded, resulting in a sample size of 6876, with 4269 from semi-urban/urban and 2607 from rural areas. Baseline measurements included evaluation of systolic (SBP) and diastolic (DBP) blood pressures, anthropometric, sociodemographic, and psychosocial parameters. Based on 24-hour recall, we calculated total daily sodium intake and the percentage contributed by each food group to the total sodium intake. Participants were assigned based on quintiles of dietary sodium intake. Mixed-effects multivariable linear regression models assessed the association of SBP and DBP with sodium intake. FINDINGS: Men had higher mean sodium intake (4.1 ± 2 versus 3.2 ± 1.7 g/day; P < 0.01) with higher mean SBP and DBP (123/77 versus 117/74 mm Hg; P < 0.01), and higher prevalence of hypertension (22.2% versus 12.9%; P < 0.01) compared with women. Mean dietary sodium intake was significantly higher in the hypertensive men (4.2 ± 2 g/day) and women (3.2 ± 1.7 g/day) compared with normotensive men (4 ± 2 g/day), and women (3.2 ± 1.7 g/day; P < 0.05). Significant (P < 0.01) increases in SBP and DBP were evident in men, but not women with increasing quintile of sodium intake. After multivariable adjustments, sodium intake was independently associated with SBP, but not DBP, in both sexes. The predominant source of dietary sodium in both semi-urban/urban and rural populations was from homemade foods where salt is part of the traditional recipe. CONCLUSION: In a South Indian population, the dietary intake of sodium was higher than recommendations by major dietary guidelines and was an independent predictor of SBP.

Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system.

Phosphodiesterase-4 (PDE-4) inhibitors promote memory by blocking the degradation of cAMP. Existing evidence also shows that neuronal survival and plasticity are dependent on the phosphorylation of cAMP-response element-binding protein. In this regard, PDE-4 inhibitors have also been shown to reverse pharmacologically and genetically induced memory impairment in animal models. In the present study, the authors examined the effect of both rolipram and roflumilast (PDE-4 inhibitors) on the impairment of learning and memory observed in hypertensive rats. Deoxycorticosterone acetate (DOCA) salt hypertensive model was used to induce learning and memory deficits. The mRNA expression of different PDE-4 subtypes along with the protein levels of pCREB and BDNF in the hippocampus was quantified. Systolic blood pressure was significantly increased in DOCA salt hypertensive rats when compared to sham operated rats. This effect was reversed by clonidine, an α2 receptor agonist, while PDE-4 inhibitors did not. PDE-4 inhibitors significantly improved the time-induced memory deficits in object recognition task (ORT). In DOCA salt hypertensive rats, the gene expression of PDE-4B and PDE-4D was significantly increased. Furthermore, both pCREB and BDNF showed decreased levels of expression in hypertensive rats in comparison to sham operated rats. Repeated administration of PDE-4 inhibitors significantly decreased both PDE-4B and PDE-4D with an increase in the expression of pCREB and BDNF in hypersensitive rats. Also, rolipram, roflumilast and roflumilast N-oxide showed a linear increase in the plasma and brain concentrations after ORT. Our present findings suggested that PDE-4 inhibitors ameliorate hypertension-induced learning impairment via cAMP/CREB signaling that regulates BDNF expression downstream in the rat hippocampus.

Population Study of Urban, Rural, and Semiurban Regions for the Detection of Endovascular Disease and Prevalence of Risk Factors and Holistic Intervention Study: Rationale, Study Design, and Baseline Characteristics of PURSE-HIS.

