Journal of Cardiac Failure Vol. 24 No.

9 2018

Clinical Investigation
Sex-Specific Trends in Incidence and Mortality for Urban and
Rural Ambulatory Patients with Heart Failure in Eastern Ontario
from 1994 to 2013
D1X X
LOUISE D2X X
Y. SUN, MD, SM,1,2,3 JACK D3X X D4X X
V. TU, MD, D5X X
PhD,2,4 HEATHER D6X X
SHERRARD, BScN, MHA, CHE,5 NORVINDAD7X X RODGER, MPH,D8X X 5

D9X X
THAIS COUTINHO, MD, D10X X 6,7,8
D1X X
MICHELE TUREK, MD,D12X X 6,9
D13X X
ELIZABETH D14X X
CHAN, MD, 6
D15X X
HEATHER D16X X
TULLOCH, PhD, 7

D17X X
LISA MCDONNELL, MSc, D18X X MBA,7,8 AND LISA D19X X M. MIELNICZUK, MD, D20X X MSc6

Ottawa, Ontario, Ontario, and Toronto, Ontario, Canada

ABSTRACT

Background: Differences in outcomes have previously been reported between urban and rural settings
across a multitude of chronic diseases. Whether these discrepancies have changed over time, and how sex
may influence these findings is unknown for patients with ambulatory heart failure (HF). We examined the
temporal incidence and mortality trends by geography in these patients.
Methods and Results: We conducted a retrospective cohort study of 36,175 eastern Ontario residents who
were diagnosed with HF in an outpatient setting from 1994 to 2013. The primary outcome was 1-year mor-
tality. We examined temporal changes in mortality risk factors with the use of multivariable Cox propor-
tional hazard models. The incidence of HF decreased in women and men across both rural and urban
settings. Age-standardized mortality rates also decreased over time in both sexes but remained greater in
rural men compared with rural women.
Conclusions: The incidence of HF in the ambulatory setting was greater for men than women and greater
in rural than urban areas, but mortality rates remained higher in rural men compared with rural women. Fur-
ther research should focus on ways to reduce this gap in the outcomes of men and women with HF. (J Car-
diac Fail 2018;24:568 574)
Key Words: Heart failure, Gender, Rurality, Mortality.

Heart failure (HF) remains a significant cause of morbidity
and mortality, with an estimated lifetime risk of 1 in 5.1,2
From the 1Division of Cardiac Anesthesiology, Department of Anesthe-
siology and Pain Medicine, University of Ottawa Heart Institute, Ottawa,
Ontario, Canada; 2Institute for Clinical Evaluative Sciences, Ontario,
Canada; 3School of Epidemiology and Public Health, University of
Ottawa, Ottawa, Ontario, Canada; 4Sunnybrook Schulich Heart Centre,
University of Toronto, Toronto, Ontario, Canada; 5Clinical Services, Uni-
versity of Ottawa Heart Institute, Ottawa, Ontario, Canada; 6Division of
Cardiology, Department of Medicine, University of Ottawa Heart Institute,
Ottawa, Ontario, Canada; 7Division of Prevention and Rehabilitation,
University of Ottawa Heart Institute, Ottawa, Ontario, Canada; 8Canadian
Women’s Heart Health Centre, University of Ottawa Heart Institute,
Ottawa, Ontario, Canada and 9Division of Cardiology, Department of
Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada.
Manuscript received February 12, 2018; revised manuscript received
June 15, 2018; revised manuscript accepted July 25, 2018.
Reprint requests: Louise Y. Sun, Room H2410, 40 Ruskin St, Ottawa,
ON K1Y 4W7. Tel: 1-613-696-7381. E-mail: lsun@ottawaheart.ca
See page 573 for disclosure information.
1071-9164/$ - see front matter
© 2018 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.cardfail.2018.07.465
Despite the current era of goal-directed medical therapy, HF
continues to be a leading cause of admission to hospital, is
associated with a poor prognosis, and contributes to 35% of
total female cardiovascular mortality.3 Urban-rural differences
in morbidity, mortality, access to care, medication use, and
cost of care have been reported in many cohorts of cardiovas-
cular disease, including stroke,4 acute myocardial infarction,5
stable ischemic heart disease6 and acute heart failure7,8; only 1
of those reports addressed the sex differences in outcomes by
geographic place of residence.9 The authors demonstrated
lower mortality in urban versus rural men in a mixed inpatient
and ambulatory cohort.9 Current epidemiologic studies are
focused on acutely hospitalized patients and lack consideration
for geographic disparities, especially in the ambulatory setting.
This is important because most cases of HF are managed in
the ambulatory environment, where rurality influences day-to-
day health care delivery and health-seeking behavior. Various
definitions of rurality in published population-based studies,
ranging from the Rurality Index of Ontario (RIO)6,10 12 to

