Gail MacCallum

Traffic related pollution and heart rate variability in a panel of elderly subjects

Background: Particulate air pollution has been associated with increased cardiovascular deaths and hospital admissions. To help understand the mechanisms, the types of particles most involved, and the types of persons most susceptible, the association between exposure to summertime air pollution and heart rate variability (HRV) was examined in a panel study of 28 elderly subjects. Methods: Subjects were seen once a week for up to 12 weeks and HRV (SDNN, r-MSSD, PNN50, low frequency/high frequency ratio (LFHFR)) was measured for approximately 30 minutes at each session using a defined protocol. Temperature, day of the week, and hour of the day were controlled, and dummy variables for each subject were controlled for subject specific risk factors. Results: PM2.5 was associated with r-MSSD (−10.1% change for an interquartile range (IQR) increase in exposure (95% CI −2.8 to −16.9)) and PNN50, but stronger associations were seen with black carbon, an indicator of traffic particles, which was also associated with SDNN (−4.6% per IQR (95% CI −2.0 to −7.2)) and LFHFR. Secondary particles were more weakly associated with r-MSSD, as was ozone. No associations were seen with SO2 or NO2. CO had similar patterns of association to black carbon, which disappeared after controlling for black carbon. Black carbon had a substantially higher effect on SDNN in subjects who had had a previous myocardial infarction (−12.7%, 95% CI −5.7 to −19.25). Conclusions: Particles, especially from traffic, are associated with disturbances of autonomic control of the heart.

Subsets of ambulatory myocardial ischemia based on heart rate activity. Circadian distribution and response to anti-ischemic medication. The Angina and Silent Ischemia Study Group (ASIS)

BACKGROUND Identification of whether episodes of ambulatory ischemia are caused by increases in myocardial oxygen demand or to episodic coronary vasoconstriction in patients with stable coronary disease may be important to guide selection of optimal anti-ischemic therapy and to gain insight into mechanisms responsible for adverse cardiac events. METHODS AND RESULTS Mean minute heart rate activity during ambulatory ECG (AECG) monitoring was determined for 50 patients treated with propranolol, diltiazem, nifedipine, or placebo in a randomized, double-blind, crossover trial. Periods of heart rate increases of various magnitudes and durations and starting at various baseline heart rates on each therapy were identified throughout each 48-hour AECG recording, and the proportion of these periods associated with an ischemic episode was determined. The circadian variation of ischemic episodes categorized by the presence or absence of an increase in heart rate was analyzed. Eighty-one percent of ischemic episodes were preceded by an increase in heart rate > or = 5 beats per minute. The likelihood of developing ischemia associated with a heart rate increase was proportional to the magnitude and duration of the heart rate increase and the baseline heart rate before the increases in heart rate: likelihood ranged from 4% when the heart rate increased 5-9 beats per minute and lasted < 10 minutes to 60% when the heart rate increased > or = 20 beats per minute and lasted > or = 40 minutes. The likelihoods of developing ischemia based on changes in the heart rate variables were similar for each of the therapies. Propranolol therapy significantly reduced the magnitude and duration of heart rate increase and the baseline heart rate compared with therapy with placebo, diltiazem, or nifedipine (P < .001). Ischemic episodes associated with a heart rate increase displayed a daytime peak, whereas ischemia occurring without a heart rate increase occurred evenly throughout the day. Propranolol reduced the proportion of heart rate-related ischemic episodes and increased the proportion of non-heart rate-related episodes compared with placebo (P < .02), and nifedipine exerted the opposite effect (P = .005). Multivariate analysis indicated that the probability of developing ischemia was strongly associated with heart rate variables and was unaffected by time of day. CONCLUSIONS Most episodes of ambulatory ischemia are associated with a preceding period of increased heart rate. The likelihood of developing ischemia is predicted by heart rate variables and unaffected by time of day. Anti-ischemic efficacy is generally a result of the medications efficacy in reducing heart rate variables. A minority of ischemic episodes are not associated with preceding periods of increased heart rate, may be caused by episodic coronary vasoconstriction, and are more effectively reduced by nifedipine than propranolol.

Air Pollution and ST-Segment Depression in Elderly Subjects

Increased levels of daily ambient particle pollution have been associated with increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the traffic-related component of particles. We investigated associations between ambient pollution and ST-segment levels in a repeated-measures study including 269 observations on 24 active Boston residents 61–88 years of age, each observed up to 12 times from June through September 1999. The protocol involved continuous Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5 min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing. Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile change in BC. We calculated the average ST-segment level, referenced to the P-R isoelectric values, for each portion of the protocol. The mean BC level in the previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment depression in most portions of the protocol, but the effect was strongest in the postexercise periods. During post-exercise rest, an elevated BC level was associated with −0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p = 0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased risk of ST-segment depression ≥0.5 mm among those with at least one episode of that level of ST-segment depression. Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inflammation, is associated with increased exposure to particles whose predominant source is traffic.

