Relation of Low Socioeconomic Status to C-Reactive Protein in Patients With Coronary Heart Disease (from the Heart and Soul Study)
2005; Elsevier BV; Volume: 96; Issue: 11 Linguagem: Inglês
10.1016/j.amjcard.2005.07.059
ISSN1879-1913
AutoresLindsey A. Lubbock, Anne Goh, Sadia Ali, James Ritchie, Mary A. Whooley,
Tópico(s)Cardiovascular Health and Risk Factors
ResumoLow socioeconomic status (SES) is associated with poor health outcomes in patients who have coronary heart disease (CHD). Inflammation is a potential mechanism by which low SES may lead to adverse cardiovascular outcomes, but it is not known whether low SES is associated with inflammation in patients who have CHD. We measured high-sensitivity C-reactive protein (CRP) levels in a cross-sectional study of 985 adults who had CHD. Income and education were determined by self-report. We used ordinal logistic regression to examine the association of income and education with CRP. Of the 985 participants, 390 had high CRP levels (>3 mg/dl). The proportion of participants who had high CRP levels ranged from 30% (103 of 340) in those who had a college degree to 51% (65 of 127) in those who had less than a high school degree (p <0.0001). The proportion of subjects who had a high CRP level ranged from 28% (52 of 183) in those who had annual income ≥$50,000 to 42% (199 of 974) in those who had an annual income <$20,000 (p 3 mg/dl). The proportion of participants who had high CRP levels ranged from 30% (103 of 340) in those who had a college degree to 51% (65 of 127) in those who had less than a high school degree (p <0.0001). The proportion of subjects who had a high CRP level ranged from 28% (52 of 183) in those who had annual income ≥$50,000 to 42% (199 of 974) in those who had an annual income <$20,000 (p <0.001). After adjustment for traditional cardiovascular risk factors and other potential confounding variables, lower income and education remained associated with higher CRP levels. In conclusion, low SES is associated with high CRP levels in patients who have CHD. This observation raises the possibility that inflammation may contribute to the adverse cardiovascular outcomes associated with low SES. To determine the relation between socioeconomic status (SES) and level of C-reactive protein (CRP), we assessed income and education and measured CRP in a cross-sectional study of 985 adults who had coronary heart disease (CHD). We hypothesized that lower income and education would be associated with higher CRP levels after adjusting for demographic characteristics, traditional CHD risk factors, medical co-morbidities, medication use, and other clinical indicators. The Heart and Soul Study is a prospective cohort study that examines the influence of psychosocial factors on health outcomes in patients who have coronary artery disease. Methods have been described previously.1Ruo B. Rumsfeld J.S. Hlatky M.A. Liu H. Browner W.S. Whooley M.A. Depressive symptoms and health-related quality of life the Heart and Soul Study.JAMA. 2003; 290: 215-221Crossref PubMed Scopus (652) Google Scholar, 2Beattie M.S. Shlipak M.G. Liu H. Browner W.S. Schiller N.B. Whooley M.A. C-reactive protein and ischemia in users and nonusers of beta-blockers and statins data from the Heart and Soul Study.Circulation. 2003; 107: 245-250Crossref PubMed Scopus (59) Google Scholar Patients who had coronary artery disease were recruited by using administrative databases from 2 Departments of Veterans Affairs Medical Centers (Veterans Affairs Medical Center, San Francisco, and the Veterans Affairs Palo Alto Health Care System, Palo Alto, California), 1 university-based medical center (University of California, San Francisco), and 9 public health clinics in the Community Health Network of San Francisco. Eligibility requirements included a history of any of the following: myocardial infarction, angiographic evidence of ≥50% stenosis in ≥1 coronary vessel, coronary revascularization, a diagnosis of coronary disease that was documented by an internist or cardiologist, or evidence of