Relation of Serum Lactate Dehydrogenase to Coronary Artery

Disease
Eran Kopel, MDa,b,*,†, Shaye Kivity, MDa,c,d,e,†, Nira Morag-Koren, PhDf, Shlomo Segev, MDg, and
Yechezkel Sidi, MDa,e
Serum lactate dehydrogenase (LDH) is known pathologic marker for a diversity of diseases,
including myocardial ischemia. Strenuous and enduring physical activity can transiently
induce a greater total LDH level, still within its normal range. To date, however, it has not
been determined whether normal-range LDH might be inversely associated with coronary
artery disease (CAD) in the low-cardiovascular-risk, physically active, adult population.
We conducted a retrospective cohort analysis. A total of 5,519 healthy adults aged 34 to 86
years were followed up for a mean period of 4.2 years. The cohort incidence of CAD was
6.1% (338 cases) from 2001 to 2009. In the present cohort, greater mean LDH levels were
significantly associated with a greater number of years, days/week, and minutes/week of
leisure time activity (p ⴝ 0.02, p ⴝ 0.04, and p ⴝ 0.01, respectively). These associations
were externally validated successfully by analysis of all 5,064 healthy participants aged
>40 years with normal-range LDH from the 2007 to 2010 National Health and Nutrition
Examination Surveys combined. For instance, the mean LDH level was significantly
greater in those engaged in 6 to 7 versus 1 to 5 days/wk of vigorous-intensity work activity
(138.0 ⴞ 20.7 IU/L vs 133.3 ⴞ 21.7 IU/L, respectively, p ⴝ 0.007). In our cohort, the hazard
ratio for CAD according to the normal total serum LDH tertiles, adjusted for multiple risk
and protective CAD factors in a Cox proportional hazards model, was 0.70 (95% confi-
dence interval 0.54 to 0.92) in the greater versus lower tertile (p for trend ⴝ 0.01). In
conclusion, we suggest that increased normal-range total serum LDH is associated with
reduced short-term risk of CAD outcome in this low-risk, physically active
population. © 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:1717–1722)

Lactate dehydrogenase (LDH) is a cytoplasmic enzyme
found in all body cells that catalyzes the reversible conver-
sion of pyruvate, the primary end-product of glycolysis, to
lactate as a part of the lactic acid (Cori) cycle. This meta-
bolic pathway is accelerated under anaerobic physiologic
conditions such as during increased power output of skeletal
muscle activity. Using the cell-to-cell lactate shuttle and
their tissue-specific LDH isoenzyme, both skeletal and car-
diac muscles avidly oxidize lactate as a fuel, accounting for
ⱕ60% of the energy supply in the myocardium.1–3 Physical
activity can immediately and transiently induce between
minimal, nonsignificant, and ⱕ25% elevation of total serum
a
Departments of Internal Medicine C and cInternal Medicine A;
d
Center of Autoimmune Diseases, and gInstitute of Preventive Medicine,
Chaim Sheba Medical Center, Tel Hashomer, Israel; bTel Aviv District
Health Office, Ministry of Health, Tel Aviv, Israel; eSackler School of
Medicine, Tel Aviv University, Tel Aviv, Israel; and fDepartment of
Epidemiology and Preventive Medicine, Sackler School of Medicine, Tel
Aviv University, Tel Aviv, Israel. Manuscript received June 19, 2012;
revised manuscript received and accepted August 8, 2012.
This work was supported by the Shalvi Foundation for Medical Re-
search.
The sponsor had no role in designing or conducting the study and no
role in gathering or analyzing the data or writing the manuscript.
*Corresponding author: Tel: ⫹972-3-530-2464; fax: ⫹972-3-530-
2011.
E-mail address: eran.kopel@mail.huji.ac.il (E. Kopel).
†
Drs. Kopel and Kivity contributed equally to this article.
LDH after the most strenuous and enduring types of exer-
cise, but still within the normal laboratory values.1,4 –7 Ab-
normal serum LDH levels, greater than the upper laboratory
limit, is a nonspecific, clinical, pathologic marker of many
medical conditions, including myocardial ischemia,8 muscle
injury,9 hemolysis,10 and malignant melanoma.11 We won-
dered whether, because it is related to strenuous physical
activity and reversible ischemic conditions, all within the
normal body physiology, normal-range LDH could be in-
versely associated with coronary artery disease (CAD) in
the low-risk, physically active, ambulatory adult population.
To test this a priori hypothesis, we conducted a retrospective
cohort analysis of a highly selected, healthy, ambulatory
population.
Methods
The Executive Screening Survey performs annual
screening examinations of apparently healthy adult men and
women of the general ambulatory population at the Chaim
Sheba Medical Center (Tel Hashomer, Israel). The full
methods used by this routine program have been previously
published.12 The computerized database, established in
2000, was the data source for the present study.
Included in the present retrospective analysis of this
convenience sample were all men and women, aged ⬎34
years, who met all the following criteria at baseline: (1) no
history of type 1 or 2 diabetes mellitus; (2) no history of
heart, cardiovascular, cerebrovascular, or vascular illness, in