Prognostic Significance of Myocardial Ischemia Detected by Ambulatory Electrocardiography, Exercise Treadmill Testing, and Electrocardiogram at Rest to Predict Cardiac Events by One Year (The Asymptomatic Cardiac Ischemia Pilot (ACIP) Study)

Myocardial ischemia identified by ambulatory electrocardiography (AECG), exercising treadmill testing, (ETT), or 12-lead electrocardiogram at rest is associated with an adverse prognosis, but the effect of improving these ischemic manifestations by treatment on outcome is unknown. The Asymptomatic Cardiac Ischemia Pilot (ACIP) study was a National Heart, Lung, and Blood Institute funded study to determine the feasibility of conducting a large-scale prognosis study and to assess the effect of 3 treatment strategies (angina-guided strategy, AECG ischemia-guided strategy, and revascularization strategy) in reducing the manifestations of ischemia as indicated by AECG and ETT. The study cohort for this database study consisted of 496 randomized patients who performed the AECG, ETT, and 12-lead electrocardiogram at rest at both the qualifying and week 12 visits. The effect of modifying ischemia by treatment on the incidence of cardiac events (death, myocardial infarction, coronary revascularization procedure, or hospitalization for an ischemic event) at 1 year was examined. In the 2 medical treatment groups (n = 328) there was an association between the number of ambulatory electrocardiographic ischemic episodes at the qualifying visit and combined cardiac events at 1 year (p = 0.003). In the AECG ischemia-guided patients there was a trend associating greater reduction in the number of ambulatory electrocardiographic ischemia episodes with a reduced incidence of combined cardiac events (r = -0.15, p = 0.06). In the revascularization strategy patients this association was absent. In the medical treatment patients the exercise duration on the baseline ETT was inversely associated with an adverse prognosis (p = 0.02). The medical treatment strategies only slightly improved the exercise time and the exercise duration remained of prognostic significance. In the revascularization group strategy patients this association was absent. Thus, myocardial ischemia detected by AECG and an abnormal ETT are each independently associated with an adverse cardiac outcome in patients subsequently treated medically.

Personal coronary risk profiles modify autonomic nervous system responses to air pollution

Objective: We investigated whether PM2.5-mediated autonomic modulation depends on individual coronary risk profiles. Methods: Five-minute average heart rate (HR) and heart rate variability (HRV, including standard deviation of normal-to-normal intervals [SDNN], square root of the mean squared differences of successive NN intervals [rMSSD], high frequency [HF]) were measured from 24-hour ambulatory electrocardiograms, and personal PM2.5 exposures were monitored in a prospective study of 10 male boilermakers (aged 34.3 ± 8.1 years). We used the Framingham score to classify individuals into low (score = 1–3) and high (score = 5–6) risk categories. Mixed-effect models were used for statistical analyses. Results: Each 1-mg/m3 increase in the preceding 4-hour moving average PM2.5 was associated with HR increase (5.3 beats/min) and HRV reduction (11.7%, confidence interval [CI] = 6.2–17.1% for SDNN; 11.1%, CI = 3.1–19.1% for rMSSD; 16.6%, CI = 1.5–31.7% for HF). Greater responses (2- to 4-fold differences) were observed in high-risk subjects than in low-risk subjects. Conclusions: Our study suggests that adverse autonomic responses to metal particulate are aggravated in workers with higher coronary risk profiles.

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study: Relationship Between Exercise-Induced and Ambulatory Ischemia in Patients With Stable Coronary Disease

BACKGROUND We investigated whether the presence and frequency of asymptomatic ischemic episodes recorded during ambulatory ECG (AECG) monitoring could be predicted on the basis of clinical characteristics or exercise treadmill test (ETT) performance in patients with stable coronary disease and whether the estimate of ischemia severity was similar between the AECG and ETT. METHODS AND RESULTS Patients screened for the Asymptomatic Cardiac Ischemia Pilot (ACIP) study were selected for the current analysis if data were available from 48-hour AECG monitoring as well as from an ETT during which the patient developed > or = 1-mm ST-segment depression. Exercise ECG data were available for 143 of the 910 patients without ischemic episodes and for 659 of the 910 patients with ischemic episodes during AECG monitoring. Angina was more frequent among patients with ambulatory ischemic episodes than among patients without such ischemia (P < .001). Patients with AECG ischemia had a consistently more marked ischemic response on the ETT than patients without AECG ischemia; patients likely to have AECG ischemia could be predicted on the basis of ETT performance characteristics. However, the correlation coefficients between the severity of ischemia estimated by ETT and by AECG were small. CONCLUSIONS There are significant relations between ischemia detected by AECG monitoring and by ETT, but the relations are limited, indicating that the two tests are not redundant to characterize coronary patients. A larger study investigating the prognostic significance of the ischemia identified by each modality, with follow-up for clinical events, will be necessary to determine the most appropriate methods to evaluate patients with stable coronary disease.

Effects of therapy with nifedipine GITS or atenolol on mental stress-induced ischemic left ventricular dysfunction ☆

OBJECTIVES We sought to determine the effect of nifedipine gastrointestinal therapeutic system (GITS) or atenolol on ischemic left ventricular dysfunction induced by mental stress. BACKGROUND The efficacy of conventional antianginal therapy in preventing myocardial ischemia induced by mental stress is unknown. METHODS Nifedipine GITS, atenolol and placebo were administered to 15 subjects with stable angina in a double-blind crossover trial. Subjects underwent a series of mental stressors at the end of each treatment. Radionuclide ventriculography was performed at baseline and at peak mental stress. Other measured variables included time to ischemia on exercise treadmill testing, ischemia on 48-h ambulatory electrocardiogram (ECG) monitoring, and resting and mental stress-induced levels of plasma catecholamines, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 and platelet aggregability. RESULTS Mental stress resulted in a significant increase in plasma epinephrine and norepinephrine levels during each treatment phase. Atenolol therapy was associated with lower baseline and postmental stress rate-pressure product compared with nifedipine or placebo. Therapy with either nifedipine GITS or atenolol prevented the development of wall-motion abnormalities and the decline in regional ejection fraction (EF) in the segment with the largest deterioration in wall motion during placebo therapy. Both medications prevented the decrease in global EF in subjects who demonstrated at least a 5% fall in global EF on placebo therapy. No therapy exerted a statistically significant benefit on exercise performance or frequency of ischemia during ambulatory ECG monitoring. CONCLUSIONS Both nifedipine GITS and atenolol are effective at preventing mental stress-induced wall-motion abnormalities, although the mechanisms may be different.