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ORIGINAL ARTICLE
Increased risk of coronary heart disease in patients
with chronic osteomyelitis: a population-based study
in a cohort of 23 million
Lien-Cheng Hsiao,
1
Chih-Hsin Muo,
2
Yu-Ching Chen,
3
Che-Yi Chou,
4,5
Chun-Hung Tseng,
6,7
Kuan-Cheng Chang
1,4
1
Division of Cardiology,
Department of Internal
Medicine, China Medical
University Hospital, Taichung,
Taiwan
2
Institute of Environmental
Health, College of Public
Health, China Medical
University, Taichung, Taiwan
3
Department of Biomedical
Informatics, Asia University,
Taichung, Taiwan
4
Graduate Institute of Clinical
Medical Science, China
Medical University, Taichung,
Taiwan
5
Department of Nephrology,
China Medical University
Hospital, Taichung, Taiwan
6
Department of Neurology,
China Medical University
Hospital, Taichung, Taiwan
7
School of Medicine, China
Medical University, Taichung,
Taiwan
Correspondence to
Dr Kuan-Cheng Chang,
Division of Cardiology,
Department of Medicine, China
Medical University Hospital 2,
Yuh-Der Road, Taichung
40447, Taiwan;
kuancheng.chang@gmail.com
Dr Chun-Hung Tseng,
Department of Neurology,
School of Medicine, China
Medical University 91,
Hsueh-Shih Road, Taichung,
40402, Taiwan;
d8333@mail.cmuh.org.tw
Received 6 February 2014
Revised 10 April 2014
Accepted 14 May 2014
To cite: Hsiao L-C, Muo C-
H, Chen Y-C, et al. Heart
Published Online First:
[please include Day Month
Year] doi:10.1136/heartjnl-
2014-305652
ABSTRACT
Objectives Chronic inflammatory disease may trigger
vascular atherosclerosis. This study aimed to determine
whether chronic osteomyelitis (COM) is linked to an
increased risk of coronary heart disease (CHD).
Methods A national insurance claim dataset of more
than 23 million enrolees was used to identify 15 054
patients with newly diagnosed COM and 60 216
randomly selected age-matched and gender-matched
controls between 2001 and 2009 for comparing the risk
and incidence of CHD. The study period was from the
entry date to the first date of the following events: the
diagnosis of CHD, death, withdrawal from the Taiwan
National Health Insurance programme or the end of
2010. The analysis of the CHD risk was performed using
Cox proportional hazards regression model.
Results During a follow-up period of 67 927 person-
years, the overall incidence rate of CHD in COM cohort
was 1.95 times higher than non-COM cohort (16.66 vs
8.52 per 1000 person-years). After controlling age,
gender and four comorbidities (hypertension, diabetes,
hyperlipidaemia and stroke), the risk remained
significantly higher in the COM cohort than the control
group (adjusted HR=1.65, 95% CI 1.54 to 1.78,
p<0.001). In age-stratified analysis, the younger
population had a stronger association between COM
and CHD risk than the elderly (from HR=3.42, 95% CI
1.60 to 7.32 in age <35 to HR 1.39, 95% CI 1.15 to
1.68 in age ≥80).
Conclusions This study demonstrates that COM is an
independent risk factor for CHD, particularly in the
younger population. Further studies are necessary to
explore the underlying mechanisms linking COM and
CHD.
INTRODUCTION
Coronary heart disease (CHD), also known as cor-
onary artery disease (CAD), refers to a spectrum of
illnesses ranging from coronary atherosclerosis,
myocardial infarction and postinfarct heart
failure.
12
Nowadays, CHD remains one of the
major causes of mortality and morbidity in the
world.
3–5
Fortunately, with the introduction of life-
style modification, modern pharmacology and
innovative coronary intervention, the number of
CHD-associated death has been steadily reduced in
the past decades.
367
According to the Framingham Heart Study
(FHS) and following epidemiological studies, a
number of CHD risk factors, including
hypertension, hyperlipidaemia, diabetes mellitus,
obesity and smoking, have been identified to play
crucial roles in the pathogenesis of coronary artery
atherosclerosis and these so-called conventional
risk factors for CHD were helpful to predict the
risk of CHD.
