Influenza vaccination and use of lipid lowering therapies in adults with atherosclerotic cardiovascular disease: An analysis of the Behavioral Risk Factor Surveillance System (BRFSS).

BACKGROUND: Influenza vaccination and lipid lowering therapy (LLT) are evidence-based interventions with substantial benefit for individuals with established atherosclerotic cardiovascular disease (ASCVD). However, levels of influenza immunization and LLT use are low, possibly due to pervasive fear-based misinformation uniquely targeting vaccines and LLT. Whether being unvaccinated for influenza predicts lower utilization of LLT is unknown. OBJECTIVES: We tested the hypothesis that American adults with ASCVD who are unvaccinated for influenza have lower use of LLT even after accounting for traditional factors associated with underuse of preventive therapies. METHODS: We pooled 2017, 2019, and 2021 survey data from the Behavioral Risk Factor Surveillance System (BRFSS), and selected respondents aged 40 to 75 years with self-reported ASCVD. We used logistic regression models adjusted for potential confounders to examine the association between influenza vaccination and self-reported LLT use. We performed a sensitivity analysis with multiple imputation to account for missing data. All analyses accounted for complex survey weighting. RESULTS: Of 66,923 participants with ASCVD, 55% reported influenza vaccination in the last year and 76% reported using LLT. Being unvaccinated for influenza was associated with lower odds of LLT use (OR 0.54; 95% CI 0.50, 0.58; P< .001). In a multivariable regression model adjusting for demographics and comorbidities, this association remained statistically significant (aOR 0.58, 95% CI 0.52, 0.64, P < .001). After additional adjustment for preventive care engagement, health care access, and use patterns of other cardiovascular medications this association persisted (aOR 0.66; 95% CI 0.60, 0.74; P < .001). There were no significant differences across subgroups, including those with and without hyperlipidemia. CONCLUSIONS: Unvaccinated status for influenza was independently associated with 34% lower odds of LLT use among American adults with ASCVD after adjustment for traditional factors linked to underuse of preventive therapies. This finding identifies a population with excess modifiable ASCVD risk, and supports investigation into nontraditional mechanisms driving underuse of preventive therapies, including fear-based misinformation.

Short-term air pollution levels and sickle cell disease hospital encounters in South Carolina: A case-crossover analysis.

BACKGROUND: Sickle cell disease (SCD) is a genetic disorder and symptoms may be sensitive to environmental stressors. Although it has been hypothesized that exposure to outdoor air pollution could trigger acute SCD events, evidence is limited. METHODS: We obtained SCD administrative data on hospital encounters in South Carolina from 2002 to 2019. We estimated outdoor air pollutant (particulate matter<2.5 µm (PM2.5), ozone (O3), and PM2.5 elemental carbon (EC) concentrations at residential zip codes using spatio-temporal models. Using a random bi-directional, fixed-interval case-crossover study design, we investigated the relationship between air pollution exposure over 1-, 3-, 5-, 9-, and14-day periods with SCD hospital encounters. RESULTS: We studied 8410 patients with 144,129 hospital encounters. We did not observe associations among all patients with SCD and adults for PM2.5, O3, and EC. We observed positive associations among children for 9- and 14-day EC (OR: 1.05 (95% confidence interval (CI): 1.02, 1.08) and OR: 1.05 (95% CI: 1.02, 1.09), respectively) and 9- and 14-day O3 (OR: 1.04 (95%CI: 1.00, 1.08)) for both. CONCLUSIONS: Our findings suggest that short-term (within two-weeks) levels of EC and O3 and may be associated with SCD hospital encounters among children. Two-pollutant model results suggest that EC is more likely responsible for effects on SCD than O3. More research is needed to confirm our findings.

Sociopolitical stress and acute cardiovascular disease hospitalizations around the 2016 presidential election.

Previous research suggests that stressors may trigger the onset of acute cardiovascular disease (CVD) events within hours to days, but there has been limited research around sociopolitical events such as presidential elections. Among adults ≥18 y of age in Kaiser Permanente Southern California, hospitalization rates for acute CVD were compared in the time period immediately prior to and following the 2016 presidential election date. Hospitalization for CVD was defined as an inpatient or emergency department discharge diagnosis of acute myocardial infarction (AMI) or stroke using International Classification of Diseases, 10th revision codes. Rate ratios (RR) and 95% confidence intervals (CIs) were calculated comparing CVD rates in the 2 d following the 2016 election to rates in the same 2 d of the prior week. In a secondary analysis, AMI and stroke were analyzed separately. The rate of CVD events in the 2 d after the 2016 presidential election (573.14 per 100,000 person-years [PY]) compared to the rate in the window prior to the 2016 election (353.75 per 100,000 PY) was 1.62 times higher (95% CI 1.17, 2.25). Results were similar across sex, age, and race/ethnicity groups. The RRs were similar for AMI (RR 1.67, 95% CI 1.00, 2.76) and stroke (RR 1.59, 95% CI 1.03, 2.44) separately. Transiently heightened cardiovascular risk around the 2016 election may be attributable to sociopolitical stress. Further research is needed to understand the intersection between major sociopolitical events, perceived stress, and acute CVD events.

