**1. Introduction**

[97] Sherman S, Lehman G. Sphincter of Oddi dysfunction: diagnosis and treatment. JOP.

2001;2:382-400.

134 Dyspepsia - Advances in Understanding and Management

Cardiovascular disease, primarily encompassing coronary heart disease, hypertensive heart disease, heart failure, and stroke, is the number one cause of death globally, with 17.3 million dying from such causes in 2008 and a projected 23.6 million dying from cardiovascular disease in 2030 [1]. Cardiovascular disease affects 1 in every 3 Americans, or an estimated 83.6 million people (myocardial infraction, 7.6 million; angina pectoris, 7.8 million; heart failure, 5.1 million; and stroke of any kind, 6.8 million; high blood pressure, 77.9 million) [2]. Heart disease and stroke results in over 500,000 and 160,000 deaths, respectively, each year in the United States; giving rise to an enormous annual economic burden exceeding \$312 billion in both direct and indirect costs [1,2].

Upper gastrointestinal (or dyspeptic) symptoms, often sub-classified as ulcer-like (localized epigastric pain or nocturnal/fasting pain), gastroesophageal-like (heartburn or regurgitation) or dysmotility-like dyspepsia (postprandial fullness, early satiety, diffuse epigastric pain, belching or abdominal distention) are also highly prevalent worldwide with an average 3 month prevalence rate across an international sample of survey respondents of about 28%, but with higher rates in some countries such as the United States (41.8%) [3] and lower rates in others (Japan's rate=9.4%). Clinically-relevant upper gastrointestinal symptoms have been found to result in high healthcare utilization [4,5]; as noted in one study [4] which found 20% of affected patients visited a physician's office during the 3-months prior to being surveyed, 2% were hospitalized, nearly half used an over-the-counter medication and 27% were prescri‐ bed at least one medication to address their symptoms. Upper gastrointestinal symptoms have

© 2013 Coleman et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

also been associated with significant costs due to lost work productivity [4,5], with those suffering symptoms having an 85% (95% confidence interval, 40%-145%) increased odds of work absenteeism [5], 27% reporting at least one day of reduced or no productivity over a 3 month period, and 89% of this subset of people reported more than one day affected [4]. In addition to these direct and indirect costs, increased intangible costs (pain and suffering) are also an important repercussion of upper gastrointestinal symptoms [6], with these symptoms shown to be associated with significantly impaired wellbeing and patients' ability to perform activities of daily life (subjects reporting relevant upper gastrointestinal symptoms had significantly worse Psychological General Well-Being Index (PGWBI) and Interference with Daily Life Index (IDLI) scores compared with those reporting no or non-relevant symptoms (PGWBI score 65.24 versus 77.91, *p*<0.0001; IDLI score 75.85 versus 98.57, *p<*0.0001). Both cardiovascular disease and upper gastrointestinal symptoms are common diagnoses in daily practice. According to the American Academy of Family Physicians, numerous diagnosis codes for both cardiovascular disease and upper gastrointestinal symptoms are among the most frequently billed for [7].

Beyond both having relatively high frequencies in daily practice and large economic burdens, there are clinical data supporting the hypothesis that upper gastrointestinal symptoms are more prevalent in patients with cardiovascular disease. Previous studies have found upper gastrointestinal symptoms to occur as much as twice as often [8] in patients suffering from a cardiovascular disease [9-13], and moreover, some upper gastrointestinal disorder may

Upper Gastrointestinal Symptoms and Cardiovascular Disease

http://dx.doi.org/10.5772/56564

137

**Figure 1.** Cardiovascular Disease and Upper Gastrointestinal Symptoms on the List of 20 Leading Diagnoses for Direct Healthcare Expenditures (adapted from reference 2) Bars depicts the cost each diagnosis in 2008 US\$, while the labels

The finding of higher prevalence rates of upper gastrointestinal symptoms in patients with cardiovascular disease may exist for a number of reasons. First, there are a host of mutual risk factors for developing both cardiovascular disease and upper gastrointestinal symptoms [18-37]. Next, patients experiencing both health problems often complain of similar or overlapping symptomatology, potentially resulting in the more frequent surveillance and diagnosis of both [38]. Related to this, some studies have suggested that common means of investigating upper gastrointestinal symptom origin can aggravate some cardiovascular diseases or induce cardiovascular symptoms [39,40]. Finally, polypharmacy with drugs used to manage cardiovascular diseases can cause upper gastrointestinal symptoms [8,41-46] resulting in decreased adherence to their medications, and a perhaps initiating a cycle of recurrence/worsening of cardiovascular disease. Moreover, some drugs to treat upper gastrointestinal symptoms may increase cardiovascular disease risk either directly or through

above the bars provides each diagnosis' ranking in direct healthcare expenditures.

drug-drug interactions.

increase patients' risk for cardiovascular disease [14-17].

