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JACC VOL. 65, NO. 24, 2015
Letters
JUNE 23, 2015:2667–76
T A B L E 1 ANA Associations With Mortality Outcomes and Cardiovascular Events
Events (n)
Unadjusted
HR (95% CI)
Model 1
HR (95% CI)
Model 2
HR (95% CI)
158
1.29 (1.13–1.48)
1.27 (1.10–1.46)
1.26 (1.10–1.46)
0.0002
0.0008
0.002
54
1.45 (1.17–1.79)
1.42 (1.13–1.77)
1.37 (1.10–1.73)
0.0006
0.002
0.01
157
1.16 (1.01–1.35)
1.17 (1.01–1.35)
1.18 (1.01–1.37)
0.04
0.04
0.04
All-cause mortality
p Value
Cardiovascular death
p Value
ASCVD
p Value
Sensitivity Analysis in Participants With ANA <65 EU
All-cause mortality
145
1.31 (1.07–1.61)
1.28 (1.03–1.58)
0.01
0.02
0.047
50
1.69 (1.19–2.40)
1.62 (1.13–2.30)
1.49 (1.02–2.17)
0.003
0.009
0.04
148
1.22 (0.99–1.50)
1.23 (1.0–1.51)
1.22 (0.98–1.51)
0.058
0.054
0.07
p Value
Cardiovascular death
p Value
ASCVD
p Value
1.25 (1.002–1.56)
N ¼ 2,803. Hazard ratios (HRs) and 95% confidence intervals (CIs) for 1 SD increase in log (ANA).
ANA ¼ antinuclear autoantibodies; ASCVD ¼ atherosclerotic cardiovascular disease; EU ¼ enzyme-linked immunosorbent assay unit(s).
general population. In contrast, our study represents
a population-based assessment of the implications of
low-level ANA.
The DHS is an observational cohort; thus, we
cannot determine whether the association between
ANA and adverse events is causal. These findings
raise the possibility that the presence of ANA signals
immunological events that are affecting vascular
health, although the exact role requires further study.
Several study limitations are noteworthy. Baseline
ANA were performed; thus, we cannot account for variability in ANA or autoimmunity over time. Exclusion
of participants with autoimmune disease was on the
basis of self-report, rather than physician evaluation.
In conclusion, increasing ANA are independently
associated with all-cause mortality, cardiovascular
death, and ASCVD in a representative multiethnic
population-based cohort. ANA may identify individuals at increased risk of death and ASCVD
independent of traditional risk factors or clinical
autoimmune disease, a finding that potentially
affects a substantial percent of the population.
*Elizabeth Blair Solow, MD
Wanpen Vongpatanasin, MD
Brian Skaug, MD
David R. Karp, MD, PhD
Colby Ayers, MS
James A. de Lemos, MD
*Division of Rheumatic Diseases
Please note: The Dallas Heart Study was funded by the Donald W. Reynolds
Foundation and was partially supported by the National Center for Advancing
Translational Sciences of the National Institutes of Health (NIH) under award
number UL1TR001105. Dr. Solow has received research support from the American Heart Association, National Center for Advancing Translational Sciences of
the NIH, and Bristol-Myers Squibb. Dr. Vongpatanasin has received support from
University of Texas Southwestern O’Brien Kidney Center P30 DK079328. Dr. Karp
receives support from NIH P50 AR055503. Dr. de Lemos has received grant support and consulting income from Roche Diagnostics and Abbott Diagnostics; and
has served as a consultant for Diadexus. Dr. Skaug and Mr. Ayers have reported
that they have no relationships relevant to the contents of this paper to disclose.
REFERENCES
1. Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of
myocardial infarction and angina in women with systemic lupus erythematosus:
comparison with the Framingham Study. Am J Epidemiol 1997;145:408–15.
2. Wandstrat AE, Carr-Johnson F, Branch V, et al. Autoantibody profiling to
identify individuals at risk for systemic lupus erythematosus. J Autoimmun
2006;27:153–60.
3. de Lemos JA, Drazner MH, Omland T, et al. Association of troponin T
detected with a highly sensitive assay and cardiac structure and mortality risk
in the general population. JAMA 2010;304:2503–12.
4. Pertovaara M, Kahonen M, Juonala M, et al. Autoimmunity and atherosclerosis: the presence of antinuclear antibodies is associated with decreased
carotid elasticity in young women. The Cardiovascular Risk in Young Finns
Study. Rheumatology (Oxford) 2009;48:1553–6.
5. Liang KP, Kremers HM, Crowson CS, et al. Autoantibodies and the risk of
cardiovascular events. J Rheumatol 2009;36:2462–9.