Post-transplant mortality and graft failure after induction immunosuppression among Black heart transplant recipients in the United States.

Black heart transplant recipients are more likely to receive induction immunosuppression compared to other races because of higher rates of acute rejection, graft failure, and mortality. However, it is not known whether contemporary induction immunosuppression improves their post-transplant outcomes. To evaluate whether Black patients who were prescribed induction immunosuppression therapy have lower all-cause mortality or graft-failure rates compared to those who were not, we studied Black U.S. adult heart transplant recipients in the Scientific Registry of Transplant Recipients database (2008-2018). We used multivariable Cox proportional hazards regression analysis to compare the hazards of all-cause mortality or graft failure as a composite, for patients who were prescribed induction immunosuppression and those who were not. Among 5160 recipients, 2787 (54.0%) were prescribed induction immunosuppression and 2373 (46.0%) were not. There was no evidence of survival differences according to induction immunosuppression for the composite of all-cause mortality or graft failure (aHR = 1.13, 95% CI 0.96-1.32), mortality (aHR = 1.14, 95% CI 0.97-1.34), graft failure (aHR = 1.05, 95% CI 0.82-1.34) and acute rejection (aHR = 1.00, 95% CI 0.89-1.12). Given the side effects of treatment, future guidelines should reconsider the recommendation for induction immunosuppression among Black patients.

Exposure to Air Pollution and Particle Radioactivity With the Risk of Ventricular Arrhythmias.

BACKGROUND: Individuals are exposed to air pollution and ionizing radiation from natural sources through inhalation of particles. This study investigates the association between cardiac arrhythmias and short-term exposures to fine particulate matter (particulate matter ≤2.5 µm aerodynamic diameter; PM2.5) and particle radioactivity. METHODS: Ventricular arrhythmic events were identified among 176 patients with dual-chamber implanted cardioverter-defibrillators in Boston, Massachusetts between September 2006 and June 2010. Patients were assigned exposures based on residential addresses. Daily PM2.5 levels were estimated at 1-km×1-km grid cells from a previously validated prediction model. Particle gross ß activity was used as a surrogate for particle radioactivity and was measured from several monitoring sites by the US Environmental Protection Agency's monitoring network. The association of the onset of ventricular arrhythmias (VA) with 0- to 21-day moving averages of PM2.5 and particle radioactivity (2 single-pollutant models and a 2-pollutant model) before the event was examined using time-stratified case-crossover analyses, adjusted for dew point and air temperatures. RESULTS: A total of 1,050 VA were recorded among 91 patients, including 123 sustained VA among 25 of these patients. In the single-pollutant model of PM2.5, each interquartile range increase in daily PM2.5 levels for a 21-day moving average was associated with 39% higher odds of a VA event (95% CI, 12%-72%). In the single-pollutant model of particle radioactivity, each interquartile range increase in particle radioactivity for a 2-day moving average was associated with 13% higher odds of a VA event (95% CI, 1%-26%). In the 2-pollutant model, for the same averaging window of 21 days, each interquartile range increase in daily PM2.5 was associated with an 48% higher odds of a VA event (95% CI, 15%-90%), and each interquartile range increase of particle radioactivity with a 10% lower odds of a VA event (95% CI, -29% to 14%). We found that with higher levels of particle radioactivity, the effect of PM2.5 on VAs is reduced. CONCLUSIONS: In this high-risk population, intermediate (21-day) PM2.5 exposure was associated with higher odds of a VA event onset among patients with known cardiac disease and indication for implanted cardioverter-defibrillator implantation independently of particle radioactivity.

Air Pollution and Risk of Placental Abruption: A Study of Births in New York City, 2008-2014.