In addition, cardiovascular and upper gastrointestinal disorders are among the top 20 leading diagnoses for direct health expenditures in the United States [2]. In 2008, approximately \$95.6 billion dollars were spent treating heart conditions and \$27.2 billion were spent treating upper gastrointestinal disorders, making these two disease states the first and twelfth most costly diagnoses, respectively, for direct healthcare expenditures. Since cardiovascular disease and upper gastrointestinal symptoms are both common conditions, some overlap in the occurrence of these conditions would naturally be expected.


**Table 1.** International Classification of Diseases, Ninth Revision, Clinical Modification Codes for Cardiovascular Disease and Upper Gastrointestinal Symptoms Designated in the Top 100 According to the '*Family Practice Management Short List'* [reference 7]

Beyond both having relatively high frequencies in daily practice and large economic burdens, there are clinical data supporting the hypothesis that upper gastrointestinal symptoms are more prevalent in patients with cardiovascular disease. Previous studies have found upper gastrointestinal symptoms to occur as much as twice as often [8] in patients suffering from a cardiovascular disease [9-13], and moreover, some upper gastrointestinal disorder may increase patients' risk for cardiovascular disease [14-17].

also been associated with significant costs due to lost work productivity [4,5], with those suffering symptoms having an 85% (95% confidence interval, 40%-145%) increased odds of work absenteeism [5], 27% reporting at least one day of reduced or no productivity over a 3 month period, and 89% of this subset of people reported more than one day affected [4]. In addition to these direct and indirect costs, increased intangible costs (pain and suffering) are also an important repercussion of upper gastrointestinal symptoms [6], with these symptoms shown to be associated with significantly impaired wellbeing and patients' ability to perform activities of daily life (subjects reporting relevant upper gastrointestinal symptoms had significantly worse Psychological General Well-Being Index (PGWBI) and Interference with Daily Life Index (IDLI) scores compared with those reporting no or non-relevant symptoms (PGWBI score 65.24 versus 77.91, *p*<0.0001; IDLI score 75.85 versus 98.57, *p<*0.0001). Both cardiovascular disease and upper gastrointestinal symptoms are common diagnoses in daily practice. According to the American Academy of Family Physicians, numerous diagnosis codes for both cardiovascular disease and upper gastrointestinal symptoms are among the

In addition, cardiovascular and upper gastrointestinal disorders are among the top 20 leading diagnoses for direct health expenditures in the United States [2]. In 2008, approximately \$95.6 billion dollars were spent treating heart conditions and \$27.2 billion were spent treating upper gastrointestinal disorders, making these two disease states the first and twelfth most costly diagnoses, respectively, for direct healthcare expenditures. Since cardiovascular disease and upper gastrointestinal symptoms are both common conditions, some overlap in the occurrence

Atrial fibrillation 427.31 Chronic ischemic heart disease, unspec. 414.9 Heart failure, congestive, unspec. 428.0 Hypertension, benign 401.1 Hypertension, unspecified 401.9 Chest pain, unspec. 786.50

Gastroenteritis, noninfectious, unspec. 558.9 Gastroesophageal reflux, no esophagitis 530.81 Nausea w/ vomiting 787.01

**Table 1.** International Classification of Diseases, Ninth Revision, Clinical Modification Codes for Cardiovascular Disease and Upper Gastrointestinal Symptoms Designated in the Top 100 According to the '*Family Practice Management Short*

**Diagnosis description Diagnosis code (ICD-9-CM)**

most frequently billed for [7].

136 Dyspepsia - Advances in Understanding and Management

*Cardiovascular disease*

*Upper gastrointestinal symptoms*

*List'* [reference 7]

of these conditions would naturally be expected.