389
On the other hand, lipoprotein
(a) (Lp(a)), homocysteinemia, hypercoagulability,
imbalanced oxidative stress and infection have been
investigated as novel issues (non-traditional risk
factors) in atherosclerotic disease, including
CHD.
310–13
Furthermore, it has been suggested
that atherosclerotic change, the main aetiology of
CHD, is an inflammatory process resulting from
mutual involvement of immune mechanisms and
metabolic risk factors.
14 15
Recently, it has been shown that patients with
chronic infl ammatory disease have an increased risk
of cardiovascular diseases.
16
For example, peri-
odontal disease, a chronic inflammatory disorder
caused by a chronic bacterial infection, has been
proposed to be associated with the development
and progression of CHD.
17
Similarly, chronic
osteomyelitis (COM), a long-term infection of
bone and bone marrow, could lead to a subsequent
chronic inflammatory process in the body.
18 19
To
improve CHD prevention and management, it
would be important to understand whether COM
serves as a novel risk factor in the development of
CHD. However, current knowledge regarding the
interaction between COM and CHD remains
limited. In the present study, we sought to deter-
mine the association of COM with the incidence
and risk of CHD using a nationwide insurance
dataset of 23 million enrolees in Taiwan.
METHODS
Data sources
This retrospective cohort study used inpatient data-
base, a part of National Health Insurance Research
Databases (NHIRDs), which was established by the
National Health Research Institutes (NHRI). NHRI
constructed all medical claims from the beneficiary
files in the NHI programme, which covered 98%
of Taiwan population since 1996.
20
According to
the Personal Information Protection Act, the identi-
fication code of patients was scrambled during
NHIRDs compiling before sent to researchers.
Due to the blindness of researchers to the patient
identities, this study escaped from the review of
Ethics Committee. The information included
birthday, gender, inpatient admission and discharge.
Hsiao L-C, et al. Heart 2014;0:1–5. doi:10.1136/heartjnl-2014-305652 1
Coronary artery disease
Heart Online First, published on June 4, 2014 as 10.1136/heartjnl-2014-305652
Copyright Article author (or their employer) 2014. Produced by BMJ Publishing Group Ltd (& BCS) under licence.
group.bmj.com on July 2, 2014 - Published by heart.bmj.comDownloaded from
A variety of personal health habits, such as physical activity,
smoking and alcohol consumption, were not available in the
Taiwan NHI dataset. The diagnosis of disease code was based
on the International Classification of Diseases, 9th Revision,
Clinical Modification (ICD-9-CM) in NHIRDs. NHI prevents
coding errors and misdiagnosis by regularly monitoring disease
coding and auditing claims submitted for reimbursement by hos-
pitals that contract with NHI to offer NHI participants inpatient
services. Hence, the consistent information could allow us to
conduct the present research of correlation between COM and
CHD.
Study population
All 15 054 patients with newly diagnosed osteomyelitis
(ICD-9-CM code 730.1) and without past history of coronary
heart disease (ICD-9-CM code 410, 411.1, 411.81, 411.89,
412, 413, 414.00–414.05, 414.8 and 414.9) were collected
from 2001 to 2009 as osteomyelitis cohort. The date of their
diagnosis of osteomyelitis was used as the entry date. The com-
parison group consisted of randomly selected insured people
without the history of osteomyelitis and CHD, matched with
the COM group across age strata (every 5 years), gender and the
entry-year and entry-month with a sample size fourfold of the
COM group. The comorbidities included hypertension
(ICD-9-CM code 401–405), diabetes mellitus (ICD-9-CM code
250), hyperlipidaemia (ICD-9-CM code 272.0–272.4) and
stroke (ICD-9-CM code 430–438) and were defined before the
entry date. The study period was from the entry date to the first
date of the following events: the diagnosis of CHD, death, with-
drawal from the NHI programme or the end of 2010.
Statistical analysis
All statistic analyses were performed with the use of the SAS
software V.9.1 (SAS Institute Inc, Carey, North Carolina, USA),
and the significant level was set at 0.05 for a two-tailed p value.