We evaluated the associations of exposure to fine particulate matter (particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) at concentrations of <12 µg/m3, 12-14 µg/m3, and ≥15 µg/m3) and nitrogen dioxide (at concentrations of <26 parts per billion (ppb), 26-29 ppb, and ≥30 ppb) with placental abruption in a prospective cohort study of 685,908 pregnancies in New York, New York (2008-2014). In copollutant analyses, these associations were examined using distributed-lag nonlinear models based on Cox models. The prevalence of abruption was 0.9% (n = 6,025). Compared with a PM2.5 concentration less than 12 µg/m3, women exposed to PM2.5 levels of ≥15 µg/m3 in the third trimester had a higher rate of abruption (hazard ratio (HR) = 1.68, 95% confidence interval (CI): 1.41, 2.00). Compared with a nitrogen dioxide concentration less than 26 ppb, women exposed to nitrogen dioxide levels of 26-29 ppb (HR = 1.11, 95% CI: 1.02, 1.20) and ≥30 ppb (HR = 1.06, 95% CI: 0.96, 1.24) in the first trimester had higher rates of abruption. Compared with both PM2.5 and nitrogen dioxide levels less than the 95th percentile in the third trimester, rates of abruption were increased with both PM2.5 and nitrogen dioxide ≥95th percentile (HR = 1.44, 95% CI: 1.15, 1.80) and PM2.5 ≥95th percentile and nitrogen dioxide <95th percentile (HR = 1.43 95% CI: 1.23, 1.66). Increased levels of PM2.5 exposure in the third trimester and nitrogen dioxide exposure in the first trimester are associated with elevated rates of placental abruption, suggesting that these exposures may be important triggers of premature placental separation through different pathways.

Cannabis use disorder and perioperative outcomes in vascular surgery.

BACKGROUND: Heavy cannabis use is known to have an adverse impact on cardiovascular and cerebrovascular outcomes in the general population and in patients presenting for surgery. However, there have been no studies that have focused on patients undergoing vascular surgical procedures. The objective of this study was to determine the perioperative risk of cannabis use disorder (CUD), primarily cardiovascular risk, in perioperative vascular surgery patients. METHODS: Using the National Inpatient Sample from 2006 to 2015, we conducted a retrospective cohort study involving those undergoing one of six elective and emergent vascular surgical procedures (carotid endarterectomy [CEA], infrainguinal bypasses, open abdominal aortic aneurysm repair, aortobifemoral bypass, endovascular aortic aneurysm repair, or peripheral arterial endovascular procedures). Patients with CUD identified by the International Classification of Diseases, 9th edition, were matched with patients without CUD in a 1:1 ratio using propensity scores. The primary outcome was perioperative myocardial infarction (MI). Secondary outcomes include stroke, sepsis, deep vein thrombosis, pulmonary embolus, acute kidney injury requiring dialysis, respiratory failure, in-hospital mortality, total cost, and length of stay. RESULTS: We identified a total cohort of 510,007 patients. Over the study period, the recorded prevalence of CUD increased from 1.3/1000 to 10.3/1000 admissions (P < .001). After propensity score matching the cohort consisted of 4684 patients. Those with CUD had a higher incidence of perioperative MI (3.3% vs 2.1%; odds ratio [OR], 1.56; 95% confidence interval [CI], 1.09-2.24; P = .016) and perioperative stroke (5.5% vs 3.5%; OR, 1.59; 95% CI, 1.20-2.12; P = .0013) than patients without CUD. In a sensitivity analysis, where the risk was evaluated separately by type of procedure, the higher incidence of perioperative stroke was primarily seen among those undergoing CEA. Patients with CUD had a lower incidence of sepsis (3.3% vs 5.1%; OR, 0.64; 95% CI, 0.47-0.85; P = .0024). We obtained similar results in a sensitivity analysis that included all patients in the complete unmatched cohort and adjusted for confounding using logistic regression models accounting for the survey design, although the findings of sepsis and stroke failed to reach statistical significance after correcting for multiple testing (MI P = .001; stroke P = .031; sepsis P = .009). CONCLUSIONS: CUD was associated with a significantly higher incidence of perioperative MI in vascular surgery patients. Those with CUD had a greater incidence of diagnosis of acute perioperative stroke when undergoing CEA. Owing to limitations in administrative data, it is unclear if this represents a true effect or selection bias. These findings warrant further investigation in a prospective cohort.

Baseline sleep quality, stress, and depressive symptoms, and subsequent headache occurrence in a six-week prospective cohort study of patients with episodic migraine.