We designed and implemented the PURSE-HIS (Population Study of Urban, Rural and Semiurban Regions for the Detection of Endovascular Disease and Prevalence of Risk Factors and Holistic Intervention Study) to understand the prevalence and progression of subclinical and overt endovascular disease (EVD) and its risk factors in urban, semiurban, and rural communities in South India. The study is also designed to generate clinical evidence for effective, affordable, and sustainable community-specific intervention strategies to control risks factors for EVD. As of June 2012, 8,080 (urban: 2,221; semiurban: 2,821; rural: 3,038) participants >20 years of age were recruited using 2-stage cluster sampling. Baseline measurements included standard cardiovascular disease risk factors, sociodemographic factors, lifestyle habits, psychosocial factors, and nutritional assessment. Fasting blood samples were assayed for putative biochemical risk factors and urine samples for microalbuminuria. All nondiabetic participants underwent oral glucose tolerance test with blood and urine samples collected every 30 min for 2 h. Additional baseline measurements included flow-mediated brachial artery endothelial vasodilation, assessment of carotid intimal medial wall thickness using ultrasonography, screening for peripheral vascular disease using ankle and brachial blood pressures, hemodynamic screening using a high-fidelity applanation tonometry to measure central blood pressure parameters, and aortic pulse wave velocity. To assess prevalence of coronary artery disease, all participants underwent surface electrocardiography and documentation of ventricular wall motion abnormality and function using echocardiography imaging. To detect subclinical lesions, all eligible participants completed an exercise treadmill test. Prospectively, the study will assess progression of subclinical and overt EVD, including risk factor-outcome relation differences across communities. The study will also evaluate community-specific EVD prevention using traditional Indian system of medicine versus recognized allopathic (mainstream) systems of medicine.

Evidence for the healthy immigrant effect in older Chinese immigrants: a cross-sectional study.

BACKGROUND: Previous work has found that first-generation immigrants to developed nations tend to have better health than individuals born in the host country. We examined the evidence for the healthy immigrant effect and convergence of health status between Chinese immigrants (n = 147) and U.S. born whites (n = 167) participating in the cross-sectional Community Assessment of Freeway Exposure and Health study and residing in the same neighborhoods. METHODS: We used bivariate and multivariate models to compare disease prevalence and clinical biomarkers. RESULTS: Despite an older average age and lower socioeconomic status, Chinese immigrants were less likely to have asthma (OR = 0.20, 95% CI = 0.09-0.48) or cardiovascular disease (OR = 0.44, 95% CI = 0.20-0.94), had lower body mass index (BMI), lower inflammation biomarker levels, lower average sex-adjusted low-density lipoprotein (LDL) cholesterol, and higher average sex-adjusted high-density lipoprotein (HDL) cholesterol. However, there was no significant difference in the prevalence of diabetes or hypertension. Duration of time in the U.S. was related to cardiovascular disease and asthma but was not associated with diabetes, hypertension, BMI, HDL cholesterol, LDL cholesterol, socioeconomic status, or health behaviors. CONCLUSIONS: The lower CVD and asthma prevalence among the Chinese immigrants may be partially attributed to healthier diets, more physical activity, lower BMI, and less exposure to cigarette smoke. First generation immigrant status may be protective even after about two decades.

Cardiac arrest in the organ donor does not negatively influence recipient survival after heart transplantation.

OBJECTIVE: Cardiac arrest in the organ donor raises concerns about the possibility of ischemic cardiac damage. We evaluated the outcome of heart transplantation in patients receiving an organ from donors who had suffered a period of cardiac arrest. METHODS: Demographics, operative details and outcome data were obtained retrospectively. Actuarial survival was reported using Kaplan-Meier analysis and compared with the log rank test. Cox proportional hazards regression was used to model risk adjusted survival. RESULTS: Between 1 January 1991 and 1 November 2004 38 patients were transplanted with hearts from multiorgan donors who were resuscitated after a cardiac arrest. The mean (standard deviation) duration of cardiac arrest was 15 (8)min. The interval between donor cardiac arrest and organ excision was 69 (5)h. The 30-day mortality was 2.6% (1/38). In the same interim 566 patients underwent cardiac transplantation with hearts from organ donors without a cardiac arrest. Median time to follow up was 61 months (IQR 15-166). One and 5-year survival comparing the arrest and non-arrest groups was 94.2% versus 83.6% and 79.8% versus 74.5%, respectively, p=0.35. Donor cardiac arrest was not an adverse predictor of mortality on multivariate analysis, the adjusted odds ratio was 0.86 (95% CI 0.60-1.25, p=0.42). CONCLUSIONS: With careful case selection, there was no evidence that survival after cardiac transplantation was worse following a period of cardiac arrest in the organ donor. A history of cardiac arrest in the organ donor should not exclude an organ from being considered for transplantation.

