Markers of Inflammation and Coagulation after Long-Term Exposure to Coarse Particulate Matter: A Cross-Sectional Analysis from the Multi-Ethnic Study of Atherosclerosis

Background

Toxicological research suggests that coarse particles (PM_10–2.5) are inflammatory, but responses are complex and may be best summarized by multiple inflammatory markers. Few human studies have investigated associations with PM_10–2.5 and, of those, none have explored long-term exposures. Here we examine long-term associations with inflammation and coagulation in the Multi-Ethnic Study of Atherosclerosis.

Methods

Participants included 3,295 adults (45–84 years of age) from three metropolitan areas. Site-specific spatial models were used to estimate 5-year concentrations of PM_10–2.5 mass and copper, zinc, phosphorus, silicon, and endotoxin found in PM_10–2.5. Outcomes included interleukin-6, C-reactive protein, fibrinogen, total homocysteine, D-dimer, factor VIII, plasmin–antiplasmin complex, and inflammation and coagulation scores. We used multivariable regression with multiply imputed data to estimate associations while controlling for potential confounders, including co-pollutants such as fine particulate matter.

Results

Some limited evidence was found of relationships between inflammation and coagulation and PM_10–2.5. Endotoxin was the PM_10–2.5 component most strongly associated with inflammation, with an interquartile range (IQR) increase (0.08 EU/m³) associated with 0.15 (95% CI: 0.01, 0.28; p = 0.03) and 0.08 (95% CI: –0.07, 0.23; p = 0.28) higher inflammation scores before and after control for city, respectively. Copper was the component with the strongest association with coagulation, with a 4-ng/m³ increase associated with 0.19 (95% CI: 0.08, 0.30; p = 0.0008) and 0.12 (95% CI: –0.05, 0.30; p = 0.16) unit higher coagulation scores before and after city adjustment, respectively.

Conclusions

Our cross-sectional analysis provided some evidence that long-term PM_10–2.5 exposure was associated with inflammation and coagulation, but associations were modest and depended on particle composition.

Citation

Adar SD, D’Souza J, Mendelsohn-Victor K, Jacobs DR Jr, Cushman M, Sheppard L, Thorne PS, Burke GL, Daviglus ML, Szpiro AA, Diez Roux AV, Kaufman JD, Larson TV. 2015. Markers of inflammation and coagulation after long-term exposure to coarse particulate matter: a cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis. Environ Health Perspect 123:541–548; http://dx.doi.org/10.1289/ehp.1308069     

Potassium intake and risk of incident type 2 diabetes mellitus: the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Aims/hypothesis  

Serum potassium has been found to be a significant predictor of diabetes risk, but the effect of dietary potassium on diabetes risk is not clear. We sought to determine if dietary potassium is associated with risk of incident type 2 diabetes in young adults.     

Response rates to a questionnaire 26 years after baseline examination with minimal interim participant contact and baseline differences between respondents and nonrespondents

Research on response rates to surveys mailed to study participants decades after baseline examination, with minimal interim contact, is limited. This paper documents response rates to a 26-year follow-up survey of surviving participants from a large cohort in Illinois and compares baseline characteristics of nonrespondents and respondents. Mortality follow-up of the Chicago Heart Association Detection Project in Industry 1967-1973 cohort involved minimal or no participant contact since baseline. In 1996, a 26-year follow-up questionnaire was mailed to all surviving participants aged 65 years or older. Current addresses were obtained from the Health Care Financing Administration for 96.5 percent of 12,409 participants in our analyses. Total response rates were 59.8 percent and, for participants for whom Health Care Financing Administration addresses were available, 60.8 percent. A higher response rate was obtained for younger recipients, men, Whites, more-educated persons, nonsmokers, and those with a better cardiovascular risk profile at baseline. A graded negative relation was found between number of cardiovascular risk factors at baseline and response rates obtained in 1996. Use of Health Care Financing Administration records as an additional follow-up method and factors that influence response rates are discussed. In conclusion, long-term follow-up of older surviving participants is feasible if current addresses can be obtained from standardized sources.     

Comparison of low risk and higher risk profiles in middle age to frequency and quantity of coronary artery calcium years later

Little is known about the relation of having favorable levels of all major cardiovascular risk factors (low risk [LR]) earlier in life to coronary artery calcium (CAC) later in life. From 2002 to 2003, CAC was compared in participants aged >60 years who were LR (n = 42) with those not LR (n = 39) at baseline (from 1967 to 1973). Despite adverse changes in risk factors, the prevalence of measurable CAC and mean CAC scores were less for LR participants than for non-LR participants (60% vs 77%, p = 0.09, and 217 vs 443, p = 0.05, respectively).     

Low risk-factor profile and long-term cardiovascular and noncardiovascular mortality and life expectancy: findings for 5 large cohorts of young adult and middle-aged men and women

