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Caregiving and risk of coronary heart disease in U.S. women

A prospective study
  • Sunmin Lee
    Affiliations
    Department of Health and Social Behavior (Lee, Berkman, Kawachi), Harvard School of Public Health, Boston, Massachusetts, USA

    Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School (Lee, Colditz, Kawachi), Boston, Massachusetts, USA
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  • Graham A Colditz
    Affiliations
    Department of Epidemiology (Colditz), Harvard School of Public Health, Boston, Massachusetts, USA

    Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School (Lee, Colditz, Kawachi), Boston, Massachusetts, USA

    Harvard Center for Cancer Prevention (Colditz), Boston, Massachusetts, USA
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  • Lisa F Berkman
    Affiliations
    Department of Health and Social Behavior (Lee, Berkman, Kawachi), Harvard School of Public Health, Boston, Massachusetts, USA

    Harvard Center for Society and Health (Berkman, Kawachi), Boston, Massachusetts, USA
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  • Ichiro Kawachi
    Correspondence
    Address correspondence and reprint requests to: Ichiro Kawachi, MD, PhD, Department of Health and Social Behavior, Harvard School of Public Health, 677 Huntington Avenue, Boston MA 02115,USA.
    Affiliations
    Department of Health and Social Behavior (Lee, Berkman, Kawachi), Harvard School of Public Health, Boston, Massachusetts, USA

    Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School (Lee, Colditz, Kawachi), Boston, Massachusetts, USA

    Harvard Center for Society and Health (Berkman, Kawachi), Boston, Massachusetts, USA
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      Abstract

      Background

      A growing number of women provide care to disabled or ill relatives. Many studies have linked caregiving to psychiatric morbidity, lower perceived health status, elevated blood pressure, and poorer immune function. However, no studies have examined the association between caregiving and cardiovascular disease incidence.

      Methods

      We conducted the study in 54,412 women from the Nurses’ Health Study, a prospective cohort of female registered nurses residing in 11 U.S. states. These women were aged 46 to 71 years and did not have diagnosed coronary heart disease (CHD), stroke, or cancer at baseline (1992). We collected information on caregiving responsibilities in 1992 and coronary heart disease between baseline (June 1, 1992) and return of the 1996 questionnaire.

      Results

      During 4 years of follow-up, we documented 321 incident cases of CHD (231 nonfatal cases of myocardial infarction and 90 CHD deaths). In multivariate analyses controlling for age, smoking, exercise, alcohol intake, body mass index, history of hypertension, diabetes mellitus, and other covariates, caregiving for disabled or ill spouse for ≥9 hours per week was associated with increased risk of CHD (RR, 1.82; 95% confidence interval, 1.08–3.05). However, caregiving for disabled or ill parents or disabled or ill others was not significantly associated with increased risks of CHD.

      Conclusion

      These data indicate that high levels of caregiving burden for ill spouses may increase the risk of CHD among women.

      Introduction

      More than 25 million family caregivers provide informal care to disabled or ill family members in the United States.

      Levine C. Always on call. New York: United Hospital Fund, 2000

      More than half of American women will care for a sick or disabled family member at some point during their adult lives.
      • Moen P.
      • Robinson J.
      • Dempster-McClain D.
      Caregiving and women’s well-being a life course approach.
      The economic value of informal care is estimated at $196 billion (in 1997 dollars), which is equivalent to 18% of the total national healthcare expenditure.
      • Arno P.
      • Levine C.
      • Memmott M.
      The economic value of informal caregiving.
      Caregiving is “women’s work.” One survey reported that women are twice as likely to care for someone for ≥20 hours a week and are 1.5 times as likely as men to perform more labor-intensive or intimate care tasks.

      Levine C et al. A survey of family caregivers in New York City: findings and implications for the health care system. New York: United Hospital Fund, 2000

