Heavy physical exertion, emotional stress, heavy meals, and respiratory infection transiently increase the risk of myocardial infarction, sudden cardiac death, and stroke; however, it remains uncertain how to use this information for disease prevention. We determined whether it was feasible for those with either risk factors for cardiovascular disease (CVD) or known CVD to take targeted medication for the hazard duration of the triggering activity to reduce their risk. After a run-in of 1 month, 20 subjects (12 women and 8 men) aged 68.6 years (range 58 to 83) recorded for 2 months all episodes of physical and emotional stress, heavy meal consumption, and respiratory infection. For each episode, the subjects were instructed to take either aspirin 100 mg and propranolol 10 mg (for physical exertion and emotional stress) or aspirin 100 mg alone (for respiratory infection and heavy meal consumption) and to record their adherence. Adherence with taking the appropriate medication was 86% according to the diary entries, with 15 of 20 subjects (75%) achieving ≥80% adherence. Propranolol taken before exertion reduced the peak heart rate compared with similar exercise during the run-in period (118 ± 21 vs 132 ± 16 beats/min, p = 0.016). Most subjects (85%) reported that it was feasible to continue taking the medication in this manner. In conclusion, it is feasible for those with increased CVD risk to identify potential triggers of acute CVD and to take targeted therapy at the time of these triggers.
Heavy physical exertion, acute emotional stress, respiratory infection, and the consumption of heavy meals transiently increase the relative risk of acute myocardial infarction (MI), sudden death, and stroke by 2- to 10-fold over the basal risk. However, it remains unclear how this information can be used for the consideration of prevention. The current preventative medication strategies emphasize long-term daily therapy for risk factors such as hypertension and hypercholesterolemia. However, this approach does not specifically address the added risk posed by the acute triggers. Just as supplemental strategies have been recommended for episodic treatment of paroxysmal supraventricular arrhythmias or exacerbation of asthma, we have proposed a strategy of triggered acute risk prevention, for which 1 potential approach would be for the patient to take targeted preventive medication acutely at the time of the potential trigger. However, before such an approach could be considered clinically applicable, several steps are required, including determining the feasibility. We have previously demonstrated that such an approach is feasible and acceptable to healthy subjects. The goals of the present study were to determine whether higher risk subjects with risk factors for, or known, cardiovascular disease (CVD) could reliably identify and document episodes of heavy physical exertion, emotional stress, heavy meals, and respiratory infection and take the designated medication (propranolol and/or aspirin) at the time of the trigger. We also sought to determine whether this approach would be practical and acceptable to the participants.
Methods
The subjects provided written informed consent, and the institutional human research ethics committee approved the present study. Participants were excluded if they had contraindications to aspirin or β blockers; if they had asthma, diabetes, a peptic ulcer, a heart rate at rest of <60 beats/min; if they were not in sinus rhythm or had a systolic blood pressure <110 mm Hg; or if they were taking regular heart rate-lowering medication (e.g., β blockers, heart rate-lowering calcium channel blockers, digoxin or ivabradine) or an antiplatelet or anticoagulant other than aspirin. Other concomitant medications were allowed. Two subjects were taking antidepressants, and 5 were taking analgesics (aspirin by 3 and paracetamol by 2).
During a 1-month run-in period, the subjects were instructed by a research nurse on how to identify and record specific triggers in a pocket-size event diary. Using scales we have previously used, the subjects recorded only the more severe episodes of physical activity and emotional stress that have been associated with an increased relative risk of MI. The subjects recorded exertion, anger, anxiety, heavy meal consumption, and respiratory infections, as defined in Table 1 . The participants were encouraged to maintain their usual daily activities and behavior. In the first week, the subjects were telephoned at least once by an investigator to address any questions and remained available throughout the study period. After the run-in period, the diaries were reviewed, and participants who had complied with the protocol progressed to the 2-month study period. In addition to completing the event diary, the subjects were instructed to take the following oral medications at the onset or within 30 minutes before an anticipated stressor: physical activity, aspirin (100 mg) plus propranolol (10 mg); anger or anxiety, aspirin plus propranolol; heavy meal, aspirin only; and respiratory infection, aspirin only. The subjects recorded in their diary whether and when they had taken the study medication. For one 24-hour period during the run-in and study phases, the participants wore a heart rate monitor, during which they were instructed to perform a physical activity that was the same in both the run-in and study phases. During the study phase, they took aspirin and propranolol 30 minutes before the monitored activity. Two subjects were identified during the run-in period who exercised ≥4 times weekly and were classified as regular exercisers. Because heavy exertion in regular exercisers has been associated with only a small increase in relative risk, these 2 regular exercisers recorded each episode but were instructed not to take medication for exertion, except during the monitored period. Adherence with taking the medication for triggers was assessed using the diary. A pill count was completed at study completion. The research nurse asked for any potential side effects of the medication as part of the telephone calls during the study period and at its completion. During the physical stress performed while monitored, the subjects were asked if they had noted any difference from when they normally performed the activity.