0002-9149/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved. www.ajconline.org
http://dx.doi.org/10.1016/j.amjcard.2012.08.005
1718 The American Journal of Cardiology (www.ajconline.org)
particular, CAD, congestive heart failure, arrhythmia, val-
vular heart disease, ischemic cerebral stroke, peripheral
vascular disease, or hypertension; (3) no history of hyper-
lipidemia; (4) not taking permanent medications; (5) mea-
sured serum LDH value at baseline within the normal range
of the medical center’s central laboratory (100 to 260 IU/L
during the entire study period); (6) a record of ⱖ1 follow-up
visit that was ⱖ1 year apart from the baseline visit; and (7)
complete demographic data (age and gender). The final
retrospective cohort included 5,519 apparently healthy am-
bulatory persons with a relatively low risk of cardiovascular
disease, who were followed up from May 2001 to December
2009.
We defined a composite study end point of the time-to-
event of any of the following events: (1) newly diagnosed
CAD (the main morbidity outcome measure, as detailed in
the following section); (2) new cerebrovascular accident or
transient ischemic attack, as determined by a documented
neurologic deficit; and (3) new-onset type 1 or 2 diabetes
mellitus diagnosed by 2 consecutive fasting glucose tests
⬎125 mg/dl performed at the examination center or diag-
nosed in the community and reported by the subject at any
annual follow-up visit.
The main outcome measure (dependent variable) was the
diagnosis of new-onset CAD. The outcome was concluded
if the subject presented, at any annual follow-up visit, with
documented new CAD. This was determined if the subject
had presented with angiography proven stenosis ⬎50% in
ⱖ1 coronary artery, positive perfusion thallium-201 scin-
tigraphy findings, or positive ergometry test using the Bruce
protocol.13 Examinees with pathologic ergometry or thalli-
um-201 scintigraphy results were usually referred for cor-
onary angiography.
The 2 other major disease outcomes, cerebrovascular
disease and diabetes mellitus, also prevalent in the adult
population, were used for censoring, if either appeared be-
fore the development of CAD, to avoid their potential effect
on a future co-morbid CAD diagnosis. This could occur
with the greater frequency of medical follow-up visits for
already morbid subjects (surveillance bias) or because both
the LDH level and the CAD outcome might be affected in
various ways by these systemic co-morbidities (confound-
ing bias).
All the independent variables, including those deter-
mined from the blood samples, were measured or deter-
mined at baseline. Blood samples were obtained in the
morning after a 12-hour nocturnal fast and before the exer-
cise test. The age-predicted maximal heart rate-percentage
(APMHR%) was calculated as the percentage of the age-
predicted maximal heart rate (defined by the formula [220
⫺ age]) achieved during ergometry test. The ergometry
fitness level was categorized according to standard gender-
adjusted categories of the routinely calculated maximal ox-
ygen uptake, using the Bruce protocol.13 Regular leisure
time physical activity as a dichotomous variable was de-
fined as reporting regular engagement in ⱖ1 specific leisure
time activity, such as walking or jogging. The baseline body
mass index was calculated using the formula, weight in
kilograms divided by the height in square meters. A family
history of cardiovascular disease was defined as reporting
CAD in a first-degree relative.
The United States National Health and Nutrition Exam-
ination Surveys (NHANES) of 2005 to 2006, 2007 to 2008,
and 2009 to 2010 were combined for the purpose of external
cross-sectional validation and examination of possible as-
sociations between normal LDH levels and physical activity
or alcohol consumption characteristics in a large represen-
tative sample of the general ambulatory population. The
NHANES is a routine, nationwide program of studies that
includes personal interviews, physical examinations, and
various laboratory tests.14
We included in the analysis all NHANES 2005 to 2010
participants aged ⱖ40 years (a blood sample for LDH was
only drawn from those aged ⱖ40 years), who reported no
history of coronary heart disease, heart attack, diabetes or
borderline/prediabetes, or stroke, and had normal LDH lev-
els (range 93 to 198 IU/L, inclusive in all 3 NHANES
surveys) at the survey. For the analysis of various physical
activity characteristics, we included the participants of
the 2007 to 2010 surveys only, because the different set
of physical activity questions used in the NHANES 2005
to 2006 survey.
The frequencies and percentages were calculated for the
categorical variables, and the mean ⫾ SD for continuous
variables. For the triglycerides levels, the median and inter-
quartile range were also calculated. In the univariate anal-
ysis of baseline characteristics, the chi-square test, with
continuity correction for 2 ⫻ 2 tables in the case of dichot-
omous variables, was used to measure the significance of
categorical variable associations with the main dichotomous
outcome measure (CAD). The Student t test was used to
measure the significance of the mean differences of the
continuous variables with the CAD outcome and to measure
the differences in mean continuous LDH levels across the
physical activity characteristics, dichotomized. One-way
analysis of variance was used to test the differences in the
mean continuous LDH levels across physical activity or
alcohol consumption characteristics of ⬎2 groups. The
baseline categorical independent variables and the incidence
of CAD were analyzed for the significance of trends across
the normal-range LDH tertiles using the chi-square linear-
by-linear association test or the nonparametric Kruskal-
Wallis 1-way analysis of variance test for baseline contin-
uous variables.
We used multivariate Cox proportional hazards anal-
ysis to estimate the hazard ratio (HR) and 95% confi-
dence interval for having the CAD outcome according to
the tertiles of normal-range LDH. The proportional haz-
ards assumptions were evaluated using log-minus-log
plots. The models were adjusted for variables that had a
significant association with CAD outcome on univariate
analysis or if they were a previously known risk, or
protective, factor for CAD. The significance of trend
between HRs of LDH tertiles was measured as the overall
given p value of the LDH tertiles’ variable within each
model. All p value calculations were 2-tailed and were
considered statistically significant if their value was p
⬍0.05. The statistical analyses were performed with IBM
SPSS, version 19.0 (IBM, SPSS, Chicago, Illinois). The
institutional review board approved the present study.
 Coronary Artery Disease/LDH and CAD 1719