568
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 Heart Failure Mortality by Sex and Rurality  Sun et al
using the second character of the forward sortation address for
each patient’s home address (studies from the Canadian prov-
inces of Nova Scotia and Alberta),5,9 rurality status of admit-
ting hospital,8 the Geographic Information System (studies
from Maine in the USA),7 and the Scottish Household Survey
(studies from Northern Scotland).4 As part of a regional qual-
ity-of-care improvement initiative, we examined the sex- and
rurality-specific trends in HF incidence, mortality, and comor-
bidities in eastern Ontario, which became the Champlain Local
Health Integration Network (LHIN) in 2006.
Methods
Design, Study Population, and Data Sources
After approval from the Research Ethics Board of Sunny-
brook Health Sciences, Toronto, Canada, we conducted a
population-based retrospective cohort study of Champlain
LHIN residents aged 40 105 years who were diagnosed
with HF in an ambulatory setting from April 1, 1994, to
March 31, 2014. We excluded those with missing informa-
tion regarding age, sex, or rurality status.
Incident HF cases were identified from physician billings
based on a validated algorithm of
2 outpatient claims for HF
within 1 year.13 This validated algorithm was shown to have
85% sensitivity and 97% specificity in identifying HF events13
and allowed us to study a validated cohort of HF patients with
consistent entry criteria over time. We linked the LHIN data-
base for defining geographic LHIN building blocks, Registered
Persons Database (RPDB) for demographics and vital statistics,
the Canadian Institute for Health Information’s Discharge
Abstract Database (DAD) for comorbidities, and the Ontario
Health Insurance Plan (OHIP) database. Databases were linked
with the use of unique confidential codes and have been vali-
dated for many outcomes, exposures, and comorbidities.14 17
Exposure and Outcome
The primary exposure was rurality as graded with the use of
the RIO.10,18 The RIO was developed by the Ministry of Health
and Long-Term Care of Ontario to provide consistent geo-
graphic classifications according to postal code, based on a
community’s population, population density, and proximity to
both basic and tertiary health care. It is scaled ordinally from 0
to 100, with higher numbers indicating greater rurality. Consis-
tently with previous population-based studies,6,10 12 we classi-
fied urban as RIO 0 39 and rural as RIO
40. The primary
outcome was all-cause mortality within 1 year of HF diagnosis.
Covariates
Demographic variables were obtained from the RPDB. We
estimated socioeconomic status based on patients’ neighbor-
hood median income in the Canadian census,19 and identified
hypertension,14 asthma,20 chronic obstructive pulmonary dis-
ease (COPD),21 and diabetes mellitus16 with the use of vali-
dated algorithms. Other comorbidities were identified with the
use of DAD, SDS, and OHIP based on International Classifica-
tion of Diseases, 10th Revision codes within 5 years before HF
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569
diagnosis, using previously described methods.22,23 Our choice
of covariates is consistent with those used in previous popula-
tion-based studies evaluating outcomes of patients with HF.9,24
Frailty was identified with the use of the Johns Hopkins
Adjusted Clinical Groups frailty-defining diagnoses indicator,
which is an instrument designed and validated for research of
frailty-related outcomes and resource utilization according to
administrative data.25 29
Statistical Analysis
Continuous variables were expressed as mean (SD) and cate-
goric variables as number (proportion). Survival time was
defined from date of HF diagnosis to death or last follow-up.
Censoring occurred at the loss of OHIP eligibility. We plotted
age-standardized HF incidence and 1-year mortality by sex and
rurality, with the 1991 Canadian population
40 years old as
the reference population. To elucidate temporal changes in dem-
ographics and comorbidities, we divided the population into
four 5-year cohorts and studied the “historical” (those diagnosed
with HF in the 1994 1998 fiscal years) and “modern”
(2009 2013 fiscal years) cohorts. These temporal boundaries
were chosen to ensure equal time-frame representation in each
group, and to allow for comparison of outcomes in the historical
and modern cohorts without the overlapping interference of
neighboring years (eg, medical practice and outcomes in 1998
were likely very similar to those in 1999). The relative hazard of
death was assessed by means of Cox proportional hazard models
with multivariable adjustment. We used multiplicative interac-
tion terms to identify sex- and rurality-specific mortality risk fac-
tors. Analyses were performed with the use of SAS 9.3 (Cary,
North Carolina), with statistical significance defined by P < .05.
Results
Over the 20-year period, a total of 36,175 ambulatory HF
diagnoses were made in eastern Ontario, 51% of them in
women. There were 9,653 incident HF cases in the histori-
cal cohort (54% women) and 9,027 in the modern cohort
(49% women). HF incidence declined in a stable pattern
