Predictors of healthy aging have not been well-studied using longitudinal data with demographic, clinical, subclinical, and genetic information. The objective was to identify predictors of poor ...health outcome at 10 years of follow-up in the Multi-Ethnic Study of Atherosclerosis (MESA).
Prospective cohort study.
Population-based sample from 6 U.S. communities.
4,355 participants In the MESA Study.
Poor health outcome at 10 years of follow-up was defined as having died or having clinical cardiovascular disease, depression, cognitive impairment, chronic obstructive pulmonary disease, or cancer other than non-melanoma skin cancer. Absolute risk regression was used to estimate risk differences in the outcome adjusting for demographic variables, clinical and behavioral risk factors, subclinical cardiovascular disease, and ApoE genotype. Models were weighted to account for selective attrition.
Mean age at 10 years of follow-up was 69.5 years; 1,480 participants had a poor health outcome, 2,157 participants were in good health, and 718 were unknown. Older age, smoking, not taking a statin, hypertension, diabetes, and higher coronary calcium score were associated with higher probability of poor health outcome. After multivariable adjustment, participants in the lowest income and educational categories had 7 to 14% greater absolute risk of poor health outcome at 10 years of follow-up compared to those in the next highest categories of income or education (P = 0.002 for both). Those in the lowest categories of both income and education had 21% greater absolute risk of poor health outcome compared to those in the highest categories of both income and education.
Low income and educational level predict poor health outcome at 10 years of follow-up in an aging cohort, independent of clinical and behavioral risk factors and subclinical cardiovascular disease.
The coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves ...classification of risk is unclear.
To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk.
CACS was measured by computed tomography in 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded from the primary analysis. Five-year risk estimates for incident CHD were categorized as 0% to less than 3%, 3% to less than 10%, and 10% or more using Cox proportional hazards models. Model 1 used age, sex, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement and compared the distribution of risk using model 2 vs model 1.
Incident CHD events.
During a median of 5.8 years of follow-up among a final cohort of 5878, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement = 0.25; 95% confidence interval, 0.16-0.34; P < .001). In model 1, 69% of the cohort was classified in the highest or lowest risk categories compared with 77% in model 2. An additional 23% of those who experienced events were reclassified as high risk, and an additional 13% without events were reclassified as low risk using model 2.
In this multi-ethnic cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.
BACKGROUND:Air pollution is associated with cardiovascular disease, and systemic inflammation may mediate this effect. We assessed associations between long- and short-term concentrations of air ...pollution and markers of inflammation, coagulation, and endothelial activation.
METHODS:We studied participants from the Multi-Ethnic Study of Atherosclerosis from 2000 to 2012 with repeat measures of serum C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, D-dimer, soluble E-selectin, and soluble Intercellular Adhesion Molecule-1. Annual average concentrations of ambient fine particulate matter (PM2.5), individual-level ambient PM2.5 (integrating indoor concentrations and time–location data), oxides of nitrogen (NOx), nitrogen dioxide (NO2), and black carbon were evaluated. Short-term concentrations of PM2.5 reflected the day of blood draw, day prior, and averages of prior 2-, 3-, 4-, and 5-day periods. Random-effects models were used for long-term exposures and fixed effects for short-term exposures. The sample size was between 9,000 and 10,000 observations for CRP, IL-6, fibrinogen, and D-dimer; approximately 2,100 for E-selectin; and 3,300 for soluble Intercellular Adhesion Molecule-1.
RESULTS:After controlling for confounders, 5 µg/m increase in long-term ambient PM2.5 was associated with 6% higher IL-6 (95% confidence interval = 2%, 9%), and 40 parts per billion increase in long-term NOx was associated with 7% (95% confidence interval = 2%, 13%) higher level of D-dimer. PM2.5 measured at day of blood draw was associated with CRP, fibrinogen, and E-selectin. There were no other positive associations between blood markers and short- or long-term air pollution.
CONCLUSIONS:These data are consistent with the hypothesis that long-term exposure to air pollution is related to some markers of inflammation and fibrinolysis.
This study evaluated the association of long- and short-term air pollutant exposures with flow-mediated dilation (FMD) and baseline arterial diameter (BAD) of the brachial artery using ultrasound in ...a large multicity cohort.
Exposures to ambient air pollution, especially long-term exposure to particulate matter <2.5 μm in aerodynamic diameter (PM(2.5)), are linked with cardiovascular mortality. Short-term exposure to PM(2.5) has been associated with decreased FMD and vasoconstriction, suggesting that adverse effects of PM(2.5) may involve endothelial dysfunction. However, long-term effects of PM(2.5) on endothelial dysfunction have not been investigated.
FMD and BAD were measured by brachial artery ultrasound at the initial examination of the Multi-Ethnic Study of Atherosclerosis. Long-term PM(2.5) concentrations were estimated for the year 2000 at each participant's residence (n = 3,040) using a spatio-temporal model informed by cohort-specific monitoring. Short-term PM(2.5) concentrations were based on daily central-site monitoring in each of the 6 cities.