      Although many caregivers describe their work in rewarding terms, an increasing number of studies have begun to suggest health risks. Caregiving has been linked to psychiatric morbidity such as clinical depression and anxiety,
      • Schulz R.
      • Visintainer P.
      • Silliamson G.M.
      Psychiatric and physical morbidity effects of caregiving.
      ,
      • Schulz R.
      • O’Brien A.
      • Bookwala J.
      • Fleissner K.
      Psychiatric and physical morbidity effects of dementia caregiving prevalence, correlates, and causes.
      lower perceived health status, elevated blood pressure,
      • Moritz D.
      • Kasl S.
      • Ostfeld A.
      The health impact of living with a cognitively impaired elderly spouse.
      ,
      • King A.
      • Oka R.
      • Young D.
      Ambulatory blood pressure and heart rate responses to the stress of work and caregiving in older women.
      and greater cardiovascular reactivity.
      • Vitaliano P.
      • Russo J.
      • Bailey S.
      • Young H.
      • McCann B.
      Psychosocial factors associated with cardiovascular reactivity in older adults.
      Some researchers found that caregivers have poorer immune function than controls
      • Glaser R.
      • Kiecolt-Glaser J.
      Chronic stress modulates the virus-specific immune response to latent herpes simplex virus type 1.
      ,
      • Kiecolt-Glaser J.
      • Glaser R.
      • Gravenstein S.
      • Malarkey W.
      • Sheridan J.
      Chronic stress alters the immune response to influenza virus vaccine in older adults.
      ,
      • Kiecolt-Glaser J.
      • Dura J.
      • Speicher C.
      • Trask O.
      • Glaser R.
      Spousal caregivers of dementia victims longitudinal changes in immunity and health.
      and are slower at wound healing.
      • Kiecolt-Glaser J.
      • Marucha P.
      • Malarkey W.
      • Mercado A.
      • Glaser R.
      Slowing of wound healing by psychological stress.
      More recent evidence points to serious long-term consequences of caregiving. Schulz and Beach
      • Schulz R.
      • Beach S.B.
      Caregiving as a risk factor for mortality.
      found caregivers who experienced caregiver strain had an increased risk of mortality compared to noncaregiving controls (relative risk=1.63). However, limited statistical power precluded analysis of cause-specific mortality in that study.
      Given the previously reported associations between caregiving burdens and high blood pressure as well as cardiovascular reactivity, we sought to examine whether caregiving was associated with cardiovascular disease incidence. In the present study, we examined prospectively the association between caregiving responsibilities (for disabled or ill spouse, disabled or ill parent, and disabled or ill others) and incidence of coronary heart disease (CHD) in a cohort of middle-aged and older women.

      Methods

      Study population

      Study subjects were drawn from the Nurses’ Health Study, an ongoing cohort of U.S. female registered nurses. The Nurses’ Health Study was established in 1976 when 121,700 female registered nurses, aged 30 to 55 years, completed a mailed questionnaire providing information about risk factors for cardiovascular disease, cancer, and other major health conditions. Since then, follow-up questionnaires have been mailed to the cohort every 2 years to update information on exposures and the occurrence of major illnesses.

      Assessment of caregiving

      On the 1992 questionnaire, participants self-reported the number of hours per week they typically spent providing care to family members. The question asked: “Outside of your employment, do you provide regular care to any of the following? Disabled or ill spouse, disabled or ill parent, disabled or ill others, non-ill children, and non-ill grandchildren.” In the present study, we focused on caregiving to disabled or ill spouse, disabled or ill parent, and disabled or ill others. Participants could respond that they cared for each person zero (0) hours per week (reference category), 1–8, 9–20, 21–35, 36–72, or ≥73 hours per week. Weekly totals were reported separately for each type of care.
      We also asked caregivers to rate the degree of stress and reward associated with providing care: “How stressful would you say it is to provide care to the individuals mentioned above?” and “How rewarding would you say it is to provide care to the individuals mentioned above?” These questions were asked in a way that it did not specify care recipients. Thus, stress and reward responses were based on caregiving experience from any of the three caregiving groups (disabled or ill spouse, parents, and others). For both questions, the possible responses included: not applicable; not at all; just a little bit; moderately; extremely; don’t know. Participants who answered “don’t know” (n=1740 [1.6%] for stress question; n=2967 [2.8%] for reward question) were excluded from analyses of these items.

      Ascertainment of CHD

      The endpoint for this study comprised incident cases of nonfatal myocardial infarction (MI) and fatal CHD that occurred after the return of the 1992 questionnaire but before June 1, 1996. Each woman who reported having nonfatal MI was asked for permission to review her medical records. Cases were confirmed if they met the diagnostic criteria of the World Health Organization (i.e., symptoms plus either cardiac enzyme level elevations or diagnostic ECG changes).