and remained higher in the rural setting (Fig. 1). Standard-
ized 1-year mortality rates (SMRs) had declined in both
sexes; it remained greater in rural men than rural women
(Fig. 2A) and was at most time points similar in both sexes
in the urban setting (Fig. 2B).
Table 1 presents the characteristics of rural versus urban
patients in the historical and modern cohorts. In the modern
HF cohort, a greater proportion of high-income earners was
observed in the rural setting. Modern rural patients were
more likely than urban patients to be younger and to have
atrial fibrillation, ischemic heart disease, valvular disease,
peripheral arterial disease (PAD), cerebrovascular disease
(CVD), chronic obstructive pulmonary disease (COPD),
asthma, and depression, but less likely to have pulmonary
circulatory disease, renal disease, anemia, metastatic can-
cer, and venous thromboembolism and to be frail.
Table 2 lists the multivariable predictors of 1-year mor-
tality in the historical and modern cohorts. Rurality was not
570 Journal of Cardiac Failure Vol. 24 No. 9 September 2018
Fig. 1. Temporal trends in age-standardized ambulatory heart
failure incidence rates in the Champlain Local Health Integration
Network, by sex and rurality.
an independent correlate of mortality in neither cohort.
Women had a lower risk of mortality than men in the histor-
ical cohort but not in the modern era. Compared with the
historical era, the mortality risk associated with age >65
Fig. 2. (A) Age-standardized trends in mortality rates within 1
year of ambulatory heart failure diagnosis in rural patients, by sex.
The dashed line represents incidence rates in men, the solid line
incidence rates in women. (B) Age-standardized trends in mortality
within 1 year of ambulatory heart failure diagnosis in urban
patients, by sex. The dashed line represents incidence rates in men,
the solid line incidence rates in women.
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years, liver disease, and primary malignancy had increased
in the modern cohort, while the risk associated with valvu-
lar disease, chronic renal disease, diabetes and metastatic
malignancy had diminished. In addition, pulmonary circula-
tory disease, COPD/asthma, and alcohol abuse had emerged
as new mortality risk factors, whereas comorbidities such as
PAD, CVD, depression, psychosis, and paraplegia were no
longer risk factors in the modern era.
The rurality-specific (Table 3) and sex-specific (Table 4)
mortality risk factors have evolved over time. Specifically, in
the historical cohort, valvular disease, dementia, and liver dis-
ease were stronger predictors of mortality in rural than in
urban patients. In the modern cohort, lower income (quintile
2) was associated with a lower risk of death only in rural
patients, and metastatic cancer was associated with a higher
mortality risk in rural than in urban patients. Regarding sex
in the historical cohort, hypertension (likely reflecting less
severe heart disease, which is often accompanied by hypoten-
sion) was more protective in women than men. Also, anemia
was associated with a higher risk of death in men, and renal
disease and primary malignancy were associated with a
higher risk of death in women. Over time, anemia maintained
a stable risk profile in both sexes, the risk associated with pri-
mary malignancy had increased in men, and CVD had
emerged as a new risk factor in women.
Discussion
Geographic variations and their relationships to sex have
not been evaluated in detail in ambulatory HF patients, and
the present study adds to this body of literature. We found a
decline in HF incidence and mortality in urban and rural east-
ern Ontario over a 20-year period. However, HF incidence
remained greater for men than women in both geographic
settings, and mortality remained greater in rural men than in
rural women and was similar in urban men and women.
Our study corroborates other population-based studies in
noting an overall decline in HF incidence.24,30 Murphy et
al, in a study of hospitalized patients, found no differences
in 1-year mortality between rural and urban cohorts, despite
a lower prescription rate of evidence-based therapies in
rural HF patients.31 Gamble et al evaluated geographic dis-
parities in HF outcomes in Alberta, Canada, and found
lower mortality in urban versus rural men but no geographic
differences in female mortality.9 They attributed this geo-
graphic disparity to urban patients being more likely than
rural patients to have an office-based visit and less likely to
be admitted to hospital or an emergency department within
a year of HF diagnosis. The present study, in contrast, found
no geographic differences in mortality but instead found
poorer survival in rural men compared with rural women.
This discrepancy may be explained in part by differences in
baseline risk. Specifically, the Gamble et al cohort consisted
of both hospitalized and ambulatory HF patients whereas
our cohort consisted exclusively of ambulatory patients. In
addition, there was a greater preponderance of Indigenous
people in rural Alberta, representing a different
 Heart Failure Mortality by Sex and Rurality  Sun et al 571