The difference of characteristics between two cohorts was ana-
lysed using χ
2
test. The incidence (per 1000 person-years) of
CHD was calculated and the HRs of CHD were estimated in
Cox proportional hazards regression. Model 1 was adjusted for
age and gender. Model 2 controlled age, gender, hypertension,
diabetes, hyperlipidaemia and stroke. We also assessed the risks
of CHD stratified by gender, age group (<35, 35–49, 50–64,
65–79 and ≥ 80 years) or comorbidities including hypertension,
diabetes, hyperlipidaemia and stroke. Additionally, there were
four separate models (hypertension, diabetic mellitus, hyperlip-
idaemia and stroke) stratified by COM to assess the joint effects
on the risk of CHD. For example, the hypertension group
included hypertension patients with or without any other
comorbidity, and those with only other comorbidities were
excluded from that particular model. Furthermore, the associ-
ation between the risk for CHD and the severity of COM was
examined. The osteomyelitis severity was defined as the division
of total length of hospital stay due to COM during the
follow-up duration by the length of follow-up duration. By
using the tertile method, the severity of COM was further classi-
fied into three levels: mild (the first tertile), moderate (the
second tertile) and severe (the third tertile). Kaplan–Meier
model was used to describe the disease-free rate curve and
log-rank test used to test the difference between case and
control cohorts.
RESULTS
All 15 054 patients with osteomyelitis and 60 216 controls were
selected in the present study. The mean age was 54.0 years (SD
19.1) and men were the majority (66.4% vs 33.6%) in patients
with osteomyelitis. Compared with controls, patients with
osteomyelitis had higher percentages of hypertension, diabetes
mellitus, hyperlipidaemia and stroke, as shown in table 1.
During a follow-up period of 67 927 person-years, the overall
incidence rate of CHD in osteomyelitis cohort was 1.95 times
higher than non-osteomyelitis cohort (16.66 vs 8.52 per 1000
person-years, table 2). After controlling age, gender and four
comorbidities, the risk remained significantly higher in the
COM cohort than the control group (adjusted HR (aHR)
=1.65, 95% CI=1.54 to 1.78, p<0.001, model 2 in table 2).
Regardless of female or male, the risks of CHD in the COM
group were significantly increased when compared with the
control group (both p<0.001, table 2). The incidence of CHD
rose from 1.19 to 50.4 and 0.22 to 32.20 per 1000 person-
years with increasing age in osteomyelitis and non-osteomyelitis
cohort, respectively. It is worth to be highlighted that in
age-stratification analysis, the highest risk was in the youngest
age group and the HR declined from 3.42 to 1.39 with advan-
cing age. The Kaplan–Meier analysis reveals that during a
follow-up of 10 years, the CHD-free survival rate in patients
with osteomyelitis was significantly lower than the control
group (log-rank p<0.0001).
Table 3 shows the incidence and HRs for CHD, stratified by
comorbidity. The incidence of CHD in study subjects with any
comorbidity was 5.16-fold higher than those without any
comorbidity (33.97 vs 6.58 per 1000 person-years, data not
shown). Among subjects with comorbidity, the risk in patients
with osteomyelitis was significantly elevated in comparison with
controls (aHR=1.57, 95% CI 1.42 to 1.73, p<0.001, model 1
in table 3). In comorbidity stratification analysis, COM cohort
was at a significantly higher risk of developing CHD in the pres-
ence of hypertension (aHR=1.41, 95% CI 1.24 to 1.59,
p<0.001), diabetes mellitus (aHR=1.47, 95% CI 1.28 to 1.69,
p<0.001) or stroke (aHR=1.54, 95% CI 1.28 to 1.87,
p<0.001), respectively (model 2 in table 3). Further, in the
absence of any comorbidity such as hypertension, diabetes,
hyperlipidaemia and stroke, the risk of CHD development was
still statistically higher in the COM cohort (adjusted for age and
Table 1 Comparison of demographics between chronic
osteomyelitis and non- osteomyelitis groups
Non-COM
N=60 216
COM
N=15 054
Variable N Per cent n Per cent
Gender
Women 20 228 33.6 5057 33.6
Men 39 988 66.4 9997 66.4
Age, years
<35 10 944 18.1 2736 18.1
35–49 13 668 22.7 3417 22.7
50–64 15 556 25.8 3889 25.8
65–79 15 576 25.9 3894 25.9
≥80 4472 7.43 1118 7.43
Comorbidity
Hypertension 5125 8.51 3374 22.4
Diabetes mellitus 2830 4.70 3354 22.3
Hyperlipidaemia 924 1.53 734 4.88
Stroke 2365 3.93 1367 9.08
COM, chronic osteomyelitis.