      Rose G, Blackburn H. Cardiovascular survey methods. 2nd ed. Geneva: World Health Organization, 1982

      Physicians reviewed medical records that were blinded to exposure status. An MI was defined as probable if medical records were not available but hospitalization occurred, and confirmatory information was obtained by interview or letter. The present analyses included both definite and probable cases. Of the CHD cases, 92% included herein were “definite” by these criteria.
      Next of kin or postal authorities reported most deaths. The ascertainment of death also included systematic searches of the state vital records and the National Death Index to identify deaths among participants who did not respond during each questionnaire cycle. More than 98% of deaths in the cohort are estimated to have been identified by this method.
      • Stampfer M.
      • Willett W.
      • Speizer F.
      • Dysert D.
      • Lipnick R.
      • Rosner B.
      Test of the National Death Index.
      If death appeared to be from vascular causes, written permission was requested from the next of kin (subject to the regulations of vital records offices) to review medical records. Fatal CHD was defined as fatal MI confirmed by hospital records or at autopsy or as CHD recorded on the death certificate, if this was the underlying and most probable cause given and there was previous evidence of CHD. In no instance was the cause on the death certificate accepted without corroboration. Total CHD was defined as nonfatal MI plus fatal CHD.

      Exclusions

      Of the 121,700 women in the cohort in 1976, we excluded participants who had died prior to 1992 (n=2888) or who had a history of CHD (n=7728), stroke (n=1087), or cancer (n=13,068). Therefore, the study population was free of diagnosed CHD, stroke, and cancer (except nonmelanoma skin cancer) at the beginning of follow-up. An additional 11,322 women (9.3% of the cohort) were excluded due to not returning the 1992 questionnaire. We further excluded 29,607 women in whom information on caregiving was missing even though they responded to the 1992 questionnaire. Questions related to caregiving were asked on the last page of the 1992 questionnaire, which was mailed only once to the cohort. Although a shortened version of the 1992 questionnaire was mailed up to four times to nonrespondents (resulting in an over 90% eventual response rate), the caregiving items were dropped from the repeat mailings in order to reduce respondent burden and to maximize the response rate. The response rate to the single mailing of the long version of the 1992 questionnaire (which included the caregiving items) was 65%. In addition to the exclusions outlined above, 1589 women were excluded due to loss of follow-up or nonresponse during follow-up in 1994 and 1996. Our final study population therefore comprised 54,411 women. Women who were excluded because of missing information on caregiving or nonresponse during follow-up (n=40,929) had a higher current smoking rate (21.7% vs. 13.9%), and lower rate of current postmenopausal hormone use (22.3% vs. 35.2%) than our study population (i.e., women who provided complete information on caregiving in 1992). They were also more likely to be currently married (91.6% vs. 82.5%) and have lower level of education (12.7% vs 30.6% college level or higher). We controlled for these and other cardiovascular risk factor in our analyses.

      Covariates

      Relative risks (RRs) were adjusted for age categorized in 5-year groups, and 95% confidence intervals (CIs) were calculated. Proportional hazards models were used to adjust for multiple risk factors, including smoking (never, past, current 1 to 14 cigarettes/day, current 15 to 24 cigarettes/day, current ≥25 cigarettes/day); alcohol intake (0; 0.1 to 4.9 grams/day [one-third to one-half drink per day]; 5.0 to 14.9 grams/day [about one drink]; or ≥15.0 grams/day [more than one drink per day], with one drink considered as the size of a can of beer [12.8 grams], a glass of wine [11.0 grams], or a standard drink of spirits [14.0 grams]); body mass index (BMI; kg/m2 in quintiles); history of hypertension, diabetes mellitus, and hypercholesterolemia; menopausal status (yes/no); current use of postmenopausal hormones; average aspirin use (<1, 1 to 6, and ≥7 tablets/week); past use of oral contraceptives; quintiles of saturated fat intake; quintiles of vitamin E intake; and quintiles of physical activity. Recreational physical activity was assessed from the responses to questions about the frequency of engagement in eight common activities. Each activity was converted to metabolic equivalent hours (MET-hours) per week. One MET-hour is equivalent to the energy expenditure during 1 hour of rest. For example, walking at an average pace for 1 hour is estimated to consume about 3.0 MET units, while jogging or bicycling is estimated to consume about 7.0 MET units. In this analysis, physical activity was divided into quintiles based on MET units. We also adjusted for parental history of MI before age 60 years; educational attainment (registered nurse, bachelor’s degree, graduate degree); marital status (currently married, divorced, widowed); and husband’s educational attainment (high school graduate, bachelor’s degree, graduate degree, missing information).