Light and Moderate
Joggers Do Not Have
Lower Mortality Rates
Than Strenuous Joggers
University of Texas Southwestern
5323 Harry Hines Boulevard
The recently published paper by Schnohr et al. (1) on
Dallas, Texas 75390-8884
jogging and long-term mortality concluded that there
E-mail: [email protected]
was a U-shaped association between all-cause mor-
http://dx.doi.org/10.1016/j.jacc.2015.03.578
tality and dose of jogging, and that low-intensity
JACC VOL. 65, NO. 24, 2015
Letters
JUNE 23, 2015:2667–76
jogging was more beneficial than high-intensity
jogging. However, this conclusion cannot be drawn
Please note: Dr. Anderson has reported that he has no relationships relevant to
the contents of this paper to disclose.
from the data presented.
Schnohr et al. claim to have analyzed the quantity,
frequency, and pace of jogging. However, only frequency was assessed, and instead of quantity and pace,
they assessed time spent jogging and perceived intensity, respectively. A fit person may cover a much
longer distance during the same time as an unfit person
and perceive the same absolute intensity as light
instead of strenuous. This is a serious problem, because
cardiorespiratory fitness is strongly related to mortality
REFERENCE
1. Schnohr P, O’Keefe JH, Marott JL, Lange P, Jensen GB. Dose of jogging and
long-term mortality: the Copenhagen City Heart Study. J Am Coll Cardiol
2015;65:411–9.
2. Schnohr P, Scharling H, Jensen JS. Intensity versus duration of walking,
impact on mortality: the Copenhagen City Heart Study. Eur J Cardiovasc Prev
Rehabil 2007;14:72–8.
3. Schnohr P, Marott JL, Jensen JS, Jensen GB. Intensity versus duration of
cycling, impact on all-cause and coronary heart disease mortality: the
Copenhagen City Heart Study. Eur J Cardiovasc Prev Rehabil 2012;19:73–80.
and to the analyzed exposures. This confounding was
not taken into account, and adjustment for fitness
could have resulted in the opposite conclusion.
None of the conclusions are justified by the
statistical analysis. In the analysis of the 3 exposures—
Absolute or Relative
Jogging Pace
What Makes the Difference?
quantity, frequency, and pace of jogging—the confidence intervals of the subgroups overlap, which
means there are no differences between the groups.
We appreciate the findings reported by Schnohr et al.
Most of the subgroups include only 1 to 5 cases, and
(1), but we feel that insufficient attention has been
the conclusions based on this few cases cannot be
paid to the consequences of pace categorization
justified. An analysis in which all of the jogging groups
by self-reporting. The investigators demonstrate a
are merged could make statistical sense, and it could
U-shaped relationship between the dose of jogging
conclude that there is a substantial benefit to jogging,
and all-cause mortality. Joggers were categorized as
but not how fast, how long, or how frequently jogging
light, moderate, or strenuous joggers on the basis of
should take place.
the quantity of jogging and the self-reported pace
The investigators concluded that there is a U-shape
(slow, average, fast). The use of the self-reported
between the dose of jogging and mortality. The defi-
(perceived) pace makes sense from a practical and
nition of what is light, moderate, and strenuous
clinical point of view, but it is unjustified to assign
jogging is problematic, because the study did not
fixed amounts of miles per hour to the pace cate-
assess these exposures, as previously mentioned. The
gories without considering individual fitness levels.
strenuous group experienced only 2 deaths, and to
Everybody will agree that a pace of 7 mph will
draw conclusions of a U-shape on the basis of 2 cases
generate different cardiovascular responses and will
cannot be justified. The investigators do not describe
be perceived differently by a 35-year-old elite runner
how the 413 joggers in the reference group were
than an 85-year-old amateur runner due to the huge
selected from among the 3,950 nonjoggers, but it
differences in aerobic power (cardiovascular fitness)
is obvious that an age difference of approximately
(2). Thus, the U-shaped association between the dose
20 years between the reference group and all sub-
of jogging and mortality is likely to be true when
groups of joggers points to a severe selection bias,
based on the individually perceived pace, but is very
which makes a comparison difficult.
likely wrong when based on absolute values. In our
Finally, it is surprising that the investigators did
opinion, this is a critical point, because a pace of 7
not discuss in detail why 2 recently published studies
mph is fast for a novice or an amateur runner but is a
that analyzed walking (2) and cycling (3) from the
perceived slower pace for an elite runner. Profes-
same data came up with the opposite conclusion in
sional endurance athletes usually perform >80% of
relation to intensity and duration of physical activity.
their training sessions at light intensities (50% to
70% of their maximal heart rate) (3), and therefore,
*Lars Bo Andersen, Dr Med Sci
would be rated as moderate or even light joggers
*Department of Sport Science and Clinical Biomechanics
according to the categorization applied by Schnohr
University of Southern Denmark
et al. (1). This is compared with novice runners who
Campusvej 55, Odense 5230
often train at too high intensities. Furthermore,
Denmark
numerous middle-aged and poorly prepared recrea-
E-mail: [email protected]
tional runners start strenuous running programs af-
http://dx.doi.org/10.1016/j.jacc.2015.02.079
ter cardiovascular disease diagnosis. This means that
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