**Figure 1.** Cardiovascular Disease and Upper Gastrointestinal Symptoms on the List of 20 Leading Diagnoses for Direct Healthcare Expenditures (adapted from reference 2) Bars depicts the cost each diagnosis in 2008 US\$, while the labels above the bars provides each diagnosis' ranking in direct healthcare expenditures.

The finding of higher prevalence rates of upper gastrointestinal symptoms in patients with cardiovascular disease may exist for a number of reasons. First, there are a host of mutual risk factors for developing both cardiovascular disease and upper gastrointestinal symptoms [18-37]. Next, patients experiencing both health problems often complain of similar or overlapping symptomatology, potentially resulting in the more frequent surveillance and diagnosis of both [38]. Related to this, some studies have suggested that common means of investigating upper gastrointestinal symptom origin can aggravate some cardiovascular diseases or induce cardiovascular symptoms [39,40]. Finally, polypharmacy with drugs used to manage cardiovascular diseases can cause upper gastrointestinal symptoms [8,41-46] resulting in decreased adherence to their medications, and a perhaps initiating a cycle of recurrence/worsening of cardiovascular disease. Moreover, some drugs to treat upper gastrointestinal symptoms may increase cardiovascular disease risk either directly or through drug-drug interactions.

The aim of this chapter is to provide a detailed discussion of the evidence suggesting and supporting an increased risk of upper gastrointestinal symptoms in populations suffering from cardiovascular disease.

**Study, year (N=)**

Lohr 1986 (N=4,962)

LaMori 2012 (N=1,297)

Laliberte 2012 (N=413,168)

Pasini 1989 (N=NR)

**Study Description Key Finding**

Higher odds of having first time diagnosis of chest pain (OR=2.3, 95%CI=2.0-2.8) or angina (OR=2.7, 95%CI=1.8-4.0) in dyspepsia group in the year after

Upper Gastrointestinal Symptoms and Cardiovascular Disease

http://dx.doi.org/10.5772/56564

139

Congestive heart failure and angina were associated with a 3.6-fold (p<0.001) and 2.9-fold (p<0.05)

Dyspepsia more likely among patients with higher

Patients reporting dyspepsia in addition to AF had higher mean CHADS2 scores (1.9 vs. 1.4, p<0.05)

Incidence rate of dyspepsia was found to be 14.7 per

Data showed alterations of motility in esophagus, stomach, duodenum in every patient and lesions of gastric mucous membrane in more than half

index date than in control cohort

higher odds of ulcer-like symptoms

stroke risk (CHADS2 ≥2, OR=1.15)

100-patients years

AF=atrial fibrillation; FD=Functional dyspepsia; HLD=hyperlipidemia; HTN=hypertension; NA=not applicable; NR=not reported; OR=odds ratio; UK=United Kingdom; UGIS=upper gastrointestinal symptoms; USA=United States of America

A second study, the large Domestic/International Gastroenterology Surveillance Study [8] looked to investigate any association between upper gastrointestinal symptoms (gastroeso‐ phageal-, ulcer- or dysmotility-like) and lifestyle factors (including comorbidities) in a large sample of patients experiencing dyspepsia in the prior 3-months. A sample of urban, adult populations from seven geographic areas (Canada, United States, Switzerland, the Nether‐ lands, Italy, Japan and the Nordic countries) was obtained by door-to-door or telephone recruitment. Subjects were divided into groups depending on whether gastrointestinal

**Table 2.** Studies Assessing Upper Gastrointestinal Symptoms in Patients with Cardiovascular Disease

(95%CI 15.0-15.6) per 1000 person-years

Respondents completing a questionnaire enrolled in the Rand Health Insurance Experiment from six sites (Dayton, Ohio; Seattle, Washington; Fitchburg, Massachusetts; Franklin County,

Massachusetts; Charleston, South Carolina; and Georgetown County, South Carolina); prevalence rate of ulcer-like symptoms per 100 (aged 18-61 years) men=3.8 and

Respondents to the 2009 National Health and Wellness Survey, a nationwide (USA) selfadministered internet-based questionnaire;

Retrospective database study of Thomson Reuters MarketScan data from 2005 and 2009 to quantify the incidence of dyspeptic events in patients with atrial fibrillation;

Italian patients affected with congestive heart failure and ischemic heart disease studied to ascertain relation between dyspeptic syndrome and acute cardiac

prevalence rate of dyspepsia=34%

median follow-up of 563 days

(n=6,913)

women=3.8

disorders