      Data analyses

      The major focus of the data analyses was the prospective relationship between caregiving hours and incidence of CHD. Information on potential confounders (e.g., personal history of hypertension, hypercholesterolemia, diabetes, physical activity, smoking, cholesterol intake, and postmenopausal hormone use) was ascertained in 1992 and updated in 1994 according to the information provided by the participants on the biennial questionnaire. An example of how we treated these time-varying covariates follows: If a woman smoked in 1992 but stopped in 1994, and then developed a heart attack in 1995, she would have contributed 2 years of person-time as a smoker and 1 year of person-time as a former smoker.
      In all models, caregiving measures were treated as categorical variables. On the basis of the distribution of caregiving hours, we combined some of the higher categories. Relative risks for any one type of caregiving were adjusted for all other types of caregiving. For example, when examining the effect of caregiving for an ill spouse, we controlled for caregiving for ill parents and ill others.
      Stress and reward measures were also treated as categorical variables. Among the five possible responses (not applicable [no caregiving], not at all stressful/rewarding, just a little bit, moderately, and extremely), we combined “not at all” with “just a little bit,” and “moderately” with “extremely.” Then we compared each group with women providing no care.
      The RR was defined as the CHD incidence rate among those who provided care divided by the corresponding rate among women who did not provide care. In multivariate analyses, possible confounders listed under the Covariates section were adjusted. All analyses were performed using SAS (SAS Institute Inc., Cary, North Carolina).

      Results

      Table 1 shows the age-standardized distribution of risk factors for CHD and other characteristics according to type of care provided. Women in the “No care” category were individuals reporting no caregiving responsibilities. Women providing care to an ill/disabled spouse were more likely to report a personal history of hypertension, diabetes mellitus, and hypercholesterolemia compared to those not providing care at all or providing care to other types of relatives. They were also slightly more likely to smoke, consumed more saturated fat, and had higher BMI scores. Their husband’s education was lower compared with noncaregivers or other types of caregivers. Women who provided care to ill parents were younger than those who provided care to an ill spouse, ill others, or who provided no care. The proportions of women reporting current use of postmenopausal hormones and past use of oral contraceptives were slightly higher in those who provided no care. Alcohol intake was also slightly higher in women who provided no care. These differences in risk factors for CHD were controlled in examining the association of caregiving and risk of CHD.
      Table 1Mean ages and age-standardized distribution of risk factors for CHD and other characteristics according to types of caregiving
      CharacteristicsNo careIll spouseIll parentIll others
      N25,985236965844399
      Mean age (years)59.360.756.159.0
      Hypertension (%)30.533.629.832.3
      Diabetes mellitus (%)4.25.94.44.9
      Hypercholesterolemia (%)43.145.843.144.4
      Smoking (%)
      Never42.545.247.848.0
      Past43.539.638.737.7
      Current14.015.213.614.3
      Current use of postmenopausal hormones (%)37.134.335.133.8
      Past use of oral contraceptives (%)52.449.150.249.2
      Parental history of MI before age 60 years (%)13.114.911.913.3
      Alcohol intake (g/d)5.84.44.74.8
      Highest quintile of exercise >40 MET hours %20.219.619.522.0
      Highest quintile of vitamin E intake (%)19.218.918.618.6
      Highest quintile of saturated fat intake (%)17.721.019.017.7
      Mean body mass index (kg/m2)25.627.026.126.1
      Aspirin use ≥7 tablets/week (%)15.317.515.516.7
      Marital status (%)
      Currently married80.997.386.878.9
      Divorced or separated8.81.27.09.0
      Widowed10.31.46.212.2
      Education (%)
      Registered nurse68.472.168.071.2
      Bachelor’s degree20.318.721.720.7
      Graduate degree11.39.210.38.1
      Employment status (%)
      Full-time nurse53.251.152.544.3
      Part-time nurse27.231.631.237.5
      Full-time other10.57.68.27.6
      Part-time other9.19.88.210.6
      Husband education (%)
      High school graduate37.150.338.939.3
      Bachelor’s degree25.222.626.124.4
      Graduate degree21.618.021.219.7
      Missing16.19.113.816.6
      CHD, coronary heart disease; MET, metabolic equivalents; MI, myocardial infarction.