OBJECTIVES/BACKGROUND: Despite the high prevalence of sleep disturbance, stress, and depressive symptoms among patients with episodic migraine, there has been limited prospective research examining how these comorbid symptoms relate to future headache risk. METHODS: We conducted an a priori secondary analysis of a prospective cohort study of 98 adults with episodic migraine recruited through Harvard-affiliated medical centers and local college student clinics in Boston, MA. At baseline, participants completed validated questionnaires on sleep quality, stress, and depressive symptoms. Over the next 6 weeks, they recorded headaches on twice-daily diaries. We conducted time-to-event analyses to evaluate whether these baseline symptoms were associated with headache recurrence. RESULTS: At baseline, 45/98 (46%) participants had poor sleep quality, 51/98 (52%) reported moderate/high stress levels, and 18/98 (18%) had high depressive symptom scores. Over 4,406 person-days, we observed 823 discrete headaches. In multivariable models, the hazard ratios for headache recurrence were: 1.22 (95% CI 1.02, 1.46) for people with baseline poor sleep, 1.12 (95% CI 0.93, 1.35) for those with baseline moderate/high stress compared to lower levels, and 1.31 (95% CI 1.05, 1.65) for the combination of poor sleep and moderate/high stress compared to the combination of good sleep and low stress. There was no association between depression scores and headache risk. CONCLUSION: Among patients with episodic migraine, poor sleep was associated with a higher rate of headache recurrence over the next 6 weeks, especially among those with coexisting moderate/high stress.

Prospective cohort study of routine exercise and headache outcomes among adults with episodic migraine.

OBJECTIVE: To evaluate the association of routine exercise with headache frequency, intensity, and duration among adults with episodic migraine (EM). BACKGROUND: A comprehensive management plan for EM must aim at reducing disability and cost of care; to do so requires optimizing acute and preventive medications, and behavior changes. Prophylactic medication use is associated with adverse events and contraindications with comorbidities. Aerobic exercise is reported to decrease migraine frequency. However, no study has evaluated a potential synergistic relation between regular exercise and preventive medication use among patients with EM. DESIGN AND METHODS: This was a secondary analysis of data from a prospective cohort study of adults with EMs. In that study, adults with EM (using International Classification of Headache Disorders-3 criteria confirmed by study physicians) were recruited from three academic medical centers in Boston, MA. At baseline, participants provided information on exercise, clinical and demographic characteristics, and lifestyle behaviors. We prospectively collected daily information on headaches and health behavior over at least 6 weeks using electronic questionnaires from 94 participants. We assessed the association between baseline self-reported moderate-vigorous exercise at least three times per week, at baseline, and prospectively recorded headache frequency, intensity, and duration. We further assessed whether these associations differed by the prevalent use of prophylactic migraine medication. RESULTS: Data from 94 of 98 eligible participants were used in the analysis as 4 participants had missing data on routine exercise frequency or intensity at baseline. On average, patients who reported moderate-vigorous exercise at least three times per week at enrollment had 1.5 fewer headache days per month (-1.5 headache days/month; 95% confidence interval [CI] -3.1 to 0.1) compared to less exercise; this was not statistically significant (p = 0.066). The association between exercise and headache days per month varied by baseline use of migraine prophylaxis (p-value of interaction = 0.009). Among those who reported regular use of migraine prophylaxis, a report of moderate-vigorous exercise at least three times per week was associated with 5.1 fewer headache days (-5.1: 95% CI -8.2 to -2.0; p = 0.001) compared to those who reported lower levels of exercise. However, among those not using migraine prophylaxis, we observed only 0.4 fewer headache days per month (-0.4: 95% CI -2.2 to 1.3; p = 0.636) associated with moderate-vigorous exercise at least three times/week, a result that was not statistically significant. There was no association of self-reported moderate-vigorous exercise at least three times a week with headache intensity or duration. CONCLUSION: In patients with EM, those who reported moderate-vigorous exercise at least three times per week had fewer headache days per month, though not statistically significant. This association was significantly stronger in those who used prophylactic medication for migraines. Exercise appeared not to be associated with the severity or duration of headaches. Routine moderate-vigorous exercise may be an important adjunctive strategy for improving headache burden in patients eligible for migraine prophylaxis.

The relationship between traffic-related air pollution exposures and allostatic load score among youth with type 1 diabetes in the SEARCH cohort.

OBJECTIVE: We investigated the effects of chronic exposures to particulate and traffic-related air pollution on allostatic load (AL) score, a marker of cumulative biological risk, among youth with type 1 diabetes. RESEARCH DESIGN AND METHODS: Participants were drawn from five clinical sites of the SEARCH for Diabetes in Youth (SEARCH) study (n = 2338). Baseline questionnaires, anthropometric measures, and a fasting blood test were taken at a clinic visit between 2001 and 2005. AL was operationalized using 10 biomarkers reflecting cardiovascular, metabolic, and inflammatory risk. Annual residential exposures to PM2.5 and proximity to heavily-trafficked major roadways were estimated for each participant. Poisson regression models adjusted for sociodemographic and lifestyle factors were conducted for each exposure. RESULTS: No significant associations were observed between exposures to PM2.5 or proximity to traffic and AL score, however analyses were suggestive of effect modification by race for residential distance to heavily-trafficked major roadways (p = 0.02). In stratified analyses, residing <100, 100-<200 and 200-<400 m compared to 400 m or more from heavily-trafficked major roadways was associated with 11%, 26% and 14% increases in AL score, respectively (95% CIs: -4, 29; 9, 45; -1, 30) for non-white participants compared to 6%, -2%, and -2% changes (95% CIs: -2, 15; -10, 7; -8, 6) for white participants. CONCLUSIONS: Among this population of youth with type 1 diabetes, we did not observe consistent relationships between chronic exposures to particulate and traffic-related air pollution and changes in AL score, however associations for traffic-related pollution exposures may differ by race/ethnicity and warrant further examination.