CONTEXT: Three major coronary risk factors-serum cholesterol level, blood pressure, and smoking-increase incidence of coronary heart disease (CHD) and related end points. In previous investigations, risks for low-risk reference groups were estimated statistically because samples contained too few such people to measure risk. OBJECTIVE: To measure long-term mortality rates for individuals with favorable levels for all 3 major risk factors, compared with others. DESIGN: Two prospective studies, involving 5 cohorts based on age and sex, that enrolled persons with a range of risk factors. Low risk was defined as serum cholesterol level less than 5.17 mmol/L (<200 mg/dL), blood pressure less than orequal to 120/80 mm Hg, and no current cigarette smoking. All persons with a history of diabetes, myocardial infarction (MI), or, in 3 of 5 cohorts, electrocardiogram (ECG) abnormalities, were excluded. SETTING AND PARTICIPANTS: In 18 US cities, a total of 72144 men aged 35 through 39 years and 270671 men aged 40 through 57 years screened (1973-1975) for the Multiple Risk Factor Intervention Trial (MRFIT); in Chicago, a total of 10025 men aged 18 through 39 years, 7490 men aged 40 through 59 years, and 6229 women aged 40 through 59 years screened (1967-1973) for the Chicago Heart Association Detection Project in Industry (CHA) (N = 366559). MAIN OUTCOME MEASURES: Cause-specific mortality during 16 (MRFIT) and 22 (CHA) years, relative risks (RRs) of death, and estimated greater life expectancy, comparing low-risk subcohorts vs others by age strata. RESULTS: Low-risk persons comprised only 4.8% to 9.9% of the cohorts. All 5 low-risk groups experienced significantly and markedly lower CHD and cardiovascular disease death rates than those who had elevated cholesterol level, or blood pressure, or smoked. For example, age-adjusted RRs of CHD mortality ranged from 0.08 for CHA men aged 18 to 39 years to 0.23 for CHA men aged 40 through 59 years. The age-adjusted relative risks (RRs) for all cardiovascular disease mortality ranged from 0.15 for MRFIT men aged 35 through 39 years to 0.28 for CHA men aged 40 through 59 years. The age-adjusted RR for all-cause mortality rate ranged from 0.42 for CHA men aged 40 through 59 years to 0.60 for CHA women aged 40 through 59 years. Estimated greater life expectancy for low-risk groups ranged from 5.8 years for CHA women aged 40 through 59 years to 9.5 years for CHA men aged 18 through 39 years. CONCLUSIONS: Based on these very large cohort studies, for individuals with favorable levels of cholesterol and blood pressure who do not smoke and do not have diabetes, MI, or ECG abnormalities, long-term mortality is much lower and longevity is much greater. A substantial increase in the proportion of the population at lifetime low risk could contribute decisively to ending the CHD epidemic.     

Food omega-3 fatty acid intake of individuals (total, linolenic acid, long-chain) and their blood pressure: INTERMAP study

Findings from short-term randomized trials indicate that dietary supplements of omega-3 polyunsaturated fatty acids (PFA) lower blood pressure of hypertensive persons, but effect size in nonhypertensive individuals is small and nonsignificant. Data are lacking on food omega-3 PFA and blood pressure in general populations. The International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP) is an international cross-sectional epidemiologic study of 4680 men and women ages 40 to 59 from 17 population-based samples in China, Japan, United Kingdom, and United States. We report associations of food omega-3 PFA intake (total, linolenic acid, long-chain) of individuals with blood pressure. Systolic and diastolic blood pressure were measured 8 times at 4 visits. With several models to control for possible confounders (dietary, other), linear regression analyses showed inverse relationship of total omega-3 PFA from food (percent kilocalories, from four 24-hour dietary recalls) to systolic and diastolic blood pressures. With adjustment for 17 variables, estimated systolic blood pressure/diastolic blood pressure differences with 2 standard deviation higher (0.67% kcal) omega-3 PFA were -0.55/-0.57 mm Hg (Z-score -1.33, -2.00); for 2238 persons without medical or dietary intervention, -1.01/-0.98 mm Hg (Z -1.63, -2.25); for 2038 nonhypertensive persons from this sub-cohort, -0.91/-0.92 mm Hg (Z -1.80, -2.38). For linolenic acid (largely from vegetable foods), blood pressure differences were similar, eg, for the 2238 "nonintervened" individuals, -0.97/-0.87 mm Hg (Z -1.52, -1.95); blood pressure differences were -0.32/-0.45 mm Hg for long-chain omega-3 PFA (largely from fish). In summary, food omega-3 PFA intake related inversely to blood pressure, including in nonhypertensive persons, with small estimated effect size. Food omega-3 PFA may contribute to prevention and control of adverse blood pressure levels.     

Longitudinal association between toenail selenium levels and measures of subclinical atherosclerosis: The CARDIA trace element study

Objectives

To examine the longitudinal association between toenail selenium levels and subclinical atherosclerosis over an 18-year period.

Methods

Toenail selenium concentrations were examined among 3112 Americans age 20–32 years in 1987 and measured by instrumental neutron-activation analysis. Subclinical atherosclerosis, including common, bulb and internal carotid intima–media thickness (CIMT), was measured in 2005 and coronary artery calcium (CAC) score in 2000 and 2005. General linear regression was developed examining the relation between toenail selenium levels and CIMTs, and logistic regression for repeated outcomes was employed estimating the risk of having CAC > 0.

Results

After adjustment for potential confounders, no associations were observed between toenail selenium levels and CIMTs as well as CAC score. Comparing participants in the highest with the lowest quintile of selenium, the CIMT was 0.005 mm (SE = 0.008 mm, P_trend = 0.39), 0.018 mm (SE = 0.019 mm, P_trend = 0.49), and 0.017 mm (SE = 0.014 mm, P_trend = 0.21) thicker measured in common, bulb and internal carotid, respectively. The adjusted odds ratio of having CAC > 0 was 0.95 (95% CI: 0.67–1.35; P_trend = 0.999).

Conclusions

No associations were observed between toenail selenium and measures of subclinical atherosclerosis among American young adults. This study does not support an atherosclerotic mechanism of selenium for risk reduction of cardiovascular disease.