An interquartile increase in long-term PM(2.5) concentration (3 μg/m(3)) was associated with a 0.3% decrease in FMD (95% confidence interval CI of difference: -0.6 to -0.03; p = 0.03), adjusting for demographic characteristics, traditional risk factors, sonographers, and 1/BAD. Women, nonsmokers, younger participants, and those with hypertension seemed to show a greater association of PM(2.5) with FMD. FMD was not significantly associated with short-term variation in PM(2.5) (-0.1% per 12 μg/m(3) daily increase 95% CI: -0.2 to 0.04 on the day before examination).
Long-term PM(2.5) exposure was significantly associated with decreased endothelial function according to brachial ultrasound results. These findings may elucidate an important pathway linking air pollution and cardiovascular mortality.
Atherosclerosis is a complex phenomenon manifesting several features typical of chronic inflammation and disorders of lipid metabolism. We assessed association of nuclear magnetic resonance (NMR) ...lipid variables and inflammatory markers with incident coronary artery calcium (CAC) and CAC progression among participants with baseline CAC ≥0.
MESA is a longitudinal cohort study of 6,814 participants (aged 45–85). 3,115 had CAC = 0 and 2,896 had CAC>0 at baseline. Repeat CAC measurements were obtained (mean duration of follow up, 6.5 years).
IL-6 (log pg/mL) and fibrinogen (50 mg/dL) were associated with a higher relative risk (RR) of incident CAC (HU) (RR = 1.09, p=0.010 & RR 1.05, p=0.004, respectively). Small LDL (100 nmol/L) (RR = 1.03, p<0.001) and log large VLDL (log nmol/L) (RR = 1.06, p=0.001) were associated with higher risks, whereas large HDL (μmol/L) was associated with an inverse risk of incident CAC (RR = 0.97, p< 0.001) in a model adjusted for follow up time, age, gender and race. Among participants with baseline CAC>0, progression of CAC was positively associated with hsCRP (log mg/L) (β = 1.99), IL-6 (log pg/mL) (β = 2.9), fibrinogen (50 mg/dL) (β = 1.0), large VLDL (log nmol/L) (β = 2.2), and small LDL (100 nmol/L) (β = 0.36) (all p values < 0.05) in a model adjusted for scanner type, age, gender and race. Relationships with inflammatory markers and NMR lipoprotein particles lost significance after adjustment for traditional risk factors and statin use. Traditional risk factors were strongly associated with both CAC incidence and progression with the exception of cholesterol parameters not associated with CAC progression in adjusted model.
Inflammatory markers and lipoprotein particles were associated with CAC incidence and progression in minimally adjusted models, but not after adjustment for traditional risk factors.
•Atherosclerosis is a complex phenomenon manifesting several features typical of chronic inflammation and disorders of lipid metabolism.•This study evaluates the association of inflammatory markers and specialized lipoprotein particles with incident coronary artery calcium (CAC) development and CAC progression over time.•Inflammatory markers and specialized lipoprotein particles were associated with CAC incidence and progression in minimally adjusted models, but not after adjustment for traditional risk factors.•Traditional risk factors were strongly associated with both CAC incidence and progression with the exception of cholesterol parameters not associated with CAC progression in adjusted model.
In type 2 diabetes mellitus (T2DM), it remains unclear whether coronary artery calcium (CAC) provides additional information about cardiovascular disease (CVD) mortality beyond the Framingham Risk ...Score (FRS) factors.
A total of 1,123 T2DM participants, ages 34-86 years, in the Diabetes Heart Study followed up for an average of 7.4 years were separated using baseline computed tomography scans of CAC (0-9, 10-99, 100-299, 300-999, and ≥1,000). Logistic regression was performed to examine the association between CAC and CVD mortality adjusting for FRS. Areas under the curve (AUC) with and without CAC were compared. Net reclassification improvement (NRI) compared FRS (model 1) versus FRS+CAC (model 2) using 7.4-year CVD mortality risk categories 0% to <7%, 7% to <20%, and ≥20%.
Overall, 8% of participants died of cardiovascular causes during follow-up. In multivariate analysis, the odds ratios (95% CI) for CVD mortality using CAC 0-9 as the reference group were, CAC 10-99: 2.93 (0.74-19.55); CAC 100-299: 3.17 (0.70-22.22); CAC 300-999: 4.41(1.15-29.00); and CAC ≥1,000: 11.23 (3.24-71.00). AUC (95% CI) without CAC was 0.70 (0.67-0.73), AUC with CAC was 0.75 (0.72-0.78), and NRI was 0.13 (0.07-0.19).
In T2DM, CAC predicts CVD mortality and meaningfully reclassifies participants, suggesting clinical utility as a risk stratification tool in a population already at increased CVD risk.
We aimed to assess the relationship of HDL (high-density lipoprotein)-mediated cholesterol mass efflux capacity (CMEC) with risk of incident peripheral artery disease (PAD).