2 Hsiao L-C, et al. Heart 2014;0:1–5. doi:10.1136/heartjnl-2014-305652
Coronary artery disease
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gender, aHR=1.60, 95% CI 1.44 to 1.79, p<0.001, model 1 in
table 3).
The joint effects of COM combined with any of the four
comorbidities on CHD risk are presented in table 4. In osteo-
myelitis population, patients with hyperlipidaemia had the
highest risk of CHD (aHR=3.59, 95% CI 2.89 to 4.46) com-
pared with those without any comorbidity, and followed by
those with diabetes mellitus (aHR=3.50, 95% CI 2.89 to 4.46),
hypertension (aHR=2.79, 95% CI 2.42 to 3.22) and stroke
(aHR=2.58, 95% CI 2.13 to 3.11). The control group followed
the same trend of effects. The association between the risk of
CHD and severity of osteomyelitis was shown in table 5.
Compared with the control group, the risk was increased with
severity (mild: aHR=0.95, 95% CI 0.85 to 1.06; moderate:
aHR=1.88, 95% CI 1.68 to 2.11; severe: aHR=5.36, 95% CI
4.78 to 6.01, trend test p<0.0001).
DISCUSSION
It has been observed that approximately 10–50% of people
developed CHD without classical risk factors.
3821–23
As a
result, a number of other possible risk factors have been pro-
posed to explain the discrepancy, including infection, inflamma-
tion, excessive oxidative stress and homocysteinemia.
317
It has
been postulated that these novel risk factors cause atheroscler-
osis likely through triggering of endothelial injury (endothelial
dysfunction), followed by intimal thickening, plaque formation
Table 2 Incidence and HR for coronary heart disease between chronic osteomyelitis and non-osteomyelitis groups by stratified demographics
COM Compared with non-COM, HR (95% CI)
No Yes
Variable Case P-Y IR Case P-Y IR Crude Model 1 Model 2
Overall 2658 311 893 8.52 1132 67 927 16.66 1.95 (1.82 to 2.09)*** 2.15 (2.00 to 2.30)*** 1.65 (1.54 to 1.78)***
Gender
Female 959 103 220 9.29 413 22 506 18.35 1.97 (1.75 to 2.21)*** 2.11 (1.88 to 2.37)*** 1.60 (1.42 to 1.81)***
Male 1699 208 673 8.14 719 45 422 15.83 1.94 (1.78 to 2.12)*** 2.17 (1.90 to 2.37)*** 1.68 (1.53 to 1.84)***
Age, years
<35 14 64 133 0.22 19 16 033 1.19 5.44 (2.73 to 10.9)*** 5.44 (2.73 to 10.8)*** 3.42 (1.60 to 7.32)**
35–49 177 76 295 2.32 135 17 239 7.83 3.40 (2.72 to 4.26)*** 3.42 (2.73 to 4.28)*** 2.02 (1.56 to 2.62)***
50–64 556 81 716 6.80 331 17 451 18.97 2.80 (2.44 to 3.20)*** 2.81 (2.45 to 3.22)*** 1.66 (1.42 to 1.93)***
65–79 1405 74 035 18.98 507 14 428 35.14 1.86 (1.68 to 2.06)*** 1.87 (1.69 to 2.07)*** 1.47 (1.32 to 1.63)***
≥80 506 15 715 32.20 140 2777 50.42 1.56 (1.29 to 1.88)*** 1.56 (1.29 to 1.88)*** 1.39 (1.15 to 1.68)***
Incidence rate, per 1000 person-years.