Table 1. Temporal Trends in Characteristics of Incident Heart Failure Patients in the Historical and Modern Cohorts, n (%)

Historical Cohort (1994 1999) Modern Cohort (2009 2014)

Variable
Rural (n = 2209) Urban (n = 7444) P Value Rural (n = 1811) Urban (n = 7213) P Value

Sociodemographics
Age, y (mean § SD) 73.6 § 11.2 74.8 § 11.0 <.001 73.5 § 12.0 73.9 § 13.0 <.001

Age group

40 64 y 390 (17.7%) 1290 (17.3%) <.001 425 (23.5%) 1778 (24.6%) <.001
65 74 y 666 (30.1%) 1977 (26.6%) 457 (25.2%) 1515 (21.0%)
75 84 y 726 (32.9%) 2734 (36.7%) 554 (30.6%) 2190 (30.4%)

85 y 391 (17.7%) 1443 (19.4%) 375 (20.7%) 1730 (24.0%)

Income quintile

Missing 5 (0.1%) 0 (0.0%) <.001 9 (0.5%) 5 (0.1%) <.001

1 (low) 576 (26.1%) 1419 (19.1%) 430 (23.7%) 1432 (19.9%)
2 510 (23.1%) 1527 (20.5%) 359 (19.8%) 1440 (20.0%)
3 453 (20.5%) 1402 (18.8%) 353 (19.5%) 1674 (23.2%)
4 353 (16.0%) 1411 (19.0%) 274 (15.1%) 1508 (20.9%)
5 (high) 316 (14.3%) 1685 (22.6%) 377 (20.8%) 1157 (16.0%)

Comorbidities

Benign HTN 1353 (61.2%) 4475 (60.1%) <.001 1279 (70.6%) 5071 (70.3%) <.001
Complicated HTN 88 (4.0%) 394 (5.3%) .002 124 (6.8%) 586 (8.1%) .543
Atrial fibrillation 183 (8.3%) 646 (8.7%) .144 256 (14.1%) 928 (12.9%) .116
IHD 314 (14.2%) 967 (13.0%) <.001 484 (26.7%) 1557 (21.6%) <.001
Valvular disease 68 (3.1%) 248 (3.3%) .524 166 (9.2%) 549 (7.6%) <.001
PAD 127 (5.7%) 468 (6.3%) <.001 84 (4.6%) 277 (3.8%) <.001
CVD 209 (9.5%) 711 (9.6%) .954 116 (6.4%) 353 (4.9%) .173
Pulmonary circulatory 7 (0.3%) 40 (0.5%) .448 28 (1.5%) 161 (2.2%) .006
disease
COPD/asthma 684 (27.5%) 2435 (32.7%) <.001 785 (43.3%) 2733 (37.9%) <.001
Alcohol abuse 13 (0.9%) 43 (5.8%) .224 37 (2.0%) 123 (1.7%) .010
Chronic renal disease 45 (2.0%) 187 (2.5%) .089 71 (3.9%) 321 (4.5%) .035
Diabetes 435 (19.7%) 1480 (19.9%) <.001 605 (33.4%) 2476 (34.3%) <.001
Hypothyroidism 49 (2.2%) 195 (2.6%) <.001 44 (2.4%) 170 (2.4%) <.001
Liver disease 23 (1.0%) 93 (1.2%) .249 23 (1.3%) 111 (1.5%) .444
Anemia 84 (3.8%) 332 (4.5%) <.001 141 (7.8%) 692 (9.6%) <.001
Dementia 67 (3.0%) 304 (4.1%) .003 76 (4.2%) 288 (4.0%) .002
Depression 81 (3.7%) 219 (2.9%) <.001 59 (3.3%) 164 (2.3%) <.001
Psychosis 71 (3.2%) 295 (4.0%) <.001 10 (0.6%) 40 (0.6%) .950
Primary tumor 158 (7.2%) 557 (7.5%) .008 161 (8.9%) 609 (8.4%) .017
Metastatic cancer 35 (1.6%) 146 (2.0%) .658 30 (1.7%) 171 (2.4%) .288
Paraplegia 38 (1.7%) 162 (2.2%) .399 20 (1.1%) 88 (1.2%) .587
VTE 33 (1.5%) 176 (2.4%) .157 16 (0.9%) 83 (1.2%) .070
Frailty 299 (13.5%) 1336 (17.9%) <.001 373 (20.6%) 1735 (24.1%) <.001

