ORIGINAL
PAPER
Left Ventricular Mass as a Risk Factor in the Oldest Old Michael Bursztyn, MD;1,2 David Leibowitz, MD;1,2 Irit Stessman-Lande, MD;1 Jeremy M. Jacobs, MBBS;1,3 Eliana Ein-Mor, MSc;1 Jochanan Stessman, MD1,3 From the Jerusalem Institute of Aging Research;1 Department of Medicine;2 and Department of Rehabilitation and Geriatrics, Hadassah-Hebrew University Medical Center Mount-Scopus, Hebrew University-Hadassah Medical School, Jerusalem, Israel3
In middle-aged and “young elderly” cohorts, higher left ventricular mass (LVM) is associated with worse outcomes. The authors examined LVM and 5-year mortality among community-dwelling 85-year-old patients. A representative sample (n=526, born 1920–1921) from the Jerusalem Longitudinal Cohort Study underwent echocardiography at age 85. LVM was indexed by body surface area (LVM-BSA) or height (LVM-Ht). Patients with higher LVM were less educated and sedentary and had poorer self-rated health, functional limitations, and
increased comorbidity. Five-year mortality was 21.7% (n=114). Adjusted 5-year mortality rates were increased for the two upper quintiles of LVM-BSA (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.05–3.06) and LVM-Ht (HR, 2.2; 95% CI, 1.2–3.5). A step up in mortality occurred around the third quintile corresponding with LVM-BSA 110 g/m2 or LVM-Ht 51 g/m2.7. Among the oldest old, elevated LVM is significantly associated with mortality. J Clin Hypertens (Greenwich).2015;17:874–879. ª 2015 Wiley Periodicals, Inc.
Cardiovascular care among the oldest old presents an increasing challenge for clinicians and health care providers, especially given the relatively high frequency of morbidity and death from cardiac causes in this population. Despite the increasing burden of long-term cardiovascular care among the growing number of oldest old, prospective data examining the incidence of abnormal cardiac structure and its association with mortality in this population are limited.1,2 Previous studies that have used echocardiography in elderly patients to examine prognosis have included a broad range of ages, with relatively few patients aged older than 80 years.3–5 In addition, existing studies in older populations have generally been performed in the hospital or in an outpatient clinic setting, possibly contributing to a biased study population in this particular age group, as patients may have difficulty in leaving their homes.6 The recent introduction of portable echocardiographic instruments makes it possible to study patients in their homes and assess a more representative population of the oldest old. As was shown many years ago by the late Robert Tarazi, hypertrophy of the left ventricle (LVH) is a potentially reversible risk factor.3 It has also been long known to be associated with adverse cardiovascular outcomes in both the general and elderly populations.4–9 However, LVH is strongly affected by body size, and there is no consensus on how it should be indexed. The two most commonly used forms of adjustment of left ventricular (LV) mass (LVM) for body size are either by
body surface area (BSA)10 or by height alone. Because height is unidimensional but cardiac structure is threedimensional, the more commonly accepted method of indexation is by height2.7 (LVM-Ht).11 This method has the advantage of being relatively insensitive to sex. It is important to note that the commonly used indexed definitions of normal LVM are derived from middle-aged cohorts, with limited data from elderly cohorts. Therefore, data regarding normative values of LVH and their relationship to mortality in the “oldest old” are lacking. The objective of the present study is to identify normal upper limits for LVM as the cutoff point beyond which mortality is found to significantly increase in this population measured with home echocardiography among a representative sample of community-dwelling 85-year-old patients (“oldest old”).
Address for correspondence: Michael Bursztyn, MD, Department of Medicine, Hadassah-Hebrew University Medical Center Mount-Scopus, Hebrew University-Hadassah Medical School, PO Box 24035, Jerusalem 91240, Israel E-mail: [email protected] Manuscript received: February 14, 2015; revised: April 4, 2015; accepted: April 8, 2015 DOI: 10.1111/jch.12594
874
The Journal of Clinical Hypertension
Vol 17 | No 11 | November 2015
METHODS Participants were recruited from the Jerusalem Longitudinal Cohort Study, which was initiated in 1990 and has followed an age-homogenous representative cohort of West Jerusalem residents born from June 1920 to May 1921. The methods have been described elsewhere in detail.12–14 In the present study, we examined data from the third phase of data collection, which took place during 2005 and 2006. Patients were interviewed and examined in their homes on two separate occasions. The first session was composed of a structured interview that lasted about 1.5 hours. Information was collected in socioeconomic, demographic, medical, functional, cultural, and cognitive domains. The second session consisted of a medical examination. The institutional ethics committee of the Hadassah–Hebrew University Medical Center approved the study design, and written informed consent was obtained from all participants. Patients identified from the electoral register were randomly chosen from the total sample of individuals born in 1920 and 1921 and living in Jerusalem in 2005.
