Relation of Anemia to Low Heart Rate Variability in Patients With Coronary Heart Disease (from the Heart and Soul Study)

Abstract

We examined the association between anemia (hemoglobin ≤12 g/dl) and 6 indexes of heart rate variability (HRV) as measured by 24-hour ambulatory electrocardiography in a cross-sectional study of 874 outpatients who had stable coronary heart disease. Of 90 participants who had anemia, 29% to 41% had low HRV, defined as the lowest quartile of each HRV index, compared with 23% to 25% of the 784 participants who did not have anemia (comparison p values <0.05 for all HRV indexes except high-frequency power). With the exception of high-frequency power, each 1 g/dl decrease in hemoglobin was associated with increased odds of having low HRV. This association remained strong after adjustment for potential confounding variables, including ischemia, left ventricular mass, left ventricular ejection fraction, and diastolic dysfunction. Thus, anemia is associated with low HRV in ambulatory patients who have stable coronary heart disease. Low HRV could potentially mediate the association of anemia with increased cardiac risk.Several small studies have associated anemia due to vitamin B12 deficiency, 1,2 thalassemia, 3 and sickle cell anemia 4 with low heart rate variability (HRV). However, no study has examined whether anemia is associated with HRV in patients who have heart disease. Several studies have shown that low HRV independently predicts sudden cardiac death and overall mortality in patients who have heart disease, [5][6][7][8][9][10] suggesting that low HRV may contribute to the adverse cardiac outcomes associated with anemia. We hypothesized that anemia is associated with an imbalance of cardiac autonomic tone as measured by low HRV in patients who have coronary heart disease (CHD). To determine whether anemia is associated with HRV, we measured hemoglobin and HRV in a cross-sectional study of 874 ambulatory patients who had stable CHD.The Heart and Soul Study is a prospective cohort study of psychosocial factors and health outcomes in patients who have CHD. Details regarding our methods have been previously published. 11 Outpatients who had documented CHD were recruited from 2 veterans affairs medical centers (San Francisco VA Medical Center, San Francisco, California, and the VA Palo Alto Health Care System, Palo Alto, California), 1 university medical center (University of California, San Francisco, California), and 9 public health clinics in the Community Health Network of San Francisco. Patients were eligible to participate if they had ≥1 of the following: a history of myocardial infarction, angiographic evidence of ≥50% stenosis in ≥1 coronary vessel, previous evidence of exercise-induced ischemia by treadmill or nuclear testing, a history of coronary revascularization, or a diagnosis of CHD by an internist or cardiologist (based on NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript a positive angiographic or exercise treadmill test result in >98% of cases). Patients were excluded if they were unable to walk 1 block or were planning to move from the local area within 3 years.Betw...

The Altered Autonomic Nervous System Activity in Iron Deficiency Anemia

“…Moreover, both sympathetic and parasympathetic components of HRV were significantly lower in anemic patients with vitamin B 12 deficiency (Sozen et al 1998) which may suggest that anemia itself may be a cause of autonomic dysfunction. Gehi et al (2005) also stated that anemia-low HRV association was still strong enough after adjustment of other factors such as left ventricular mass and ejection fraction in stable coronary artery disease patients Degree of anemia was suggested to correlate with the progression of autonomic dysfunction in anemic patients with familial amyloidotic polyneuropathy (Asahara et al 1993). Furthermore, elevations in plasma catecholamine and α 2 -receptor density levels as previously reported by Muller et al (1991) also support the high sympathetic activity in anemic patients.…”

Gene-trapped mouse embryonic stem cell-derived cardiac myocytes and human genetics implicate AKAP10 in heart rhythm regulation

“…Data were obtained from patients with stable coronary heart disease enrolled in the Heart and Soul Study (27,28); 682 participants underwent three-channel, 24-h ambulatory ECG monitoring, standardized exercise treadmill testing, and AKAP10 I646V genotyping. For this analysis, we excluded 54 participants who were not in sinus rhythm and 506 participants who were taking antihypertensive medications that affect HR or HRV, leaving 122 participants (mean age, 64 yr; 22% women).…”

“…This cohort included 46 (38%) 646I homozygotes, 26 (21%) 646V homozygotes, and 50 (41%) heterozygotes. We measured HRV indices as described (28). Software (GE Healthcare, Waukesha, WI) was used to identify all normal (NN) cardiac cycles (sequential QRS complexes with normal morphologic characteristics and a cycle duration within 20% of the preceding cycle) and compute time-domain HRV variables, including SDNN.…”

“…The template-directed dye-terminator incorporation assay with fluorescence polarization detection (FP-TDI) (14) was used to determine AKAP10 I646V (rs203462) genotype in 986 participants of the Heart and Soul Study (27,28) who consented to genotyping. …”

“…To test this possibility, we genotyped 122 participants in the Heart and Soul Study (27,28) who had 24-h continuous ECG recording. As predicted, 646V was associated with markers of low vagus nerve sensitivity: fast HR and low HRV.…”