Crude, crude HR without adjustment.
Model 1, mutually adjusted for age and gender.
Model 2, mutually adjusted for age, gender, hypertension, diabetes, hyperlipidaemia and stroke in Cox proportional hazards regression.
**p<0.01, ***p<0.001.
COM, chronic osteomyelitis; P-Y, person-years; IR, incidence rate.
Table 3 Incidence and HR for coronary heart disease between chronic osteomyelitis and non-osteomyelitis groups by stratified comorbidities
COM Compared with non-COM, HR (95% CI)
No Yes
Comorbidity Case P-Y IR Case P-Y IR Crude Model 1 Model 2
Without 1791 283 531 6.32 399 49 191 8.11 1.28 (1.15 to 1.43)*** 1.60 (1.44 to 1.79)***
With 867 28 363 30.57 733 18 737 39.12 1.28 (1.16 to 1.41)*** 1.57 (1.42 to 1.73)***
Hypertension
No 2016 292 497 6.89 656 57 188 11.47 1.66 (1.52 to 1.82)*** 1.99 (1.82 to 2.17)*** 1.68 (1.53 to 1.84)***
Yes 642 19 396 33.1 476 10 739 44.32 1.34 (1.19 to 1.50)*** 1.54 (1.37 to 1.74)*** 1.41 (1.24 to 1.59)***
Diabetes mellitus
No 2272 301 197 7.54 622 56 454 11.02 1.46 (1.34 to 1.60)*** 1.69 (1.55 to 1.85)*** 1.57 (1.43 to 1.72)***
Yes 386 10 696 36.09 510 11 473 44.45 1.23 (1.08 to 1.40)** 1.48 (1.29 to 1.70)*** 1.47 (1.28 to 1.69)***
Hyperlipidaemia
No 2532 308 173 8.22 1027 65 466 15.69 1.90 (1.77 to 2.05)*** 2.10 (1.96 to 2.26)*** 1.66 (1.54 to 1.80)***
Yes 126 3721 33.87 105 2462 42.65 1.25 (0.97 to 1.62) 1.55 (1.19 to 2.03)** 1.29 (0.98 to 1.70)
Stroke
No 2365 303 165 7.80 949 64 154 14.79 1.89 (1.76 to 2.04)*** 2.13 (1.98 to 2.30)*** 1.64 (1.52 to 1.78)***
Yes 293 8728 33.57 183 3773 48.50 1.45 (1.20 to 1.74)*** 1.68 (1.39 to 2.02)*** 1.54 (1.28 to 1.87)***
Incidence rate, per 1,000 person-years.
Crude, crude HR without adjustment.
Model 1, mutually adjusted for age and gender.
Model 2, mutually adjusted for age, gender, hypertension, diabetes, hyperlipidaemia and stroke in Cox proportional hazards regression.
**p<0.01, ***p<0.001.
COM, chronic osteomyelitis; P-Y person-years; IR, incidence rate.
Hsiao L-C, et al. Heart 2014;0:1–5. doi:10.1136/heartjnl-2014-305652 3
Coronary artery disease
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and eventual disruption of vulnerable plaque.
32425
To the best
of our knowledge, this is the first report of the association
between COM and CHD using a nationwide population-based
dataset. In this study, we discovered a significantly higher risk
(1.65-fold) of developing CHD among patients with COM
during a long-term follow-up period. According to our findings,
patients with COM of ≥35 years of age had a 4% increased risk
for CHD with 1-year increase in age.
With the introduction of stratification analyses, the incidence
and risk of CHD significantly increased with age in both COM
and non-COM groups and among patients with any of four
comorbidities. These findings are generally in line with previous
studies, attesting the reliability of our dataset. More importantly,
our data also demonstrate that COM was associated with a
higher risk of developing CHD, either with or without any of
other traditional risk factors, including hypertension, diabetes
mellitus, hyperlipidaemia and stroke. The combination of COM
and these conventional risk factors further enhance the risk of
CHD, especially in the group of COM and hyperlipidaemia,
which carries the highest risk for CHD development
(aHR=3.59, 95% CI 2.89 to 4.46).