HTN, hypertension; IHD, ischemic heart disease; PAD, peripheral arterial disease; CVD, cerebrovascular disease; COPD, chronic obstructive pulmonary
disease; VTE, venous thromboembolism.

sociodemographic and genetic makeup, and possibly symp-
tom awareness and health-seeking behavior, than those
residing in rural eastern Ontario. Further research is war-
ranted to define the social factors that influence health care
access and delivery in diverse geographic settings.
In evaluation of the temporal changes of comorbidities in
urban and rural cohorts, we found the rural demographic to
be younger, less frail, and generally of lower income status
compared with their urban counterparts. This has been
observed in other population-based studies30 and speaks to
the increasing complexity of HF sociodemographics in the
current era. Eastern Ontario is a geographically large and
diverse area where HF care can be delivered by a variety of
providers ranging from nurse practitioners to cardiologists
from private practices, family health teams, and community
and tertiary care hospitals (Fig. 3). In 2006, the province
established LHINs to plan, fund, and integrate health care
services for more efficient and coordinated care in the
regions. In this context, it is anticipated that significant varia-
tions in care and outcomes between urban and rural settings
would be minimized. We have indeed found no difference
between the SMRs of rural versus urban cohorts but have
identified sex as an important mortality risk factor in the rural
setting. The burden of comorbid disease has also changed
over time, with important increases in the prevalence of dis-
eases such as frailty, anemia, diabetes, chronic kidney dis-
ease, valve disease, and atrial fibrillation. In addition, there
are increasing proportions of young (40 64 y) and very
elderly (>85 y) patients with HF. This finding is similar to
the work of Christiansen et al, who identified an increased

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572 Journal of Cardiac Failure Vol. 24 No. 9 September 2018

Table 2. Multivariable Predictors of 1-Year Mortality in the incidence of HF in the youngest age cohort.30 Further
Historical (1994 1999) and Modern (2009 2013) Cohorts, research should therefore focus on ways to reduce this dispar-
Adjusted Hazard Ratio (95% Confidence Interval) ity in rural areas. The increased prevalence of multiple
Variable Historical Cohort Modern Cohort chronic diseases in HF patients has implications for care
delivery and resources needed to meet the needs of this com-
Age group plex population. This may be particularly relevant in patients
40 64 y Reference Reference
65 74 y 1.50 (1.24 1.82) 1.62 (1.31 2.01) living in rural areas, where access to care and specialists may
75 84 y 2.24 (1.87 2.69) 2.73 (2.25 3.32) be more challenging. From a practical assessment, it empha-