      Caregiving to disabled or ill spouse or relatives

      In total, 321 incident cases of CHD (including 231 nonfatal MI and 90 CHD deaths) occurred during 4 years of follow-up. The age-adjusted RR of total incident CHD was 1.93 (95% CI, 1.16–3.20) in women of providing care ≥9 hours per week to a disabled or ill spouse compared with women with no caregiving responsibilities (Table 2). Multivariate RR remained elevated when we controlled for a range of risk factors for CHD (RR=1.82, 95% CI, 1.08–3.05).
      Table 2Relative risk of CHD among caregivers of disabled or ill spouse
      0 hours/week1 to 8 hours/week (95% CI)≥9 hours/week (95% CI)
      Total CHD
      Cases297816
      Age-adjusted RR1.001.06 (0.52–2.14)1.93 (1.16–3.20)
      Multivariate RR
      Adjusted for age in 5-year intervals; follow-up period (1992–1994, 1994–1996); smoking (never, past, current 1–14, current 14–25, current >25 cigarettes/day); alcohol intake (0, 0.1–4.9 g/day, 5.0–14.9 g/day, ≥5.0 g/day); body mass index (in quintiles); history of hypertension, diabetes mellitus, and hypercholesterolemia; menopausal status; current use of postmenopausal hormones; average aspirin use (<1, 1–6, and ≥7 tablets/week); past use of oral contraceptives; quintiles of saturated fat intake; quintiles of vitamin E intake; quintiles of physical activity; parental history of myocardial infarction before age 60 years; educational attainment (registered nurse, bachelors degree, graduate degree); marital status (currently married, divorced, widowed); husbands educational attainment (high school graduate, bachelors degree, graduate degree, missing information).
      1.001.11 (0.54–2.25)1.82 (1.08–3.05)
      Nonfatal CHD
      Cases214710
      Age-adjusted RR1.001.28 (0.60–2.73)1.66 (0.87–3.13)
      Multivariate RR
      Adjusted for age in 5-year intervals; follow-up period (1992–1994, 1994–1996); smoking (never, past, current 1–14, current 14–25, current >25 cigarettes/day); alcohol intake (0, 0.1–4.9 g/day, 5.0–14.9 g/day, ≥5.0 g/day); body mass index (in quintiles); history of hypertension, diabetes mellitus, and hypercholesterolemia; menopausal status; current use of postmenopausal hormones; average aspirin use (<1, 1–6, and ≥7 tablets/week); past use of oral contraceptives; quintiles of saturated fat intake; quintiles of vitamin E intake; quintiles of physical activity; parental history of myocardial infarction before age 60 years; educational attainment (registered nurse, bachelors degree, graduate degree); marital status (currently married, divorced, widowed); husbands educational attainment (high school graduate, bachelors degree, graduate degree, missing information).
      1.001.35 (0.63–2.90)1.55 (0.81–2.96)
      Fatal CHD
      There were too few cases of fatal CHD to carry out multivariate analyses.
      Cases8316
      Age-adjusted RR1.000.48 (0.07–3.45)2.64 (1.15–6.08)
      CHD, coronary heart disease; CI, confidence interval; RR, relative risk.
      a Adjusted for age in 5-year intervals; follow-up period (1992–1994, 1994–1996); smoking (never, past, current 1–14, current 14–25, current >25 cigarettes/day); alcohol intake (0, 0.1–4.9 g/day, 5.0–14.9 g/day, ≥5.0 g/day); body mass index (in quintiles); history of hypertension, diabetes mellitus, and hypercholesterolemia; menopausal status; current use of postmenopausal hormones; average aspirin use (<1, 1–6, and ≥7 tablets/week); past use of oral contraceptives; quintiles of saturated fat intake; quintiles of vitamin E intake; quintiles of physical activity; parental history of myocardial infarction before age 60 years; educational attainment (registered nurse, bachelors degree, graduate degree); marital status (currently married, divorced, widowed); husbands educational attainment (high school graduate, bachelors degree, graduate degree, missing information).
      b There were too few cases of fatal CHD to carry out multivariate analyses.
      We found no evidence of increased CHD risk among women providing care to disabled or ill parent and disabled or ill others compared to women with no caregiving responsibilities (Table 3). We checked to see if number of siblings among caregivers of ill parents made any difference to risk of CHD, assuming that women with no siblings have a higher burden of caregiving to parents. Among parent caregivers, women with no siblings had increased risk of CHD (RR=3.01; 95% CI, 0.88–10.29) compared with women with siblings, although the estimate is based on 11 cases and the CI is wide.
      Table 3Relative risk of CHD among caregivers of disabled or ill parent and disabled or ill others
      Type of care0 hours/week1–8 hours/week (95% CI)≥9 hours/week (95% CI)
      Ill parent
      Total CHD
      Cases2941710
      Age-adjusted RR1.000.74 (0.45–1.22)0.92 (0.49–1.74)
      Multivariate RR