LVH and Mortality in the Elderly | Bursztyn et al.
Random numbers were used to choose patients from the electoral register according to their ID numbers. Patients in the study group who were not enrolled in the echocardiographic substudy had near-identical mortality and morbidity rates as those in the echocardiographic substudy. Furthermore, the representative nature of the total study population in comparison to the overall same age stratum of the Jerusalem population has previously been described.14 Mortality- and hospital-specific morbidity rates were found to be similar among patients enrolled in the study, compared with mortality and hospital morbidity data of patients who were invited to enroll in the study but declined, as well as compared with patients from the birth cohort who were not approached to enroll in the study. Sitting blood pressure with the arm supported at the heart level was measured three times with the use of a validated electronic sphygmomanometer (Omron 705IT; Omron Healthcare, Inc, Lake Forest, IL) according to the recommendations of the European Society of Hypertension at both occasions. Hypertension was defined as treatment with antihypertensive medications or average blood pressure >140 mm Hg systolic or 90 mm Hg diastolic (average of six measurements). Diagnosis of ischemic heart disease (IHD) was based on a history of hospitalization for myocardial infarction or acute coronary syndromes, coronary catheterization with evidence of significant coronary artery disease, positive stress test results, and a history typical for angina pectoris on exertion or previous coronary artery revascularization. Hyperlipidemia was defined as use of cholesterol-lowering medications. Diabetes mellitus was a composite of hypoglycemic medications, personal history, or a medical record diagnosis. Congestive heart failure (CHF) was based on hospital discharge diagnosis and according to examining research physician diagnosis at the time of examination at home. Self-rated health was assessed according to the question: “How do you rate your general health?” Possible responses were “good” and “poor,” using a Mini-Mental State Examination (MMSE) score 110 g/m2 in women.20 The second definition was performed by indexing LVM to height2.7 with a sex-independent cutoff >51 g/m2.7 (LVM-Ht).20 We determined quintiles for LVM indexed by either body surface area (LVM-BSA g/m2) or by height2.7 (LVM-Ht m2.7). Descriptive statistics were calculated, and because the cardiac parameter data were normally distributed, results are described as meanstandard deviation. Percentages were calculated as appropriate. We divided the population by quintiles of LVM and examined allcause mortality. For continuous variables, differences between means were calculated using t tests, and cumulative survival was assessed using Kaplan-Meier analysis and log-rank tests for statistical significance. Adjusted and unadjusted Cox proportional hazards models were performed. All models were adjusted for sex, education, self-rated health, physical activity, diabetes, IHD, hypertension, and either LVM-BSA or LVM-Ht. When analyzing LVM-BSA, we did not adjust for weight and height (included in the formula), and when it was indexed by height2.7 (LVM-Ht), only weight adjustments were made to refrain from overadjustment. Survival status at 5-year follow-up was assessed through the centralized Ministry of Interior database. Follow-up was available for all study patients. All P values were two-tailed and P=.05 was considered significant. Data storage and analysis were performed using SAS version 9.1e (SAS Institute Inc, Cary, NC).