85 y 3.79 (3.13 4.58) 5.42 (4.47 6.58) sizes the importance of screening and diagnosis of these
Female 0.81 (0.73 0.89) 0.90 (0.81 1.01)
Rural 0.96 (0.85 1.08) 0.90 (0.79 1.04) comorbid conditions in patients presenting with HF.
Income Quintile
1 (low) 1.07 (0.92 1.25) 1.03 (0.92 1.16) Study Limitations
2 0.99 (0.85 1.16) 1.02 (0.92 1.14)
3 1.09 (0.94 1.27) 0.96 (0.86 1.07) The present study has several limitations. Our method of
4 0.98 (0.84 1.15) 0.94 (0.84 1.05)
5 (high) Reference Reference ascertaining HF cases may have led to underestimating the
Benign hypertension 0.72 (0.66 0.80) 0.79 (0.7 0.89) presence of HF.13,24 The lack of information on ejection frac-
Complicated hypertension 0.77 (0.60 0.98) 0.75 (0.60 0.94) tion precluded analyses by HF subtypes. Also, cohort studies
Atrial fibrillation 1.04 (0.88 1.23) 1.03 (0.89 1.20)
Ischemic heart disease 0.93 (0.80 1.08) 0.90 (0.78 1.03) are by nature subject to residual confounding. Despite these
Valvular disease 1.09 (0.84 1.43) 0.57 (0.44 0.75) limitations, this is the first large ambulatory HF study to pro-
Peripheral arterial disease 1.32 (1.10 1.57) 1.20 (0.94 1.55) duce detailed sex- and geographic-specific trends, using con-
Cerebrovascular disease 1.17 (1.00 1.38) 1.07 (0.85 1.35)
Pulmonary circulatory disease 1.00 (0.52 1.95) 1.60 (1.18 2.18) sistent entry criteria over a 20-year time period.
COPD/asthma 1.09 (0.99 1.21) 1.17 (1.05 1.30)
Alcohol abuse 1.06 (0.58 1.94) 1.46 (1.03 2.07)
Chronic renal disease 1.97 (1.58 2.46) 1.53 (1.25 1.87)
Conclusion
Diabetes 1.32 (1.17 1.49) 1.11 (1.00 1.25)
Hypothyroidism 1.09 (0.84 1.43) 0.98 (0.73 1.32)
Over a 20-year window, we found an overall decrease in
Liver disease 1.68 (1.15 2.44) 2.83 (2.04 3.92) ambulatory HF incidence and mortality in both urban and
Anemia 1.55 (1.28 1.86) 1.43 (1.23 1.67) rural settings. The incidence of ambulatory HF was greater
Dementia 1.74 (1.44 2.10) 1.79 (1.49 2.14)
Depression 1.29 (1.03 1.63) 1.30 (0.97 1.73)
for men than women, and greater in rural than urban areas.
Psychosis 1.37 (1.11 1.69) 1.34 (0.75 2.39) However, mortality rates in rural men remained higher than
Primary tumor 1.43 (1.21 1.69) 1.68 (1.42 1.98) in rural women at most time points. In addition, the burden
Metastatic cancer 3.74 (2.94 4.74) 2.68 (2.09 3.44)
Paraplegia 1.34 (1.00 1.79) 1.36 (0.9 2.05)
of comorbid disease has changed over time, with important
VTE 0.82 (0.59 1.13) 0.9 (0.58 1.39) increases in many chronic diseases associated with worse
morbidity and mortality. This has important implications in
Abbreviations as in Table 1.
the delivery of care to patients with HF who struggle with

Table 3. Rurality-Specific Risk Factors of 1-Year Mortality in the Historical (1994 1998) and Modern (2009 2013) Cohorts of
Ambulatory Patients With Heart Failure, Hazard Ratio (95% Confidence Interval)

Multiplicative
Interaction
Variable Rural Urban P Value*
Historical cohort

Valvular disease 3.43 (2.36 4.98) 1.48 (1.19 1.84) <.001

Dementia 3.49 (1.80 6.74) 1.26 (0.79 2.02) .008
Liver disease 2.15 (1.32 3.51) 0.90 (0.66 1.23) .008

Modern cohort
Income quintile

1 (lowest) 0.81 (0.55 1.19) 1.01 (0.83 1.23) .04

2 0.51 (0.33 0.77) 1.08 (0.90 1.29)
3 0.77 (0.52 1.15) 0.95 (0.79 1.14)
4 0.70 (0.46 1.07) 1.00 (0.84 1.19)
5 (highest) Reference Reference
Metastatic 6.50 (3.52 12.00) 2.36 (1.79 3.11) .0005
cancer

*Multiplicative interaction terms were formed by multiplying rurality by each of the covariates in the multivariable Cox proportional hazards model for 1-
year mortality. Only significant interaction terms (ie, ones demonstrating rurality-specific risk factors) were reported in this table.