Association Between Sleep Apnea and Blood Pressure Control Among Blacks.

BACKGROUND: Blacks have a high prevalence of hypertension and uncontrolled blood pressure (BP), each of which may be partially explained by untreated sleep apnea. We investigated the association of sleep apnea with uncontrolled BP and resistant hypertension in blacks. METHODS: Between 2012 and 2016, Jackson Heart Sleep Study participants (N=913) underwent an in-home Type 3 sleep apnea study, clinic BP measurements, and anthropometry. Moderate or severe obstructive sleep apnea (OSA) was defined as a respiratory event index ≥15, and nocturnal hypoxemia was quantified as percent sleep time with <90% oxyhemoglobin saturation. Prevalent hypertension was defined as either a systolic BP ≥130 mm Hg or diastolic BP >80mm Hg, use of antihypertensive medication, or self-report of a diagnosis of hypertension. Controlled BP was defined as systolic BP <130 mm Hg and diastolic BP <80 mm Hg; uncontrolled BP as systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg with use of 1 to 2 classes of antihypertensive medication; and resistant BP as systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg with the use of ≥3 classes of antihypertensive medication (including a diuretic) or use of ≥4 classes of antihypertensive medication regardless of BP level. Multinomial logistic regression models were fit to determine the association between OSA severity and uncontrolled BP or resistant hypertension (versus controlled BP) after multivariable adjustment. RESULTS: The analytic sample with hypertension (N=664) had a mean age of 64.0 (SD,10.6) years, and were predominately female (69.1%), obese (58.6%), and college educated (51.3%). Among the sample, 25.7% had OSA, which was untreated in 94% of participants. Overall, 48% of participants had uncontrolled hypertension and 14% had resistant hypertension. After adjustment for confounders, participants with moderate or severe OSA had a 2.0 times higher odds of resistant hypertension (95% confidence interval [CI], 1.14-3.67). Each standard deviation higher than <90% oxyhemoglobin saturation was associated with an adjusted odds ratio for resistant hypertension of 1.25 (95% CI 1.01-1.55). OSA and <90% oxyhemoglobin saturation were not associated with uncontrolled BP. CONCLUSION: Untreated moderate or severe OSA is associated with increased odds of resistant hypertension. These results suggest that untreated OSA may contribute to inadequate BP control in blacks.

Cannabis Use Disorder and Perioperative Outcomes in Major Elective Surgeries: A Retrospective Cohort Analysis.

BACKGROUND: Although cannabis is known to have cardiovascular and psychoactive effects, the implications of its use before surgery are currently unknown. The objective of the present study was to determine whether patients with an active cannabis use disorder have an elevated risk of postoperative complications. METHODS: The authors conducted a retrospective population-based cohort study of patients undergoing elective surgery in the United States using the Nationwide Inpatient Sample from 2006 to 2015. A sample of 4,186,622 inpatients 18 to 65 yr of age presenting for 1 of 11 elective surgeries including total knee replacement, total hip replacement, coronary artery bypass graft, caesarian section, cholecystectomy, colectomy, hysterectomy, breast surgery, hernia repair, laminectomy, and other spine surgeries was selected. The principal exposure was an active cannabis use disorder, as defined by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnostic codes for cannabis dependence and cannabis abuse. The primary outcome was a composite endpoint of in-hospital postoperative myocardial infarction, stroke, sepsis, deep vein thrombosis, pulmonary embolus, acute kidney injury requiring dialysis, respiratory failure, and in-hospital mortality. Secondary outcomes included hospital length of stay, total hospital costs, and the individual components of the composite endpoint. RESULTS: The propensity-score matched-pairs cohort consisted of 27,206 patients. There was no statistically significant difference between patients with (400 of 13,603; 2.9%) and without (415 of 13,603; 3.1%) a reported active cannabis use disorder with regard to the composite perioperative outcome (unadjusted odds ratio = 1.29; 95% CI, 1.17 to 1.42; P < 0.001; Adjusted odds ratio = 0.97; 95% CI, 0.84 to 1.11; P = 0.63). However, the adjusted odds of postoperative myocardial infarction was 1.88 (95% CI, 1.31 to 2.69; P < 0.001) times higher for patients with a reported active cannabis use disorder (89 of 13,603; 0.7%) compared with those without (46 of 13,603; 0.3%) an active cannabis use disorder (unadjusted odds ratio = 2.88; 95% CI, 2.34 to 3.55; P < 0.001). CONCLUSIONS: An active cannabis use disorder is associated with an increased perioperative risk of myocardial infarction.

