Unexplained Chest Pain Carries Substantial Cardio Risk

In British primary care, new-onset chest pain often went undiagnosed

The vast majority of British patients who saw their general practitioners for new-onset chest pain received no diagnosis to explain their pain during the following six months, according to a review of more than 170,000 electronic health records.

But these patients suffered cardiovascular events at significantly higher rates at later follow-up -- nearly double at 1 year and more than 20% higher at 5.5 years -- suggesting that patients with unexplained chest pain should be targeted for more aggressive assessment and prevention, according to Kelvin P. Jordan, PhD, of Keele University in England, and colleagues writing online in The BMJ.

At presentation, 72.4% of patients with new-onset chest pain did not have a known cause and 95.2% of these patients did not receive any type of cardiovascular diagnosis during the next six months, the researchers stated.

Patients with unattributed chest pain, including those who underwent cardiac testing, had a higher rate of myocardial infarction during 5.5 years of follow-up, compared to patients whose chest pain was attributed to a non-coronary cause.

"The large group of patients with undiagnosed chest pain in primary care generally do not undergo diagnostic testing but have an increased risk of fatal and non-fatal cardiovascular events for at least five years," the researchers wrote, adding that improvements are needed in the assessment of chest pain in the general practice setting.

They noted that between 1% and 2% of adults in the United Kingdom see their primary care physicians for new-onset chest pain. During this first consultation, GPs may diagnose myocardial infarction, angina, or a non-coronary cause for pain, such as gastroesophageal reflux, anxiety or musculoskeletal disease.

"Most often the GP will record only the symptom at this stage and not attribute it to any specific cause, while pursuing investigations in those for whom coronary heart disease is considered a diagnostic possibility," the researchers wrote.

It has not been clear if patients with unattributed chest pain have a higher risk for cardiovascular events than patients with chest pain attributed to non-coronary causes.

In their newly published study, Jordan and colleagues examined this question by analyzing electronic health records from the CALIBER database in Great Britain, which links primary care, secondary care, coronary registry, and death registry information.

The analysis included 172,180 adult patients presenting with a first episode of recorded chest pain, classified from medical records as diagnosed (non-coronary condition or angina) or undiagnosed (cause unattributed) from 2002 to 2009. None of the patients had a previous diagnosis of cardiovascular disease.

The main study outcomes were fatal and non-fatal cardiovascular events over 5.5 years of follow up, adjusted for age, sex, BMI, smoking status, hypertension and other relevant confounders.

The analysis revealed that:

 â–º A minority of patients in all three groups (non-coronary, 2.0%; unattributed, 11.7%; angina, 31.5%) had a recorded cardiac diagnostic investigation in the first six months after presentation.

 â–ºThe long term incidence of cardiovascular events was higher in those whose chest pain remained unattributed after six months (5,126 of 109,628; 4.7%) compared with patients with an initial diagnosis of non-coronary pain (1,073 of 36,097; 3.0%). Adjusted hazard ratio for 0.5-1 year after presentation was 1.95, 95% CI 1.66-2.31; for one to three years, 1.35, 95% CI 1.23-1.48; for three to 5.5 years: 1.21, 95% CI 1.08-1.37.

 â–º There were more excess myocardial infarctions in the unattributed cause group (214 more than expected based on the rate in the non-coronary group) than in the angina group (132 more than expected).

 â–º Patients who had cardiac diagnostic investigations in the first six months had a higher long-term risk of cardiovascular events, regardless of the initial chest pain label.

Identification of an increased long-term risk for cardiovascular events in patients with unattributed, new-onset chest pain is a new finding, the researchers wrote.

"Implications for clinical practice might include prevention treatment for all patients with unattributed chest pain, even though most will not go on to experience a cardiovascular event," the researchers wrote. "Another option ... would be to target patients with unattributed chest pain for more detailed prognostic characterization to identify those at greater risk more precisely."

But in an editorial published with the study, Tim Holt, PhD, of the University of Oxford, wrote that patients with unattributed chest pain represent "a diverse clinical taxonomy."

"In addition to those whose coronary heart disease may have been missed, people likely to be harmed by excessive investigation may be over-represented in this group, such as those with panic disorder," Holt wrote. "Future research might clarify how we can better assess and meet the individual needs of patients with attributable chest pain."

Funding for this research was provided by PRUGRESS; Medical Research Council Prognosis Research Strategy Partnership; the British Heart Foundation, Cancer Research UK and others.

The researchers declared no relevant relationships with industry related to this study.

Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

• Patients with new onset chest pain which remains undiagnosed and with unattributed cause for six months have higher long-term risk of major cardiovascular events than those with an initial non-coronary diagnosis for their chest pain, according to a British database.
• Note that while new chest pain is a common presentation in primary care, and there are serious consequences if cardiovascular disease is missed, most of these patients do not have a specific diagnosis recorded.