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 Heart Failure Mortality by Sex and Rurality  Sun et al 573

Table 4. Sex-Specific Risk Factors of 1-Year Mortality in the Historical (1994 1998) and Modern (2009 2013) Cohorts of Ambulatory
Patients With Heart Failure, Hazard Ratio (95% Confidence Interval)

Variable Women Men Multiplicative Interaction P Value*

Historical cohort

Hypertension 0.66 (0.58 0.76) 0.80 (0.69 0.92) .04

Anemia 1.36 (1.07 1.74) 1.94 (1.45 2.59) .02
Renal disease 2.49 (1.81 3.44) 1.51 (1.1 2.08) .03
Primary tumor 1.69 (1.33 2.13) 1.22 (0.96 1.55) .01

Modern cohort

Cerebrovascular disease 1.42 (1.05 1.92) 0.74 (0.52 1.06) .04

Anemia 1.17 (0.94 1.45) 1.77 (1.42 2.21) .002
Primary tumor 1.38 (1.05 1.80) 1.98 (1.59 2.46) .02

*Multiplicative interaction terms were formed by multiplying sex by each of the covariates in the multivariable Cox proportional hazards model for one-
year mortality. Only significant interaction terms (ie, ones demonstrating sex-specific risk factors) were reported in this table.

Fig. 3. Map of the subregions of the Champlain Local Health Inte-
gration Network. As a rule of thumb, most of Western, Central and
Eastern Ottawa subregions are urban and the Western and Eastern
Champlain subregions are rural.
Funding
This work was supported by the Champlain Local
Health Integration Network. Dr Tu was supported as a
Canada Research Chair in Health Services Research and
by an Eaton Scholar Award from the Department of Medi-
cine, University of Toronto. Dr Coutinho holds the Univer-
sity of Ottawa Heart Institute’s Chair in Women’s Heart
Health and is a Clinician Scientist supported by a Heart
and Stroke Foundation of Ontario Clinician Scientist Phase
I Award. Dr Mielniczuk holds a University of Ottawa
Chair in Heart Failure and is supported as a Clinician Sci-
entist from the Heart and Stroke Foundation of Ontario.
The funders did not have a role in the design and conduct
of the study, in the collection, analysis, and interpretation
of the data, nor in the preparation, review, or approval of
the manuscript.

increasing disease complexity in both rural and urban sert-

tings. Our findings suggest that the delivery of health care
and provision of outreach and peer support programs for
A Note From The Editors
HF patients should be tailored to rurality and sex, and fur-
ther research should focus on ways to reduce this gap in The second author of this paper, Jack Tu, died tragically
outcomes in ambulatory patients with HF. at the age of 53 on May 30th 2018. It came as a shock to all
those who knew him. An internationally known cardiologist
Acknowledgments and health services researcher, Jack was brilliant, kind
hearted, remarkably productive and a major asset to the
This study was supported by the Institute for Clinical
University of Toronto. One of us (PJH) met Jack during his
Evaluative Sciences (ICES), which is funded by an annual
tenure at the Department of Health Care Policy at Harvard
grant from the Ontario Ministry of Health and Long-Term
Medical School in the early 1990s. It was already clear at
Care. The authors acknowledge the use of data compiled
that time that he was going to make a major impact. He was
and provided by the Canadian Institute for Health Informa-
also an irreplaceable mentor and colleague (to DSL). The
tion. These datasets were linked with the use of unique
current paper was expertly handled by our Guest Editor,
encoded identifiers and analyzed at ICES. The analyses,
Stephen Gottlieb;We are glad that we have a chance to see
conclusions, opinions and statements expressed in the man-
Jack’s name one more time in the JCF. It is a small tribute
uscript are those of the authors, and do not necessarily
to him that we let the peer review process determine the
reflect those of the above agencies.
fate of this paper. It is indeed a contribution that reflects
high quality work, so very emblematic of Jack and his
Disclosures
approach to cardiology and research. He will be missed.
None. Paul J. Hauptman, MD and Douglas S. Lee, MD, PhD.

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574 Journal of Cardiac Failure Vol. 24 No. 9 September 2018
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