Corrections for measurement error due to delayed onset of illness for case-crossover designs.

Epidemiologic studies of the short-term effects of ambient particulate matter (PM) on the risk of acute cardiovascular or cerebrovascular events often use data from administrative databases in which only the date of hospitalization is known. A common study design for analyzing such data is the case-crossover design, in which exposure at a time when a patient experiences an event is compared to exposure at times when the patient did not experience an event within a case-control paradigm. However, the time of true event onset may precede hospitalization by hours or days, which can yield attenuated effect estimates. In this article, we consider a marginal likelihood estimator, a regression calibration estimator, and a conditional score estimator, as well as parametric bootstrap versions of each, to correct for this bias. All considered approaches require validation data on the distribution of the delay times. We compare the performance of the approaches in realistic scenarios via simulation, and apply the methods to analyze data from a Boston-area study of the association between ambient air pollution and acute stroke onset. Based on both simulation and the case study, we conclude that a two-stage regression calibration estimator with a parametric bootstrap bias correction is an effective method for correcting bias in health effect estimates arising from delayed onset in a case-crossover study.

Comparison of Invasive and Noninvasive Blood Pressure Measurements for Assessing Signal Complexity and Surgical Risk in Cardiac Surgical Patients.

BACKGROUND: Continuous arterial blood pressure (ABP) is typically recorded by placement of an intraarterial catheter. Recently, noninvasive ABP monitors have been shown to be comparable in accuracy to invasive measurements. In a previous study, we showed that the fluctuations in beat-to-beat ABP measurements were not random variations but had a complex dynamical structure, and that ABP dynamical complexity was inversely associated with surgical risk estimated using the Society of Thoracic Surgeons (STS) index. Dynamical complexity is a mathematical construct that reflects the capacity of a physiological system to adapt to stimuli. The objectives of present study were to: (1) determine whether noninvasive beat-to-beat ABP measurements also exhibit a complex temporal structure; (2) compare the complexity of noninvasive versus invasive ABP time series; and (3) quantify the relationship between the complexity of noninvasive ABP time series and the STS risk scores. METHODS: Fifteen adult patients undergoing coronary artery bypass graft, valve, or combined coronary artery bypass graft/valve surgery were enrolled in this observational study. Preoperative ABP waveforms were simultaneously recorded for ≥15 minutes using a radial artery catheter (invasive) and a continuous noninvasive arterial pressure monitor. Beat-to-beat systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) time series were extracted from the continuous waveforms. Complexity was assessed using the multiscale entropy method. The Wilcoxon signed-rank test was used to compare the mean ranks of indices derived from invasive versus noninvasive ABP time series. Spearman correlation coefficients were used to quantify the relationship between invasive and noninvasive indices. Linear regression analysis was used to quantify the association between each of the complexity indices and the STS risk scores. RESULTS: Beat-to-beat fluctuations in noninvasive ABP measurements were not random but complex; however, their degree of complexity was lower than that of fluctuations in invasively obtained ABP signals (SBP: 7.05 vs 8.66, P < .001; DBP: 7.40 vs 8.41, P < .001; PP: 6.83 vs 8.82, P < .001; and MAP: 7.17 vs 8.68, P < .005). Invasive and noninvasive indices for MSEΣ·slope showed good correlation (rs) (0.53 for SBP, 0.79 for DBP, 0.42 for PP, 0.60 for MAP). The complexity of noninvasive ABP time series (-0.70 [-1.28 to -0.11]; P = .023 for DBP), like that of invasive time series (-0.94 [-1.52 to -0.35]; P = .004 for DBP), was inversely associated with estimated surgical risk in patients undergoing cardiovascular operations. CONCLUSIONS: Our results support the use of noninvasive ABP monitoring in computations of complexity-based indices that correlate with estimated surgical risk.

Changes in nonlinear dynamic complexity measures of blood pressure during anesthesia for cardiac surgeries using cardio pulmonary bypass.