RESULTS Of the 526 participants with available echocardiographic data, there were 248 men and 278 women. The Journal of Clinical Hypertension
Vol 17 | No 11 | November 2015
875
LVH and Mortality in the Elderly | Bursztyn et al.
pressure (LVM-BSA relationship to blood pressure: r=0.05, P=.2; LVM-Ht r=0.06, P=.16). In Table II, LVM is presented for survivors and those who died during the 5 years of follow-up. Survivors had significantly lower LVM according to LVMI-BSA and LVH-Ht for both men and women. There was good agreement in LVM-BSA and LVH-Ht in the quintiles (j=0.8, P
PAPER
Left Ventricular Mass as a Risk Factor in the Oldest Old Michael Bursztyn, MD;1,2 David Leibowitz, MD;1,2 Irit Stessman-Lande, MD;1 Jeremy M. Jacobs, MBBS;1,3 Eliana Ein-Mor, MSc;1 Jochanan Stessman, MD1,3 From the Jerusalem Institute of Aging Research;1 Department of Medicine;2 and Department of Rehabilitation and Geriatrics, Hadassah-Hebrew University Medical Center Mount-Scopus, Hebrew University-Hadassah Medical School, Jerusalem, Israel3
In middle-aged and “young elderly” cohorts, higher left ventricular mass (LVM) is associated with worse outcomes. The authors examined LVM and 5-year mortality among community-dwelling 85-year-old patients. A representative sample (n=526, born 1920–1921) from the Jerusalem Longitudinal Cohort Study underwent echocardiography at age 85. LVM was indexed by body surface area (LVM-BSA) or height (LVM-Ht). Patients with higher LVM were less educated and sedentary and had poorer self-rated health, functional limitations, and
increased comorbidity. Five-year mortality was 21.7% (n=114). Adjusted 5-year mortality rates were increased for the two upper quintiles of LVM-BSA (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.05–3.06) and LVM-Ht (HR, 2.2; 95% CI, 1.2–3.5). A step up in mortality occurred around the third quintile corresponding with LVM-BSA 110 g/m2 or LVM-Ht 51 g/m2.7. Among the oldest old, elevated LVM is significantly associated with mortality. J Clin Hypertens (Greenwich).2015;17:874–879. ª 2015 Wiley Periodicals, Inc.
Cardiovascular care among the oldest old presents an increasing challenge for clinicians and health care providers, especially given the relatively high frequency of morbidity and death from cardiac causes in this population. Despite the increasing burden of long-term cardiovascular care among the growing number of oldest old, prospective data examining the incidence of abnormal cardiac structure and its association with mortality in this population are limited.1,2 Previous studies that have used echocardiography in elderly patients to examine prognosis have included a broad range of ages, with relatively few patients aged older than 80 years.3–5 In addition, existing studies in older populations have generally been performed in the hospital or in an outpatient clinic setting, possibly contributing to a biased study population in this particular age group, as patients may have difficulty in leaving their homes.6 The recent introduction of portable echocardiographic instruments makes it possible to study patients in their homes and assess a more representative population of the oldest old. As was shown many years ago by the late Robert Tarazi, hypertrophy of the left ventricle (LVH) is a potentially reversible risk factor.3 It has also been long known to be associated with adverse cardiovascular outcomes in both the general and elderly populations.4–9 However, LVH is strongly affected by body size, and there is no consensus on how it should be indexed. The two most commonly used forms of adjustment of left ventricular (LV) mass (LVM) for body size are either by
body surface area (BSA)10 or by height alone. Because height is unidimensional but cardiac structure is threedimensional, the more commonly accepted method of indexation is by height2.7 (LVM-Ht).11 This method has the advantage of being relatively insensitive to sex. It is important to note that the commonly used indexed definitions of normal LVM are derived from middle-aged cohorts, with limited data from elderly cohorts. Therefore, data regarding normative values of LVH and their relationship to mortality in the “oldest old” are lacking. The objective of the present study is to identify normal upper limits for LVM as the cutoff point beyond which mortality is found to significantly increase in this population measured with home echocardiography among a representative sample of community-dwelling 85-year-old patients (“oldest old”).
Address for correspondence: Michael Bursztyn, MD, Department of Medicine, Hadassah-Hebrew University Medical Center Mount-Scopus, Hebrew University-Hadassah Medical School, PO Box 24035, Jerusalem 91240, Israel E-mail: [email protected] Manuscript received: February 14, 2015; revised: April 4, 2015; accepted: April 8, 2015 DOI: 10.1111/jch.12594
874
The Journal of Clinical Hypertension
Vol 17 | No 11 | November 2015
METHODS Participants were recruited from the Jerusalem Longitudinal Cohort Study, which was initiated in 1990 and has followed an age-homogenous representative cohort of West Jerusalem residents born from June 1920 to May 1921. The methods have been described elsewhere in detail.12–14 In the present study, we examined data from the third phase of data collection, which took place during 2005 and 2006. Patients were interviewed and examined in their homes on two separate occasions. The first session was composed of a structured interview that lasted about 1.5 hours. Information was collected in socioeconomic, demographic, medical, functional, cultural, and cognitive domains. The second session consisted of a medical examination. The institutional ethics committee of the Hadassah–Hebrew University Medical Center approved the study design, and written informed consent was obtained from all participants. Patients identified from the electoral register were randomly chosen from the total sample of individuals born in 1920 and 1921 and living in Jerusalem in 2005.