CMEC was measured in 1458 ...Multi-Ethnic Study of Atherosclerosis participants between 2000 and 2002 as part of a case-control study matched for incident cardiovascular disease and progression of carotid plaque by ultrasound. Incident clinical PAD, adjudicated on the basis of a positive history for the presence of disease-related symptoms or treatment, was ascertained through 2015 in 1419 individuals without clinical PAD at baseline. Subclinical PAD, defined as an ankle-brachial index (ABI) ≤1.0, was assessed among 1255 individuals with a baseline ABI >1.0 and at least one follow-up ABI measurement 3–10 years later. Cox proportional hazards and relative risk regression modeling per SD increment of CMEC were used to determine the association of CMEC with clinical and subclinical PAD, respectively.
There were 38 clinical PAD and 213 subclinical PAD events that occurred over a mean follow-up of 6.0 and 6.5 years respectively. After adjustment for age, gender, and race, higher CMEC levels were not associated with clinical PAD (hazard ratio 1.25; 95% CI 0.89, 1.75) or subclinical PAD (risk ratio 1.02; 95% CI, 0.94, 1.11).
These findings suggest that HDL-mediated cholesterol efflux is not significantly associated with incident clinical and subclinical PAD.
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•Cholesterol mass efflux capacity (CMEC) quantifies the net movement of cholesterol between cells and HDL.•We determined the association of CMEC with incident PAD in a multi-ethnic cohort.•After adjustment for age, gender, race, higher CMEC levels were not associated with development of PAD.•Our findings suggest that CMEC may differentially impact atherosclerotic development across various vascular beds.
In 2001, we followed up all patients from the 1991 Olmsted County Multiple Sclerosis (MS) prevalence cohort. We found that the longer the duration of MS and the lower the disability, the more likely ...a patient is to remain stable and not progress. This is particularly powerful for patients with benign MS with Expanded Disability Status Scale score of 2 or lower for 10 years or longer who have a greater than 90% chance of remaining stable. This is important because these patients represent 17% of the entire prevalence cohort. These data should assist in the shared therapeutic decision‐making process of whether to start immunomodulatory medications. Ann Neurol 2004;56:303–306
A loss-of-function mutation (Q141K, rs2231142) in the ATP-binding cassette, subfamily G, member 2 gene (ABCG2) has been shown to be associated with serum uric acid levels and gout in Asians, ...Europeans, and European and African Americans; however, less is known about these associations in other populations. Rs2231142 was genotyped in 22,734 European Americans, 9,720 African Americans, 3,849 Mexican Americans, and 3,550 American Indians in the Population Architecture using Genomics and Epidemiology (PAGE) Study (2008-2012). Rs2231142 was significantly associated with serum uric acid levels (P = 2.37 x 10^sup -67^, P = 3.98 x 10^sup -5^, P = 6.97 x 10^sup -9^, and P = 5.33 x 10^sup -4^ in European Americans, African Americans, Mexican Americans, and American Indians, respectively) and gout (P = 2.83 x 10^sup -10^, P = 0.01, and P = 0.01 in European Americans, African Americans, and Mexican Americans, respectively). Overall, the T allele was associated with a 0.24-mg/dL increase in serum uric acid level (P = 1.37 x 10^ -80^) and a 1.75-fold increase in the odds of gout (P = 1.09 x 10^sup -12^). The association between rs2231142 and serum uric acid was significantly stronger in men, postmenopausal women, and hormone therapy users compared with their counterparts. The association with gout was also significantly stronger in men than in women. These results highlight a possible role of sex hormones in the regulation of ABCG2 urate transporter and its potential implications for the prevention, diagnosis, and treatment of hyperuricemia and gout. PUBLICATION ABSTRACT
We compared virtual-reality guided versus fluoroscopy-guided transseptal puncture by novice and experienced operators in a cardiac phantom. Outcome measures included accuracy, time, transseptal path ...distance, and a survey of the operator experience.
A transseptal simulator was created using a Plexiglas case and a 3D-printed cardiac phantom with a replaceable fossa ovalis, a customized support, and an electromagnetic tracking system. A precisely registered virtual-reality rendering was constructed. To display the transseptal instruments in virtual reality, we attached electromagnetic sensors to standard transseptal instruments, including the needle, dilator, and sheath. Each subject completed 6 simulated transseptal punctures (3 fluoroscopy-guided and 3 virtual-reality guided). We measured the distance traversed by the transseptal needle, accuracy, and time for each simulated transseptal puncture. Operators were then surveyed regarding their experience.
A total of 8 subjects (6 faculty, 2 fellows) completed the trial. We found that virtual-reality guidance resulted in significantly more accurate puncture site selection and, subjectively, was more intuitive for the operator, particularly for novices. None of the participants experienced negative symptoms in virtual reality that required cessation of the procedure.
Virtual reality compared with fluoroscopic guidance for transseptal puncture shows considerable promise, particularly for novice trainees, where it could lessen the learning curve. Current barriers to widespread implementation are discussed.
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