CTLA4-Ig-based conditioning regimen to induce tolerance to cardiac allografts.

BACKGROUND: Transplant rejection and toxicity associated with chronic immunosuppressive therapy remain a major problem. Mixed hematopoietic chimerism has been shown to produce tolerance to solid organ transplants. However, currently available protocols to induce mixed hematopoietic chimerism invariably require toxic pre-conditioning. In this study, we investigated a non-toxic CTLA4-Ig-based protocol to induce donor-specific tolerance to cardiac allografts in rats. METHODS: Fully mismatched, 4 to 6 week old ACI (RT1.A(a)) and Wistar Furth (RT1.A(u)) rats were used as cell/organ donors and recipients, respectively. Recipients were treated with CTLA4-Ig 2 mg/kg/day (on days 0, 2, 4, 6, 8), tacrolimus 1 mg/kg/day (daily, from days 0 to 9), and a single dose of anti-lymphocyte serum (10 mg) on day 10, soon after total body irradiation (300 cGy) and donor bone marrow (100 x 10(6) T-cell depleted cells) transplantation (BMT). Six weeks after BMT, chimeric animals received heterotopic heart transplants. RESULTS: Hematopoietic chimerism was 18.8 +/- 10.6% at day 30, and was stable (24 +/- 10%) at 1 year post-BMT; there was no graft versus host disease. Chimeric recipients (RT1.A(u)) permanently accepted (>360 days) donor-specific (RT1.A(a); n = 6) hearts, yet rapidly rejected (<9 days) third-party hearts (RT1.A(l); n = 5). Graft (heart) tolerant (>100 days) recipients accepted donor-specific secondary skin grafts (>200 days) while rejected the third-party skin grafts (<9 days). Lymphocytes of graft tolerant animals demonstrated hyporesponsiveness in mixed lymphocyte cultures in a donor-specific manner. Tolerant graft histology showed no obliterative arteriopathy or chronic rejection. CONCLUSIONS: The CTLA4-Ig based conditioning regimen with donor BMT produced mixed chimerism and induced donor- specific tolerance to cardiac allografts.

The history and development of direct coronary surgery without cardiopulmonary bypass.

The history of direct myocardial revascularization without cardiopulmonary bypass dates to 1961 in the dawn of coronary artery surgery. With the introduction and development of techniques of extracorporeal circulation around the same time, beating heart surgery was largely abandoned. Over the subsequent decades, cardiopulmonary bypass and electromechanical cardioplegic arrest became popular as means of revascularization in a bloodless and motionless field. While coronary artery surgery on the arrested heart remained undisputed for decades, myocardial revascularization on the beating heart was pursued by a few pioneering surgeons around the world, based on the belief that coronary revascularization could be performed equally well without the detrimental effects of cardiopulmonary bypass and electromechanical arrest. Various concepts and techniques developed during the 1980s by these pioneers enabled minimally invasive coronary surgery to be performed in the early 1990s. This break from the mainstream allowed selective myocardial revascularization using a minimal incision and no cardiopulmonary bypass to develop and constructed a base for future extensive revascularizations off-pump. With the subsequent explosion of new techniques for coronary exposure and myocardial stabilization, complete revascularization without cardiopulmonary bypass became possible with consistent results. Emerging from the preview of only a few surgeons just a decade ago, off-pump surgery is currently one of the accepted modalities for complete myocardial revascularization worldwide. This paradigm shift in the approach to myocardial revascularization has led to exiting new future possibilities, such as beating heart totally endoscopic coronary artery surgery.