The Effects of Traditional Acupuncture on Mechanisms of Coronary Heart Disease

A. SPECIFIC AIMS Sudden and unexpected cardiac death remains a significant problem in
patients with established coronary heart disease (CHD), and accounts for 30% of deaths in
this group (~150,000 deaths annually) despite recognition and treatment of their disease.
These sudden deaths are due to myocardial infarction and ischemic or nonischemically mediated
arrythmias. Traditional risk factors do not completely account for the excess of CHD deaths.
Although treatment of cardiac risk factors, such as hyperlipidemia, has been shown to
significantly reduce cardiac events in populations with established coronary heart disease
(e.g. by 34% in the Scandinavian Simvastatin Survival Study1) a majority of patients continue
to have sudden and unexpected cardiac events including sudden cardiac death. Indeed, up to
50% of patients with established CHD will have recurrent events despite aggressive management
of traditional risk factors such as hyperlipidemia, tobacco use and hypertension. This
suggests that additional risk factors or mechanisms participate in the pathophysiological
cascade underlying acute CHD events.

A large body of evidence implicates psychosocial stress as a risk factor and trigger for
myocardial ischemia, infarction and sudden cardiac death, yet the specific mechanisms(s) of
this relationship remain under investigation.2-9 The mechanisms may include hemodynamic,
hemostatic and neuronally mediated effects on the cardiovascular system. Specifically they
may include a prominent role of the cardiac autonomic nervous system, including the
sympathetic nervous system (SNS) and parasympathetic nervous system (PNS).10 Indeed, cardiac
arrhythmias have been implicated both as a risk factor and an etiology for sudden cardiac
death, suggesting that alteration of cardiac autonomic nervous system tone may provide an
opportunity for reducing acute cardiac events and sudden cardiac death. Prior work by
ourselves and others has also demonstrated that sympathetic activation from psychosocial
stress results in vascular constriction that, in the presence of impaired nitric oxide (NO)
production and endothelial dysfunction, contributes to myocardial ischemia and adverse
cardiac events, including sudden death. 6,8,11-15 Traditional Acupuncture (TA) is a
Complementary and Alternative Medicine (CAM) practice with documented effects of improving
physiologic imbalances and reducing psychosocial stress. For example, the TA technique has
been shown, to significantly reduce mental stress in humans16, hypertension in an animal
model17 and angina pectoris in CHD patients.18 These changes are consistent with the
hypothesis that the TA technique directly alters autonomic nervous system tone, likely by
reducing SNS activity, and possibly also by increasing PNS activity. We also hypothesize that
TA may beneficially alter CHD indirectly by reducing psychosocial stress. Either of these
hypotheses suggests that this CAM practice may serve as a complement or alternative to
medical treatment for the prevention of acute cardiac events and sudden cardiac death.

We propose to evaluate the effect of TA on arterial vasomotor function and autonomic nervous
system tone, two physiologic variables involved in the pathophysiological cascade underlying
acute cardiac events and sudden death in CHD patients. To test for both the hypothesized
direct and indirect effects of this CAM modality, we propose to compare an active TA
intervention to two control groups: 1) an Alternative Acupuncture control group, and 2) a
waiting control group, in patients with CHD.

Primary Aim

1. To assess effects of the TA technique (compared to Alternative Acupuncture and waiting
control) on cardiac autonomic nervous system tone, as measured by heart rate variability
(HRV) using Holter monitoring.

Secondary Aims

2. To assess effects of the TA technique (compared to Alternative Acupuncture and waiting
control) on CHD variables including a marker of inflammation (high sensitivity C
reactive protein), symptoms (Seattle Angina Questionnaire), functional status (Duke
Activity Status Inventory), blood lipoproteins, and blood pressure.

3. To assess effects of the TA technique (compared to Alternative Acupuncture and waiting
control) on measures of perceived psychological stress, depression, hostility, anxiety,
social support, and quality of life.

Exploratory Aims

4. To estimate effect size of the TA technique (compared to Alternative Acupuncture and
waiting control) on arterial vasomotor dysfunction, as measured by mental
stress-brachial artery reactivity testing (BART) using high frequency ultrasound.

The results of the study will: a) provide an improved understanding of the hypothesized
beneficial physiological and psychological effects of this CAM practice, and b) serve as
potential pilot data for a multi-center TA proposal to evaluate the impact of TA on acute
cardiac events, including sudden cardiac death.

Inclusion Criteria:

- Age > 21 years

- Male or female

- Local residence

- Medically able to participate

- CAD by MI, CABG, PTCA, or stroke (>3 months prior), or angiographic evidence >50%
epicardial coronary artery stenosis in at least one coronary artery

- Consent and referring MD approval

Exclusion Criteria:

- Comorbid disease precluding survival during study

- MI, unstable angina, CABG, PTCA or stroke within 3 months*

- HIV infection, chronic or active hepatitis or other blood-borne illness

- Cognitive, psychological or substance abuse-related impairment, as clinically assessed

- Atrial fibrillation, predominant pacemaker rhythm, significant conduction system
disease, or automatic internal defibrillator*

- Significant valvular heart disease*

- Class III or IV heart failure*

- Renal or liver failure, as clinically assessed

- Participating in TA, or formal psychosocial stress management program

- Participation in another trial.