An interestingly inverse relationship between CHD risk and
the advancement of age was observed in COM cases (from
aHR=3.42, 95% CI 1.60 to 7.32 in age <35 to aHR=1.39,
95% CI 1.15 to 1.68 in age ≥80). Although the statistics of
strong association between COM and CHD risk in the lowest
age group might be affected by a small number of people
enrolled, a consistent inverse relationship between CHD risk
and increasing age still remains in other age groups. We believe
that the relatively stronger association between COM and CHD
in younger population may be attributable to less traditional risk
factors in the these patients compared with the elderly, which in
turn contributes to a greater association of COM with the CHD
risk in younger patients. This finding carries an important impli-
cation for clinical practice in real world. Indeed, further studies
are necessary to explore the underlying mechanisms linking
COM and CHD.
For a long time, it has been thought that CHD mainly results
from coronary atherosclerosis due to cholesterol deposition in
coronary arteries.
14
With time, nevertheless, the concept of the
pathophysiology of CHD has been linked to a chronic dynamic
inflammatory process, associated with the interaction between
immune response and lipid deposition.
3
The role of infection in
the trigger and progression of atherosclerosis has attracted con-
siderable attention in recent years since chronic infection may
lead to a chronic inflammatory reaction in the body.
17
A
number of infectious pathogens, including herpes simplex virus,
cytomegalovirus, HIV, Chlamydia pneumonia and Helicobacter
pylori, have been found to be linked to atherosclerosis.
326–28
With accumulating evidence, it has been proposed that patients
with chronic inflammatory disorders are at increased risk of
CHD.
24
Patients with COM, with a difficulty in eradication of
bacterial pathogen hiding in bone and surrounding soft tissue,
may be embedded in a long-term inflammatory state that might
increase the risk of CHD.
29
This study has several advantages in terms of study design
and statistics. First, it should be highlighted that this research
was conducted on the basis of a nationwide population-based
dataset consisting of more than 98% of the entire population in
Taiwan. Insurance claims for expenditure of in-hospital manage-
ment have been strictly monitored and audited by NIH to avoid
healthcare frauds. The stringent surveillance programme con-
firms the reliability of the diagnosis.
20
Second, the large sample
size, including 15 054 osteomyelitis patients and 60 216 age-
matched and gender-matched controls, improves the validity of
data and provides adequate power to find a reliable statistical
significance. The demographic profile reveals gender difference
and unique age distribution, which is consistent with the previ-
ous studies, all attesting the reliability of this dataset.
30
Collectively, these strengths allow us to discover a linkage
between presence of COM and increased risk of CHD, as
shown in this study.
Study limitations
However, there are still some limitations in the current study.
First, we could not exclude the possibility of other coexistent
vascular risk factors, such as altered immunity, reduced physical
activities and medications for COM, which might also predis-
pose patients to increased CHD risk. Thus, the CHD risks
derived from the present study may carry superimposed factors
on COM. Second, the personal health habits, such as smoking
and alcohol consumption, were not available in the Taiwan NHI
dataset for evaluating their association with the increased risk of
CHD in patients with COM. However, given that COM
increased CHD risk in both genders and there is a very low
smoking rate (<3%) among females in Taiwan, this indicates
that smoking is unlikely to be a confounding variable for the
significant increase in CHD risk in patients with COM. Finally,
we have noted that there are relatively high prevalence rates of
comorbidities among patients with COM compared with con-
trols. However, our results show that even among those without
CHD-related comorbidities, presence of COM was still highly
Table 4 Joint effects of associated comorbidities on chronic
osteomyelitis and non-osteomyelitis for coronary heart disease
COM Non-COM
Comorbidity Case
Adjusted
HR (95% CI) Case
Adjusted
HR (95% CI)
None 399 1.00 1791 1.00
With hypertension 476 2.79 (2.42 to 3.22)*** 642 2.25 (2.04 to 2.47)***
With diabetes
mellitus
510 3.50 (3.06 to 4.00)*** 386 2.76 (2.47 to 3.10)***
With
hyperlipidaemia
105 3.59 (2.89 to 4.46)*** 126 3.06 (2.55 to 3.67)***
With stroke 183 2.58 (2.13 to 3.11)*** 293 2.06 (1.81 to 2.34)***
Adjusted for age and gender.