Table 1
Baseline characteristics stratified by tertiles of normal serum lactate dehydrogenase (LDH) levels
Characteristic Tertile p Value for Trend

1 2 3
(n ⫽ 1,860) (n ⫽ 1,888) (n ⫽ 1,771)

Serum lactate dehydrogenase (IU/L) —

Mean 135.4 ⫾ 10.7 159.6 ⫾ 6.0 190.4 ⫾ 16.9
Median 137 159 186
Range 100–149 150–170 171–260
Age (years) 46.2 ⫾ 7.3 47.0 ⫾ 7.3 47.7 ⫾ 7.7 ⬍0.001
Men 70.8% 75.5% 78.7% ⬍0.001
Blood pressure (mm Hg)
Systolic 118.0 ⫾ 14.0 121.0 ⫾ 14.9 123.6 ⫾ 15.6 ⬍0.001
Diastolic 75.5 ⫾ 9.1 77.5 ⫾ 9.6 79.1 ⫾ 9.9 ⬍0.001
Low-density lipoprotein cholesterol (mg/dl) 120.3 ⫾ 26.5 124.8 ⫾ 26.7 127.2 ⫾ 28.0 ⬍0.001
High-density lipoprotein cholesterol (mg/dl) 46.8 ⫾ 11.6 47.3 ⫾ 11.5 47.8 ⫾ 12.2 0.04
Triglycerides (mg/dl)
Median 104 108 111 ⬍0.001
Interquartile range 75–147 79–151 82–158
Body mass index (kg/m2) 25.1 ⫾ 3.5 25.8 ⫾ 3.4 26.7 ⫾ 3.9 ⬍0.001
Percentage of age-predicted maximal heart rate 0.06
⬍85% 3.0% 2.3% 2.8%
85%–100% 72.0% 69.8% 69.5%
ⱖ100% 21.4% 24.2% 25.3%
Leisure time activity (min/wk) 159.6 ⫾ 104.7 162.2 ⫾ 113.2 175.4 ⫾ 116.7 0.02
Cardiovascular family history* 22.2% 21.9% 22.8% 0.64
Current smoker 21.8% 17.7% 16.3% ⬍0.001

* Defined as reporting coronary artery disease in first-degree relative.