Nonlinear complexity measures computed from beat-to-beat arterial BP dynamics have shown associations with standard cardiac surgical risk indices. They reflect the physiological adaptability of a system and has been proposed as dynamical biomarkers of overall health status. We sought to determine the impact of anesthetic induction and cardiopulmonary bypass (CPB) upon the complexity measures computed from perioperative BP time series. In this prospective, observational study, 300 adult patients undergoing cardiac surgery were included. Perioperative period was divided as: (1) Preoperative (PreOp); (2) ORIS-induction to sternotomy; (3) ORSB- sternotomy to CPB; (4) ORposB-post CPB and within 30 min before leaving OR and (5) postoperative phase (PostOp)-initial 30 min in the cardiac surgical intensive care unit. BP waveforms for systolic (SAP), diastolic (DAP), mean arterial pressure (MAP) and pulse pressure (PP) were recorded, and their corresponding complexity index (MSE∑) was calculated. Significant decrease in MSE∑ from Preop to PostOp phases was observed for all BP time series. Maximum fall was seen during post anesthetic induction (ORIS) phase. Mild recovery during the subsequent phases was observed but they never reached the baseline values. In an exploratory analysis, preoperative MSE∑ showed a significant correlation with postoperative length of ICU stay. Blood pressure complexity varies at different time points and is not fixed for a given individual. Preoperative BP Complexity decreased significantly following anesthetic induction and did not recover to baseline until 30 min after surgery. Prevention of this significant fall may offer restoration of MSE∑ throughout surgery. Furthermore, preoperative BP complexity needs to be explored as a predictor of major postoperative adverse events by itself or in addition with the current risk indices.

Ambient air pollution exposure and risk and progression of interstitial lung abnormalities: the Framingham Heart Study.

BACKGROUND: Ambient air pollution accelerates lung function decline among adults, however, there are limited data about its role in the development and progression of early stages of interstitial lung disease. AIMS: To evaluate associations of long-term exposure to traffic and ambient pollutants with odds of interstitial lung abnormalities (ILA) and progression of ILA on repeated imaging. METHODS: We ascertained ILA on chest CT obtained from 2618 Framingham participants from 2008 to 2011. Among 1846 participants who also completed a cardiac CT from 2002 to 2005, we determined interval ILA progression. We assigned distance from home address to major roadway, and the 5-year average of fine particulate matter (PM2.5), elemental carbon (EC, a traffic-related PM2.5 constituent) and ozone using spatio-temporal prediction models. Logistic regression models were adjusted for age, sex, body mass index, smoking status, packyears of smoking, household tobacco exposure, neighbourhood household value, primary occupation, cohort and date. RESULTS: Among 2618 participants with a chest CT, 176 (6.7%) had ILA, 1361 (52.0%) had no ILA, and the remainder were indeterminate. Among 1846 with a preceding cardiac CT, 118 (6.4%) had ILA with interval progression. In adjusted logistic regression models, an IQR difference in 5-year EC exposure of 0.14 µg/m3 was associated with a 1.27 (95% CI 1.04 to 1.55) times greater odds of ILA, and a 1.33 (95% CI 1.00 to 1.76) times greater odds of ILA progression. PM2.5 and O3 were not associated with ILA or ILA progression. CONCLUSIONS: Exposure to EC may increase risk of progressive ILA, however, associations with other measures of ambient pollution were inconclusive.

Association of outdoor temperature with lung function in a temperate climate.

Acute exposure to cold dry air is a trigger of bronchoconstriction, but little is known about how daily outdoor temperature influences lung function.We investigated associations of temperature from a model using satellite remote sensing data with repeated measures of lung function among 5896 participants of the Framingham Heart Study Offspring and Third Generation cohorts residing in the Northeastern US. We further tested if temperature modified previously reported associations between pollution and lung function. We constructed linear mixed-effects models, and assessed departures from linearity using penalised splines.In fully adjusted linear models, 1-, 2- and 7-day average temperatures were all associated with lower lung function: each 5°C higher previous-week temperature was associated with a 20 mL lower (95% CI -34---6) forced expiratory volume in 1 s. There was significant effect modification by season: negative associations of temperature and lung function were present in winter and spring only. Negative associations between previous-day fine particulate matter and lung function were present during unseasonably warm but not unseasonably cool days, with a similar pattern for other pollutants.We speculate that temperature-related differences in lung function may be explained by behavioural changes on relatively warm days, which may increase outdoor exposures.

Radiographic pulmonary vessel volume, lung function and airways disease in the Framingham Heart Study.