Exertion chart
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∗ Only these levels of physical and emotional stress were entered in the diaries.
Of the 26 subjects recruited, 6 withdrew before the study phase. Of these 6 subjects, 2 decided they did not want to take the study medication, 1 experienced a mechanical fall during the run-in period and did not wish to continue, 1 was already taking a β blocker, which had not been recognized at enrollment, and 2 were withdrawn by the investigators because they did not accurately complete the run-in phase. The subjects who withdrew were 4 men and 2 women of average age (75.0 years, range 61 to 81). No subjects withdrew once the study phase had begun.
A comparison of the peak and average heart rate during exercise between the run-in and study phases was performed using a paired t test (Statistical Package for Social Sciences, version 18, SPSS, Chicago, Illinois). p Values <0.05 were considered statistically significant.
Results
Of the 20 subjects, 12 women and 8 men, with an average age of 68.6 years (range 58 to 83), completed the study period ( Table 2 ). During the 2-month study period, they reported 138 physical exertion events, 97 heavy meals, 10 anger events, 38 anxiety events, and 1 respiratory infection. Almost all (94%) of the episodes of physical exertion were anticipated activities such as speed walking, running, training, and gym workouts. The 9 unanticipated events included hurrying to collect children from child care, unexpected gardening, and walking up hills or stairs. Work and family conflict and deadlines, health concerns, and planning social gatherings were the leading causes of the episodes of anger and anxiety. During the study period, 6 subjects (30%) reported ≥1 anger event. All anger events were unanticipated. Twelve subjects (60%) reported ≥1 anxiety event, 56% of which were unanticipated. Most subjects (90%) in the study period reported ≥1 heavy meal, and 1 subject (5%) reported a respiratory infection.
| Age (yrs) | Gender | HT | HC | FH | CAD | ACE or ATII | Aspirin | Statin | Calcium Blockers |
|---|---|---|---|---|---|---|---|---|---|
| 55 | F | – | Yes | – | – | – | – | – | – |
| 58 | M | Yes | – | Yes | – | Yes | Yes | Yes | – |
| 59 | M | – | Yes | Yes | Yes | – | Yes | Yes | – |
| 63 | F | – | Yes | Yes | – | – | – | Yes | – |
| 64 | F | Yes | Yes | – | – | Yes | – | – | – |
| 64 | M | – | – | Yes | – | – | Yes | – | – |
| 66 | F | – | Yes | Yes | – | – | Yes | Yes | – |
| 67 | F | – | Yes | – | – | – | – | – | – |
| 67 | F | Yes | Yes | Yes | – | Yes | – | Yes | – |
| 68 | M | – | Yes | – | – | – | – | – | – |
| 68 | F | – | Yes | – | – | – | Yes | – | – |
| 69 | F | – | Yes | – | – | – | – | – | – |
| 70 | F | Yes | Yes | – | – | Yes | Yes | Yes | Yes |
| 72 | M | – | Yes | – | – | – | Yes | Yes | – |
| 73 | F | Yes | – | Yes | – | Yes | – | – | – |
| 74 | F | – | Yes | – | – | – | Yes | Yes | – |
| 77 | M | – | Yes | – | – | – | – | Yes | – |
| 77 | M | – | Yes | – | – | – | – | Yes | – |
| 78 | F | – | – | Yes | – | – | Yes | – | – |
| 83 | M | – | Yes | – | Yes | Yes | Yes | Yes | – |
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