      Adjusted for age in 5-year intervals; follow-up period (1992–1994, 1994–1996); smoking (never, past, current 1–14, current 14–25, current >25 cigarettes/day); alcohol intake (0, 0.1–4.9 g/day, 5.0–14.9 g/day, ≥15.0 g/day); body mass index (in quintiles); history of hypertension, diabetes mellitus, and hypercholesterolemia; menopausal status; current use of postmenopausal hormones; average aspirin use (<1, 1–6, and ≥7 tablets/week); past use of oral contraceptives; quintiles of saturated fat intake; quintiles of vitamin E intake; quintiles of physical activity; parental history of myocardial infarction before age 60 years; educational attainment (registered nurse, bachelors degree, graduate degree); marital status (currently married, divorced, widowed); husbands educational attainment (high school graduate, bachelors degree, graduate degree, missing information).
      1.000.83 (0.50–1.36)0.81 (0.43–1.53)
      Nonfatal CHD
      Cases211119
      Age-adjusted RR1.000.68 (0.37–1.24)1.16 (0.60–2.27)
      Multivariate RR
      Adjusted for age in 5-year intervals; follow-up period (1992–1994, 1994–1996); smoking (never, past, current 1–14, current 14–25, current >25 cigarettes/day); alcohol intake (0, 0.1–4.9 g/day, 5.0–14.9 g/day, ≥15.0 g/day); body mass index (in quintiles); history of hypertension, diabetes mellitus, and hypercholesterolemia; menopausal status; current use of postmenopausal hormones; average aspirin use (<1, 1–6, and ≥7 tablets/week); past use of oral contraceptives; quintiles of saturated fat intake; quintiles of vitamin E intake; quintiles of physical activity; parental history of myocardial infarction before age 60 years; educational attainment (registered nurse, bachelors degree, graduate degree); marital status (currently married, divorced, widowed); husbands educational attainment (high school graduate, bachelors degree, graduate degree, missing information).
      1.000.75 (0.41–1.40)1.03 (0.53–2.03)
      Fatal CHD
      There were too few cases of fatal CHD to carry out multivariate analyses.
      Cases8361
      Age-adjusted RR1.000.90 (0.39–2.08)0.32 (0.05–2.32)
      Ill others
      Total CHD
      Cases300156
      Age-adjusted RR1.000.67 (0.40–1.12)1.11 (0.49–2.49)
      Multivariate RR
      Adjusted for age in 5-year intervals; follow-up period (1992–1994, 1994–1996); smoking (never, past, current 1–14, current 14–25, current >25 cigarettes/day); alcohol intake (0, 0.1–4.9 g/day, 5.0–14.9 g/day, ≥15.0 g/day); body mass index (in quintiles); history of hypertension, diabetes mellitus, and hypercholesterolemia; menopausal status; current use of postmenopausal hormones; average aspirin use (<1, 1–6, and ≥7 tablets/week); past use of oral contraceptives; quintiles of saturated fat intake; quintiles of vitamin E intake; quintiles of physical activity; parental history of myocardial infarction before age 60 years; educational attainment (registered nurse, bachelors degree, graduate degree); marital status (currently married, divorced, widowed); husbands educational attainment (high school graduate, bachelors degree, graduate degree, missing information).
      1.000.65 (0.39–1.10)0.83 (0.36–1.87)
      Nonfatal CHD
      Cases217113
      Age-adjusted RR1.000.67 (0.37–1.24)0.76 (0.24–2.39)
      Multivariate RR
      Adjusted for age in 5-year intervals; follow-up period (1992–1994, 1994–1996); smoking (never, past, current 1–14, current 14–25, current >25 cigarettes/day); alcohol intake (0, 0.1–4.9 g/day, 5.0–14.9 g/day, ≥15.0 g/day); body mass index (in quintiles); history of hypertension, diabetes mellitus, and hypercholesterolemia; menopausal status; current use of postmenopausal hormones; average aspirin use (<1, 1–6, and ≥7 tablets/week); past use of oral contraceptives; quintiles of saturated fat intake; quintiles of vitamin E intake; quintiles of physical activity; parental history of myocardial infarction before age 60 years; educational attainment (registered nurse, bachelors degree, graduate degree); marital status (currently married, divorced, widowed); husbands educational attainment (high school graduate, bachelors degree, graduate degree, missing information).
      1.000.66 (0.36–1.22)0.56 (0.18–1.77)
      Fatal CHD
      There were too few cases of fatal CHD to carry out multivariate analyses.
      Cases8343
      Age-adjusted RR1.000.65 (0.24–1.77)2.01 (0.63–6.35)
      CHD, coronary heart disease; CI, confidence interval; RR, relative risk.
      a Adjusted for age in 5-year intervals; follow-up period (1992–1994, 1994–1996); smoking (never, past, current 1–14, current 14–25, current >25 cigarettes/day); alcohol intake (0, 0.1–4.9 g/day, 5.0–14.9 g/day, ≥15.0 g/day); body mass index (in quintiles); history of hypertension, diabetes mellitus, and hypercholesterolemia; menopausal status; current use of postmenopausal hormones; average aspirin use (<1, 1–6, and ≥7 tablets/week); past use of oral contraceptives; quintiles of saturated fat intake; quintiles of vitamin E intake; quintiles of physical activity; parental history of myocardial infarction before age 60 years; educational attainment (registered nurse, bachelors degree, graduate degree); marital status (currently married, divorced, widowed); husbands educational attainment (high school graduate, bachelors degree, graduate degree, missing information).
      b There were too few cases of fatal CHD to carry out multivariate analyses.
      Results were very similar when the coronary endpoints were confined to definite cases of CHD (N=303) in all three categories of caregiving.