Radiographic abnormalities of the pulmonary vessels, such as vascular pruning, are common in advanced airways disease, but it is unknown if pulmonary vascular volumes are related to measures of lung health and airways disease in healthier populations.In 2388 participants of the Framingham Heart Study computed tomography (CT) sub-study, we calculated total vessel volumes and the small vessel fraction using automated CT image analysis. We evaluated associations with measures of lung function, airflow obstruction on spirometry and emphysema on CT. We further tested if associations of vascular volumes with lung function were present among those with normal forced expiratory volume in 1 s and forced vital capacity.In fully adjusted linear and logistic models, we found that lower total and small vessel volumes were consistently associated with worse measures of lung health, including lower spirometric volumes, lower diffusing capacity and/or higher odds of airflow obstruction. For example, each standard deviation lower small vessel fraction (indicating more severe pruning) was associated with a 37% greater odds of obstruction (OR 1.37, 95% CI 1.11-1.71, p=0.004). A similar pattern was observed in the subset of participants with normal spirometry.Lower total and small vessel pulmonary vascular volumes were associated with poorer measures of lung health and/or greater odds of airflow obstruction in this cohort of generally healthy adults without high burdens of smoking or airways disease. Our findings suggest that quantitative CT assessment may detect subtle pulmonary vasculopathy that occurs in the setting of subclinical and early pulmonary and airways pathology.

The Case-Crossover Design for Drug-Drug Interactions: Considerations for Implementation.

BACKGROUND: The case-crossover design may be useful for evaluating the clinical impact of drug-drug interactions in electronic healthcare data; however, experience with the design in this context is limited. METHODS: Using US healthcare claims data (1994-2013), we evaluated two examples of interacting drugs with prior evidence of harm: (1) cytochrome P450 (CYP)3A4-metabolized statins + clarithromycin or erythromycin and rhabdomyolysis; and (2) clopidogrel + fluoxetine or fluvoxamine and ischemic events. We conducted case-crossover analyses with (1) a three-parameter model with a product term and a six-parameter saturated model that distinguished initiation order of the two drugs; and (2) with or without active comparators. RESULTS: In the statin example, the three-parameter model produced estimates consistent with prior evidence with the active comparator (product term odds ratio [OR] = 2.05, 95% confidence interval [CI] = 1.00, 4.23) and without (OR = 1.99, 95% CI = 1.04, 3.81). In the clopidogrel example, this model produced results opposite of expectation (OR = 0.78, 95% = 0.68, 0.89), but closer to what was observed in prior studies when active comparator was used (OR = 1.03, 95% CI = 0.90, 1.19). The saturated model revealed heterogeneity of estimates across strata and considerable confounding; strata with concordant clopidogrel exposure likely produced the least biased estimates. CONCLUSION: The three-parameter model assumes a common drug-drug interaction effect, whereas the saturated model is useful for identifying potential effect heterogeneity or differential confounding across strata. Restriction to certain strata or use of an active comparator may be necessary in the presence of within-person confounding.

Short-term exposure to ambient air pollution and circulating biomarkers of endothelial cell activation: The Framingham Heart Study.

BACKGROUND: Short-term exposure to air pollution has been associated with cardiovascular events, potentially by promoting endothelial cell activation and inflammation. A few large-scale studies have examined the associations and have had mixed results. METHODS: We included 3820 non-current smoking participants (mean age 56 years, 54% women) from the Framingham Offspring cohort examinations 7 (1998-2001) and 8 (2005-2008), and Third Generation cohort examination 1 (2002-2005), who lived within 50 km of a central monitoring station. We calculated the 1- to 7-day moving averages of fine particulate matter (PM2.5), black carbon (BC), sulfate (SO42-), nitrogen oxides (NOx), and ozone before examination visits. We used linear mixed effect models for P-selectin, monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1, lipoprotein-associated phospholipase A2 activity and mass, and osteoprotegerin that were measured up to twice, and linear regression models for CD40 ligand and interleukin-18 that were measured once, adjusting for demographics, life style and clinical factors, socioeconomic position, time, and meteorology. RESULTS: We found negative associations of PM2.5 and BC with P-selectin, of ozone with MCP-1, and of SO42- and NOx with osteoprotegerin. At the 5-day moving average, a 5 µg/m3 higher PM2.5 was associated with 1.6% (95% CI: - 2.8, - 0.3) lower levels of P-selectin; a 10 ppb higher ozone was associated with 1.7% (95% CI: - 3.2, - 0.1) lower levels of MCP-1; and a 20 ppb higher NOx was associated with 2.0% (95% CI: - 3.6, - 0.4) lower levels of osteoprotegerin. CONCLUSIONS: We did not find evidence of positive associations between short-term air pollution exposure and endothelial cell activation. On the contrary, short-term exposure to higher levels of ambient pollutants were associated with lower levels of P-selectin, MCP-1, and osteoprotegerin in the Framingham Heart Study.