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Elevated resting heart rate was independently associated with a higher rate of advanced adenoma recurrence in a Korean study of colorectal cancer survivors.

While high heart rate is a known predictor of cancer incidence and also of all-cause mortality in cancer patients, Justin Y. Jeon, PhD and colleagues from Yonsei University College of Medicine in Seoul undertook a long-term surveillance study to determine the association between colorectal cancer recurrence and resting heart rate.

In the team had found resting heart rate to be prognostic of mortality in breast cancer patients, also noting a in which a resting heart rate of 75 beats per minute (bpm) or more was an independent mortality predictor in colorectal, pancreatic, and non-small cell lung cancer.

The sample in the current study, published in , consisted of 300 postsurgical patients from a colorectal cancer survivor cohort at Seoul's Severance Hospital. All the patients were assessed 5 years post-treatment for resting heart rate, physical activity, and body composition. Colonoscopy surveillance data were collected for a mean follow-up of 8 years.

Survivors were divided into four groups from lowest to highest resting heart rate:

• quartile 1 -- 45-66 bpm
• quartile 2 -- 67-73 bpm
• quartile 3 -- 74-90 bpm
• quartile 4 -- 81-120 bpm

The mean age across quartiles ranged from 58.5 (who had to highest bpm) to 62.7 (who had the lowest bpm).

The groups did not differ in educational status, alcohol/tobacco use, family history of colorectal cancer, height, weight, body mass index, waist circumference, skeletal muscle mass, or body cell mass. The groups were also comparable in systolic and diastolic blood pressure; tumor location, stage, and grade; medical history; metabolic parameters; and medication use. However, patients in lower bpm quartiles tended to be older and were more often male (64.6%), while more than half of patients in the upper two quartiles were female. The low-bpm patients did more physical activity and had lower levels of body fat mass, percentage of body fat, and visceral fat area, although the difference in the average values was small.

A low heart rate was positively associated with exercise for more than 5 hours or more than 40 MET-hours per week.

A total of 161 patients (54%) were found to have at least one recurrent polyp on colonoscopy, with a mean duration from surgery to recurrence of 45.2 months. In line with previous studies, post-treatment surveillance revealed an adenoma recurrence rate of 32.3% and an advanced adenoma recurrence rate of 9.0%.

Survivors with a high resting heart rate had a significantly higher recurrence rate of advanced adenoma -- but not of tubular adenoma or overall polyps -- than those with a low resting heart rate. The unadjusted rates from the lowest to highest bpm quartile were 3.8%, 7.9%, 10.0%, and 14.7%, respectively (P for trend 0.018).

After adjustment for risk factors, patients in the highest quartile (≥81 bpm) had a significantly higher risk of advanced adenoma recurrence, for a hazard ratio of 6.183 (95% CI 1.181-32.373, P=0.031) compared with those in the lowest quartile (≤66 bpm). For quartile 2, the adjusted recurrence rate was 2.491, and for quartile 3, it was 5.623.

"In subgroup analysis, the association of resting heart rate with advanced adenoma recurrence appeared to be stronger among patients who had more than normal body fat mass or sedentary life style," Jeon and colleagues wrote.

Asked for his perspective, Edward L. Giovannucci, MD, MPH, ScD of Brigham and Women's Hospital and Harvard Medical School in Boston, who was not involved with the study, said that although the study was small and needed replication, it "shows an interesting finding and suggests that heart rate might be a predictor of recurrent adenomas, which may be an indicator of colorectal cancer risk."

He cautioned that while heart rate is a simple measure, the interpretation or significance of heart rate is complex because it has multiple determinants: "For example, aerobic exercise, which induces physical fitness, will lower heart rate. Physical activity and lower body fat are associated with lower risk of colorectal cancer. We don't know the exact reasons, but it might be related to factors like insulin resistance."

Giovanucci also noted that insulin resistance is critical for diabetes and cardiovascular disease risk, and that resting pulse is also predictive of these. "Thus, heart rate is a good marker of many things related to health. How much it adds to clinical prediction of recurrence beyond standard measures is unclear, but worth pursuing."

The mechanisms underlying the heart rate-cancer connection are not well understood but experimental research has suggested a possible molecular pathway in increased activation of the , which might affect inflammation, angiogenesis, tissue invasion, cellular immune response, and epithelial-mesenchymal transition.

Limitations of the study, Jeon et al noted, were its retrospective, cross-sectional, case-control design and its restriction to a single academic hospital. Another drawback was the availability of just one measurement of physical activity, body composition data, and resting heart rate 5 years or more after treatment. Furthermore, the sample size was relatively small, and recurrence was relatively infrequent. "Further studies with larger sample size, longer follow-up, and more events will be needed."

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