LVH and Mortality in the Elderly | Bursztyn et al.
Random numbers were used to choose patients from the electoral register according to their ID numbers. Patients in the study group who were not enrolled in the echocardiographic substudy had near-identical mortality and morbidity rates as those in the echocardiographic substudy. Furthermore, the representative nature of the total study population in comparison to the overall same age stratum of the Jerusalem population has previously been described.14 Mortality- and hospital-specific morbidity rates were found to be similar among patients enrolled in the study, compared with mortality and hospital morbidity data of patients who were invited to enroll in the study but declined, as well as compared with patients from the birth cohort who were not approached to enroll in the study. Sitting blood pressure with the arm supported at the heart level was measured three times with the use of a validated electronic sphygmomanometer (Omron 705IT; Omron Healthcare, Inc, Lake Forest, IL) according to the recommendations of the European Society of Hypertension at both occasions. Hypertension was defined as treatment with antihypertensive medications or average blood pressure >140 mm Hg systolic or 90 mm Hg diastolic (average of six measurements). Diagnosis of ischemic heart disease (IHD) was based on a history of hospitalization for myocardial infarction or acute coronary syndromes, coronary catheterization with evidence of significant coronary artery disease, positive stress test results, and a history typical for angina pectoris on exertion or previous coronary artery revascularization. Hyperlipidemia was defined as use of cholesterol-lowering medications. Diabetes mellitus was a composite of hypoglycemic medications, personal history, or a medical record diagnosis. Congestive heart failure (CHF) was based on hospital discharge diagnosis and according to examining research physician diagnosis at the time of examination at home. Self-rated health was assessed according to the question: “How do you rate your general health?” Possible responses were “good” and “poor,” using a Mini-Mental State Examination (MMSE) score 110 g/m2 in women.20 The second definition was performed by indexing LVM to height2.7 with a sex-independent cutoff >51 g/m2.7 (LVM-Ht).20 We determined quintiles for LVM indexed by either body surface area (LVM-BSA g/m2) or by height2.7 (LVM-Ht m2.7). Descriptive statistics were calculated, and because the cardiac parameter data were normally distributed, results are described as meanstandard deviation. Percentages were calculated as appropriate. We divided the population by quintiles of LVM and examined allcause mortality. For continuous variables, differences between means were calculated using t tests, and cumulative survival was assessed using Kaplan-Meier analysis and log-rank tests for statistical significance. Adjusted and unadjusted Cox proportional hazards models were performed. All models were adjusted for sex, education, self-rated health, physical activity, diabetes, IHD, hypertension, and either LVM-BSA or LVM-Ht. When analyzing LVM-BSA, we did not adjust for weight and height (included in the formula), and when it was indexed by height2.7 (LVM-Ht), only weight adjustments were made to refrain from overadjustment. Survival status at 5-year follow-up was assessed through the centralized Ministry of Interior database. Follow-up was available for all study patients. All P values were two-tailed and P=.05 was considered significant. Data storage and analysis were performed using SAS version 9.1e (SAS Institute Inc, Cary, NC).
RESULTS Of the 526 participants with available echocardiographic data, there were 248 men and 278 women. The Journal of Clinical Hypertension
Vol 17 | No 11 | November 2015
875
LVH and Mortality in the Elderly | Bursztyn et al.
pressure (LVM-BSA relationship to blood pressure: r=0.05, P=.2; LVM-Ht r=0.06, P=.16). In Table II, LVM is presented for survivors and those who died during the 5 years of follow-up. Survivors had significantly lower LVM according to LVMI-BSA and LVH-Ht for both men and women. There was good agreement in LVM-BSA and LVH-Ht in the quintiles (j=0.8, P