      Caregiving stress and reward

      Neither caregiving stress nor reward was associated with incidence of CHD for any category of caregiving (Table 4). The multivariate RR of total CHD in women reporting moderately or extremely stressful compared with women providing no care was 1.05 (95% CI, 0.48–2.29), adjusting for reward. The multivariate RR of total CHD in women reporting moderately or extremely rewarding compared with women providing no care was 0.97 (95% CI, 0.47–2.02), adjusting for stress. Longer hours of caregiving to an ill spouse were modestly correlated with both higher level of reported stress (r =0.16) and reward (r =0.11). Similar trends could be found in ill parent caregivers: stress (r =0.28) and reward (r =0.19).
      Table 4Relative risk of CHD according to caregiving stress and reward experienced from any care recipients
      Giving no careNot at all or Just a little bitModerately or extremely
      CHD cases for stress
      Total number of cases for caregiving stress (n=316) and reward (n=315) may be different from the total number of cases (n=321) in the study due to women who did not report on caregiving stress or reward.
      15210443
      Stress
      Age-adjusted RR1.001.11 (0.88–1.45)1.07 (0.76–1.51)
      Multivariate RR
      See footnote a in Table 2.
      1.001.11 (0.86–1.42)0.96 (0.68–1.35)
      Stress (adjusting for reward)
      Age-adjusted RR1.001.11 (0.53–2.32)1.12 (0.52–2.41)
      Multivariate RR
      See footnote a in Table 2.
      1.001.16 (0.55–2.43)1.05 (0.48–2.29)
      CHD cases for reward
      Total number of cases for caregiving stress (n=316) and reward (n=315) may be different from the total number of cases (n=321) in the study due to women who did not report on caregiving stress or reward.
      1498142
      Reward
      Age-adjusted RR1.000.69 (0.34–1.42)1.14 (0.91–1.44)
      Multivariate RR
      See footnote a in Table 2.
      1.000.65 (0.32–1.34)1.09 (0.86–1.37)
      Reward (adjusting for stress)
      Age-adjusted RR1.000.62 (0.23–1.71)1.03 (0.50–2.13)
      Multivariate RR
      See footnote a in Table 2.
      1.000.60 (0.22–1.66)0.97 (0.47–2.02)
      CHD, coronary heart disease; CI, confidence interval; RR, relative risk.
      a Total number of cases for caregiving stress (n=316) and reward (n=315) may be different from the total number of cases (n=321) in the study due to women who did not report on caregiving stress or reward.
      b See footnote a in Table 2.