exercise-induced ischemia by treadmill or nuclear testing. A total of 15,438 eligible patients was mailed an invitation to participate, and 2,495 responded that they would be interested. Of the 2,495 patients whom we attempted to contact by telephone to schedule a study appointment, 505 could not be reached and 596 declined to participate. An additional 370 patients were excluded because they had a history of myocardial infarction in the previous 6 months, deemed themselves unable to walk 1 block, or were planning to move out of the local area within 3 years. Between September 2000 and December 2002, 1,024 participants enrolled and attended a day-long appointment at the Veterans Affairs Medical Center in San Francisco. For this cross-sectional study, we excluded 39 subjects from whom we could not obtain serum samples, leaving 985 participants for analysis. This study protocol was approved by the appropriate institutional review boards, and all participants provided written, informed consent. We evaluated SES by measuring education and income. To assess education, we asked participants, "What is the highest level of education that you have completed?" Multiple-choice responses were grade ≤8, grades 9 to 11, high school graduate or equivalent, some college or vocational school, college degree, or graduate or professional degree. For analysis purposes, we categorized participants as having less than a high school education, a high school diploma, or a college or graduate degree. To determine income, we asked participants, "Which of the following categories best describes your total combined household income for the previous 12 months?" (<$10,000, $10,000 to $19,000, $20,000 to $29,000, $30,000 to $39,999, $40,000 to $50,000, or >$50,000). For analysis purposes, we categorized participants into 1 of 4 income groups (<$20,000, $20,000 to $29,999, $30,000 to $50,000, or ≥$50,000).3Owen N. Poulton T. Hay F.C. Mohamed-Ali V. Steptoe A. Socioeconomic status, CRP, immune factors, and responses to acute mental stress.Brain Behav Immun. 2003; 17: 286-295Crossref PubMed Scopus (159) Google Scholar Participants were instructed to fast for 12 hours (except for medication, which they were to take with water), not to take aspirin for 1 week, and not to smoke for 5 hours. Fasting venous blood samples were obtained, and serum was frozen at −70°C until the time of the CRP assay. We used the Roche Integra high-sensitivity assay (Roche, Indianapolis, Indiana) to measure CRP in 229 participants and (due to a change in the laboratory) the Beckman Extended Range high-sensitivity CRP assay (Beckman, Galway, Ireland) to measure CRP in the remaining 756 participants. We categorized participants by CRP levels 3 mg/L, which corresponded to low, moderate, and high levels of cardiovascular risk, respectively.4Ridker P.M. Inflammation in atherothrombosis how to use high-sensitivity C-reactive protein (hsCRP) in clinical practice.Am Heart Hosp J. 2004; 2: 4-9PubMed Google Scholar The Roche Integra high-sensitivity CRP assay is an immunoturbidimetric assay that uses latex particles that are coated with monoclonal anti-CRP antibody. When the CRP of the sample agglutinates with these particles, a precipitate is formed and the amount is determined turbidimetrically at 522 nm. This assay has been standardized against the World Health Organization reference and compared with the Dade nephelometric method, with a correlation coefficient of 0.997. The interassay coefficient of variation is 3.2%, and the lowest detectable measurement of this assay is 0.025 mg/dl. The Beckman Extended Range CRP assay is also an immunoturbidimetric assay that uses latex particles and a near-infrared particle immunoassay that is measured with a laser diode at 940 nm, with a detection limit of 0.20 mg/L and a measuring range of 0.20 to 1440 mg/L. This assay is highly correlated with the Roche Integra assay (r = 0.99 in a sample of 185 patients). The interassay (between-run) coefficient of variation is ≤6.7%, and the intraassay (within-run) coefficient of variation is <6.2%. Age, gender, ethnicity, smoking, marital status, alcohol use, medical history, angina frequency, and physical activity were determined by a self-report questionnaire. We used the Computerized Diagnostic Interview Schedule, Fourth Edition, to determine the presence of current major depression according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.5Blouin A.G. Perez E.L. Blouin J.H. Computerized administration of the Diagnostic Interview Schedule.Psychiatry Res. 1988; 23: 335-344Abstract Full Text PDF PubMed Scopus (170) Google Scholar, 6Levitan R.D. Blouin A.G. Navarro J.R. Hill J. Validity of the computerized DIS for diagnosing psychiatric inpatients.Can J Psychiatry. 1991; 36: 728-731PubMed Google Scholar Alcohol use was evaluated by using alcohol consumption from the Alcohol Use Disorders Identification Test, with a score ≥4 to define regular alcohol use.7Bush K. Kivlahan D.R. McDonell M.B. Fihn S.D. Bradley K.A. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test.Arch Intern Med. 1998; 158: 1789-1795Crossref PubMed Scopus (4283) Google Scholar Participants were instructed to bring all medication bottles to their study appointment, and the research team recorded all current medications. All participants completed echocardiography at rest for measurement of left ventricular ejection fraction and an exercise treadmill test with stress echocardiography. We calculated the wall motion score index at peak exercise as our measurement of ischemia.8Schiller N.B. Shah P.M. Crawford M. DeMaria A. Devereux R. Feigenbaum H. Gutgesell H. Reichek N. Sahn D. Schnittger I. et al.American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional EchocardiogramsRecommendations for quantitation of the left ventricle by two-dimensional echocardiography.J Am Soc Echocardiogr. 1989; 2: 358-367Abstract Full Text PDF PubMed Scopus (52) Google Scholar Body mass index was calculated as weight in kilograms divided by the square of height in meters. We measured systolic and diastolic blood pressures, fasting total cholesterol level, high-density lipoprotein, low-density lipoprotein, and triglycerides (milligrams per deciliter). Creatinine clearance (milliliter per minute) was calculated from 24-hour urine excretion. This study examined the association of education and income with levels of C-reactive protein. Differences in characteristics of participants by level of CRP ( 3 mg/L) were compared using analysis of variance for continuous variables and chi-square test for dichotomous variables. We used analysis of covariance to compare mean log CRP by categories of income and education. We also compared the unadjusted frequency of low, moderate, and high CRP levels by categories of education and income by using Cochran-Armitage chi-square test for trend. To further evaluate the association between low SES and CRP, we used polytomous (ordinal) logistic regression, with category of income or education as the predictor variable and category of CRP ( 3 mg/L) as the ordinal outcome variable. To obtain adjusted risk estimates, we entered all variables listed in Table 1 into a backward elimination logistic regression models that included different levels of education and income as indicator variables. Variables that were associated with high CRP levels (at p <0.05) were retained in the models. We verified the proportional odds assumption for all models. Results are reported as odds ratios with 95% confidence intervals. Analyses were performed with SAS 8 (SAS Institute, Cary, North Carolina).Table 1Characteristics of 985 participants by level of C-reactive protein (CRP)VariableCRPp Value 3 mg/L (n = 390)Age (yrs)66 ± 1168 ± 1166 ± 110.02Men224 (86%)283 (85%)295 (76%)0.001White151 (58%)208 (62%)236 (61%)0.52Married131 (50%)137 (41%)153 (39%)0.02Current smoking38 (15%)50 (15%)107 (27%)<0.0001Regular alcohol use77 (30%)100 (30%)108 (28%)0.78Hypertension176 (68%)234 (70%)284 (73%)0.36Diabetes mellitus55 (21%)95 (29%)110 (28%)0.07Congestive heart failure33 (13%)53 (16%)87 (22%)0.004Angina weekly or more94 (36%)114 (34%)146 (38%)0.65Previous myocardial infarction136 (52%)188 (57%)203 (52%)0.37Previous stroke34 (13%)49 (15%)55 (14%)0.85Previous coronary artery bypass grafting101 (39%)123 (37%)125 (32%)0.18Previous coronary angioplasty106 (41%)133 (40%)146 (38%)0.67Current depression58 (22%)75 (23%)84 (22%)0.94Not at all or a little physically active63 (24%)112 (34%)185 (48%)<0.0001β-Blocker use160 (61%)191 (57%)214 (55%)0.29Renin-angiotensin system inhibitor use136 (52%)180 (54%)189 (48%)0.31Diuretics (loop or thiazide) use57 (22%)90 (27%)143 (37%)0.0001Statin use177 (68%)230 (69%)226 (58%)0.003Aspirin use216 (82%)257 (77%)288 (74%)0.03Hormone replacement therapy use7 (3%)9 (3%)30 (8%)0.001Ejection fraction (%)0.62 ± 0.090.62 ± 0.100.61 ± 0.100.33Wall motion score index1.14 ± .311.17 ± .341.19 ± .390.22Systolic blood pressure (mm Hg)129 ± 20132 ± 20136 ± 22<0.0001Diastolic blood pressure (mm Hg)73 ± 1275 ± 1176 ± 110.005Total cholesterol (mg/dl)171 ± 37177 ± 43183 ± 460.001High-density lipoprotein (mg/dl)47.8 ± 1546 ± 1444 ± 130.004Low-density lipoprotein (mg/dl)96.5 ± 26104 ± 33110 ± 38<0.0001Creatinine clearance (ml/min)86 ± 2881 ± 2878 ± 290.001Body mass index (kg/m2)27 ± 4.128 ± 530 ± 6<0.0001Triglycerides (mg/dl)136 ± 157137 ± 120147 ± 1130.47Values are means ± SD or numbers of patients (percentages). Open table in a new tab Values are means ± SD or numbers of patients (percentages). Among the 985 study participants, 262 had CRP levels 3 mg/L (Table 1). Compared with participants who had low CRP levels, those who had higher CRP levels were older, less likely to be men or married, and more likely to smoke, to have diabetes, to have congestive heart failure, and to be physically inactive. Participants who had higher CRP levels were also more likely to be taking diuretics, less likely to be taking statins or aspirin, and more likely to be using hormone replacement therapy. They had higher values for blood pressure, low-density lipoprotein, and body mass index and lower values for high-density lipoprotein and creatinine clearance compared with those who had low CRP levels. Mean ± SE log CRP values were 0.48 ± 0.07 mg/dl in the 340 participants who had a college degree, 0.80 ± 0.06 mg/dl in the 516 participants who had a high school degree, and 0.98 ± 0.12 in the 127 participants who had less than a high school degree (p $50,000, 0.75 ± 0.09 in the 189 participants who had an annual income from $30,000 to $50,000, 0.81 ± 0.11 in the 133 participants who had an annual income from $20,000 to $29,999, and 0.82 ± 0.06 in the 474 participants who had an annual income <$20,000 (p = 0.0002). When we divided CRP into categories ( 3 mg/dl), lower income and education levels were associated with higher CRP levels (Figure 1,Table 2). The proportion of participants who had high CRP levels (>3 mg/dl) ranged from 30% in those who had a college degree to 51% in those who had less than a high school education (p <0.0001) and from 28% in those who had an annual income ≥$50,000 to 42% in those who had an annual income <$20,000 (p <0.001). After adjustment for potential confounding variables, lower income and education levels remained associated with higher CRP levels (Table 3).Table 2Socioeconomic status and level of C-reactive protein (CRP) in 985 participants with coronary heart diseaseCRPp Value 3 mg/LEducation Grade ≤81119220.0002 Grades 9–11122043 High school graduate365585 Some college or vocational school85118137 College degree635754 Graduate or professional degree546349 Annual income (United States dollars) <$10,00058871000.002 $10,000–$19,000537799 $20,000–$29,999274561 $30,000–$39,999223140 $40,000–$50,000253338 >$50,000755652Values are numbers of subjects. Open table in a new tab Table 3Association between socioeconomic status and level of C-reactive protein (CRP) ( 3 mg/L)Proportion With CRP >3 mg/LUnadjusted OR (95% CI)p ValueAdjusted OR (95% CI)⁎All variables were entered into a backward elimination ordinal logistic regression model with a p value <0.05 for retention. Other variables associated with high CRP level (at p <0.05) in the education model were white ethnicity, smoker, history of congestive heart failure, not currently depressed, little or no physical activity, not using a β blocker, using hormone therapy, increased systolic blood pressure, high cholesterol level, low high-density lipoprotein level, low creatinine clearance and high body mass index. Other variables associated with high CRP level (at p <0.05) in the income model were white ethnicity, smokers, history of congestive heart failure, not currently depressed, little or not physically activity, not using a β blocker, using hormone therapy, increased systolic blood pressure, low cholesterol level, high low-density lipoprotein level, high triglyceride level, low creatinine clearance, and high body mass index.p ValueAdjusted OR (95% CI)†Further adjusted for other socioeconomic variable (education or income).p ValueEducation ≤11 yrs51% (65/127)2.4 (1.6–3.5)<0.00012.2 (1.4–3.5)0.0012.2 (1.3–3.6)0.002 High school degree43% (222/516)1.7 (1.3–2.2)<0.00011.4 (1.0–1.9)0.031.5 (1.1–2)0.02 College degree or higher30% (103/340)1—1—Annual income <$20,00042% (199/474)2.1 (1.5–2.8)<0.00011.4 (.96–2.1)0.081.2 (0.8–1.9)0.34 $20,000–29,99946% (61/133)2.4 (1.6–3.7)<0.00012.2 (1.4–3.6)0.0012.1 (1.2–3.5)0.006 $30,000–50,00041% (78/189)2.0 (1.3–2.9)0.00051.8 (1.2–2.8)0.0071.7 (1.1–2.7)0.02 ≥$50,00028% (52/183)1—1—1—CI = confidence interval; OR = odds ratio. All variables were entered into a backward elimination ordinal logistic regression model with a p value <0.05 for retention. Other variables associated with high CRP level (at p <0.05) in the education model were white ethnicity, smoker, history of congestive heart failure, not currently depressed, little or no physical activity, not using a β blocker, using hormone therapy, increased systolic blood pressure, high cholesterol level, low high-density lipoprotein level, low creatinine clearance and high body mass index. Other variables associated with high CRP level (at p <0.05) in the income model were white ethnicity, smokers, history of congestive heart failure, not currently depressed, little or not physically activity, not using a β blocker, using hormone therapy, increased systolic blood pressure, low cholesterol level, high low-density lipoprotein level, high triglyceride level, low creatinine clearance, and high body mass index.† Further adjusted for other socioeconomic variable (education or income). Open table in a new tab Values are numbers of subjects. CI = confidence interval; OR = odds ratio. Our cross-sectional study of outpatients who had CHD associated low SES with higher levels of CRP. Associations of lower education and income were independent of each other and persisted after adjustment for traditional cardiovascular risk factors, marital status, and depression. 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Can patient self-management help explain the SES health gradient?.Proc Natl Acad Sci USA. 2002; 99: 10929-10934Crossref PubMed Scopus (349) Google Scholar Whatever the mechanism, our findings suggest that patients who have a low income or education level may benefit from more aggressive management of CHD, including treatment of dyslipidemia, hypertension, diabetes, smoking, obesity, and physical inactivity. Our study has several limitations that should be considered. Income and education were measured by self-report, thus leaving room for inaccuracies in our analysis. Further, our measurement of "overall household income" may not reflect the participants' personal income. However, it is likely a reasonable reflection of participants' SES. Although the 2 CRP assays were highly correlated (r = 0.99), use of 2 different assays still poses a potential limitation. Moreover, stepwise analysis uses a purely statistical method to select significant variables without necessarily considering biologic confounding. In addition, the investigation involved only a minority of female participants, so our results may not generalize to all populations.
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