***p<0.001.
p>0.05 in all interaction.
COM, chronic osteomyelitis.
Table 5 Incidence and HR for coronary heart disease stratified by
the severity of chronic osteomyelitis
COM severity Event P-Y IR Adjusted HR (95% CI)
Compared group 2658 311 893 8.52 1.00
Mild (T1) 376 44 309 8.49 0.95 (0.85 to 1.06)
Moderate (T2) 363 18 088 20.07 1.88 (1.68 to 2.11)***
Severe (T3) 393 5530 71.06 5.36 (4.78 to 6.01)***
p for trend <0.0001
Incidence rate, per 1000 person-years.
COM severity=(total length of hospital stay due to chronic osteomyelitis during the
follow-up duration) ÷ (length of follow-up duration).
Adjusted HR, adjusted for age, gender, hypertension, diabetes, hyperlipidaemia and
stroke in Cox proportional hazards regression.
*** p<0.001.
COM, chronic osteomyelitis; P-Y, person-years; IR, incidence rate; T1, first tertile; T2,
second tertile; T3, third tertile.
4 Hsiao L-C, et al. Heart 2014;0:1–5. doi:10.1136/heartjnl-2014-305652
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associated with CHD. The time-dependent and severity-
dependent effects of COM on CHD risk also demonstrate a
consistent finding that COM was associated with a higher risk
on the development of CHD.
CONCLUSION
This is the first study showing that COM is associated with the
development of CHD, especially in the younger age group. It is
believed that this implication has paved the way for further
exploration in the pathogenesis, risk prediction and treatment
of COM in relation to CHD prevention in the future.
Key messages
What is known on this subject?
▸ Although a number of traditional risk factors have been
identified in the development of coronary heart disease
(CHD), suc h as hypertension, hyperlipidaemia and type 2
DM, it has been observed that about 10–50% of people
developed CHD without these classical risk factors.
▸ Infection and inflammation have been proposed as novel risk
factors in atherosclerotic disease.
What might this study add?
▸ Chronic osteomyelitis (COM), a long-term infection of bone
and bone marrow, could lead to a subsequent chronic
inflammatory process in the body.
▸ To improve CHD prevention and management, it would be
important to understand whether COM serves as a novel risk
factor in the development of CHD.
How might this impact on clinical practice?
▸ Results presented in this study suggest that COM is a risk
factor for CHD, independent of age, gender, hypertension,
diabetes, hyperlipidaemia and stroke.
▸ This implication has paved the way for further exploration in
the pathogenesis, risk prediction and treatment of COM in
relation to CHD prevention in the future.
Acknowledgements The authors thank the National Health Research Institute in
Taiwan for making insurance claims data available for medical analyses.
Contributors K-CC, L-CH and C-HT designed research; C-HM, Y-CC, C-YC and
L-CH analysed the data; L-CH and K-CC wrote the paper.
Funding This study was supported in part by the National Science Council, Taiwan
(NSC 100-2314-B-039-042, NSC 101-2314-B-039-039 and NSC
102-2314-B-039-019), Taiwan Department of Health Clinical Trial and Research
Center for Excellence (DOH102-TD-B-111-004), Taiwan Department of Health
Cancer Research Center for Excellence (DOH102-TD-C-111-005) and China Medical
University Hospital (DMR-101-006, DMR-102-007 and DMR-103-003). All of the
aforementioned funding sources had no further role in study design; in the
collection, analysis and interpretation of data; in the writing of the report; or in the
decision to submit the paper for publication.
Competing interests None.
Ethics approval IRB at the China Medical University Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
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Hsiao L-C, et al. Heart 2014;0:1–5. doi:10.1136/heartjnl-2014-305652 5
Coronary artery disease
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published online June 4, 2014Heart
Lien-Cheng Hsiao, Chih-Hsin Muo, Yu-Ching Chen, et al.
million
population-based study in a cohort of 23
patients with chronic osteomyelitis: a
Increased risk of coronary heart disease in
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