      Discussion

      To our knowledge, these prospective data are the first to suggest that high levels of caregiving burden for spouses may increase the risk of CHD among women. A strength of the present study is that we controlled for a very broad range of behavioral and dietary factors that could account for the differences in CHD risk between caregivers and noncaregivers.
      Caregiving to a disabled or ill spouse ≥9 hours a week increased the risk of CHD almost two-fold, and this association remained even after controlling for various risk factors of CHD. The mental distress from seeing loved ones suffer, added to the stress from financial burdens and the pressures of juggling work with caregiving, may have contributed to risk of CHD in caregivers. We lacked data on the financial burden associated with caregiving for disabled or ill spouses. The financial burden is two-fold: first, because of the extra medical expenses associated with the spouse’s illness; and second, because caring for an ill spouse may force the caregiver to give up or reduce time spent in paid work. Thus, the added stress on household finances may be an additional pathway (besides caregiving burdens) that could increase the risk of CHD in family members, or financial burdens may be an additional mediating factor between caregiving burden and risk of CHD.
      Caregivers are less likely to have time to engage in self-care and preventive health behavior than women who do not provide care. Furthermore, caregiving may reduce time to socialize with other people and may thus diminish opportunities to receive social support. Caregivers may alter normal patterns of diet, exercise, and other health-related behaviors in response to the stress of providing care. However, on the basis of the similarity between our age-adjusted models and multivariate models, it is unlikely that the deleterious effect of caregiving is solely mediated through behavioral mechanisms. Caregiving stress may reduce immune function and bring about adverse endocrine changes. Kiecolt-Glaser et al.
      • Kiecolt-Glaser J.
      • Glaser R.
      • Gravenstein S.
      • Malarkey W.
      • Sheridan J.
      Chronic stress alters the immune response to influenza virus vaccine in older adults.
      demonstrated that caregivers for spouses have a poorer antibody response following influenza vaccination than control subjects. Another study by the same authors
      • Kiecolt-Glaser J.
      • Marucha P.
      • Malarkey W.
      • Mercado A.
      • Glaser R.
      Slowing of wound healing by psychological stress.
      provided evidence that wound healing was significantly delayed in spouse caregivers compared with controls.
      Notably, providing care to a disabled or ill parent or disabled/ill others did not significantly increase the risk of CHD among women in our study. We hypothesize that this difference reflects the intensity of commitment involved in caring for a spouse compared to caring for other relatives. While caregiving for a disabled or ill spouse is often inescapable, caregiving for parents and other relatives tends to be more voluntary or shared between siblings and others. Furthermore, there is possibly more mental distress in caring for a sick spouse compared to a sick parent or sick others due to the greater threat of financial insecurity.
      In the present study, we did not observe a relation between the degree of caregiving stress/reward and risk of CHD. High hours of caregiving seemed to matter more than the stress or reward associated with caregiving. Asking about stress/reward did not appear to predict CHD risk. This may be partly because of the way we asked about stress, which mixed the stress resulting from all types of caregiving. On the other hand, relatively few women (17%) provided more than one type of care. Supplementing self-report with more objective measures of stress, such as salivary cortisol levels, might have improved our assessment.
      There are several limitations in our study. First, we lacked information on the illness or disability that required caregiving. Second, we lacked information on the duration of caregiving. Although we gathered information on the weekly amount of time spent on caregiving, we could not determine if there was a cumulative effect of caregiving burden on CHD risk. Third, there may also be possible residual confounding leading to an underestimation of the effect of caregiving on CHD if women who provide care are healthier in the first place (healthy caregiver effect). Lastly, we had a relatively small number of CHD cases, which may have prevented us from having enough power.
      Only one previous study prospectively examined the adverse effect of caregiving on mortality risk. Schulz and Beach
      • Schulz R.
      • Beach S.B.
      Caregiving as a risk factor for mortality.
      examined the relationship between caregiving demands among older caregivers of spouses who have difficulty with at least one activity of daily living (ADL) or instrumental ADL due to physical or health problems with confusion and 4-year all-cause mortality, controlling for sociodemographic factors, prevalent clinical disease, and subclinical disease at baseline. The study involved 4.5 years of follow-up among 392 caregivers and 427 noncaregivers aged 66 to 96 years living in four U.S. communities. The authors reported that caregivers who experienced caregiver strain had a 1.63-fold increase (95% CI, 1.00–2.65) in all-cause mortality compared with noncaregiving controls. Due to the small sample size, however, that study lacked sufficient power to examine the effect of caregiving on cause-specific mortality or disease incidence.
      Our data suggest that taking care of a disabled or ill spouse increases the risk of CHD. In light of the growing number of caregivers in society, consideration should be given to policies that alleviate the burdens of caregiving. Such policies might include an expansion in the coverage of the Family Medical Leave Act 1996, as well as private-sector solutions, such as providing flexibility in work schedules.

      Acknowledgements

      This research was funded by a grant from the National Institute of Aging Research (R01-AG-12806) and by the Dana Foundation. The Nurses’ Health Study was funded by a grant from the National Institutes of Health (P01-CA-87969). We are grateful to the members of the Nurses’ Health Study for their continuing participation and support. We also wish to acknowledge the advice and guidance of Diana Chapman Walsh, MD, and Sol Levine, MD, in conceiving the study of developing a measure of caregiving.

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