Table 2 Results
Leisure-time physical activity characteristics (N ⫽ 5,519)
The baseline characteristics of 5,519 adult men and
Characteristic % LDH (IU/L) p Value women (mean age 47.0 years, range 34 to 86), who were
Regular leisure time activity 0.001 followed up for a mean of 4.2 years (23,415 person-years),
Running 6.5% 165.9 ⫾ 26.3 are presented according to CAD outcome (Supplementary
Bicycling 3.1% 162.6 ⫾ 28.2 Table 1) and total serum LDH tertiles (Table 1).
Walking 30.2% 162.2 ⫾ 25.3 The overall incidence of CAD outcome in the cohort was
Gym workout 8.4% 161.1 ⫾ 26.7 6.1% (338 cases) during the follow-up period. In addition,
Swimming 3.6% 157.6 ⫾ 25.4 208 incident cases of diabetes mellitus (3.8%) and 14 inci-
Any other leisure time activity 8.2% 159.2 ⫾ 23.3 dent cases (0.3%) of cerebrovascular disease were recorded.
No regular leisure time activity 40.0% 160.6 ⫾ 24.9
At baseline, those who later developed CAD were signifi-
Weekly leisure time activity 0.04
(days/wk)
cantly older than those who did not have this outcome, were
1 5.0% 159.7 ⫾ 24.6 more often men, had greater systolic and diastolic blood
2 16.2% 160.4 ⫾ 25.9 pressures, greater low-density lipoprotein cholesterol and
3 13.6% 161.2 ⫾ 24.8 triglyceride levels, lower high-density lipoprotein cholesterol
4 5.2% 163.3 ⫾ 25.3 levels, poorer ergometry fitness levels, lower APMHR%, and
5 2.9% 164.9 ⫾ 27.8 also were less engaged in regular physical activity by 18.8%.
6 1.5% 163.8 ⫾ 28.4 The baseline mean LDH level was significantly lower in those
7 1.3% 168.2 ⫾ 27.9
who developed CAD during the follow-up period (Supplemen-
Intervals of leisure time activity 0.01
(min/wk)
tary Table 1).
ⱕ180 30.4% 160.6 ⫾ 25.2 Those in the greater LDH tertile also had significantly
181–240 4.2% 163.5 ⫾ 25.4 greater rates of these risk factors for CAD, apart from
241–360 4.8% 165.0 ⫾ 28.3 having a significantly lower rate of smokers, greater high-
⬎360 1.9% 166.1 ⫾ 28.7 density lipoprotein cholesterol, greater rate of APMHR%
Leisure-time activity duration 0.02 ⱖ100%, and greater mean weekly minutes of leisure time
(years) physical activity (Table 1).
⬍5 15.3% 159.9 ⫾ 25.4 All variables of leisure time physical activity collected in
ⱖ5 18.3% 162.7 ⫾ 26.0
our cohort population are listed in Table 2. Regular engage-
Data presented as percentages or mean ⫾ SD. ment in running, followed by bicycling and walking, was
significantly associated with greater mean total serum LDH
levels. Greater mean LDH levels were also significantly
1720 The American Journal of Cardiology (www.ajconline.org)

Table 3
Hazard ratios for coronary artery disease (CAD) according to tertiles of normal serum lactate dehydrogenase (LDH) levels
Variable Tertile p Value for Trend

1 2 3
(n ⫽ 1,860) (n ⫽ 1,888) (n ⫽ 1,771)

Serum lactate dehydrogenase levels (IU/L) 100–149 150–170 171–260 —

Person-years of follow-up 8,473 7,934 7,008 ⬍0.001
Incident cases of coronary artery disease (n) 140 (7.5%) 104 (5.5%) 94 (5.3%) 0.005
Adjusted hazard ratio (95% confidence interval)
Age and gender 1 0.74 (0.57–0.95) 0.70 (0.54–0.92) 0.01
Age, gender, percentage of age-predicted maximal heart rate, 1 0.75 (0.58–0.96) 0.72 (0.55–0.93) 0.02
and minutes/week of leisure time physical activity
Multivariate* 1 0.72 (0.56–0.94) 0.70 (0.54–0.92) 0.01

Data presented as range, n (%), or hazard ratio (95% confidence interval).

* Multivariate Cox proportional hazards model was adjusted for age, systolic blood pressure, body mass index, low-density lipoprotein cholesterol levels,
and triglyceride levels as continuous variables and gender (male or female), APMHR% (⬍85%, 85% to 99%, ⱖ100%, or missing), intervals of leisure time
physical activity (⬍150 or ⱖ150 min/wk, or none/missing), cardiovascular family history (positive or negative), and current smoker (yes or no).

Table 4
Lactate Physical activity characteristics of National Health and Nutrition
Dehydrogenase Examination Surveys (NHANES) participants aged ⱖ40 years with
0.99 Tertile
normal-range serum lactate dehydrogenase (LDH)
100 - 149 IU/L
150 - 170 IU/L Characteristic NHANES LDH (IU/L) p Value
Cumulative Survival Probability

171 - 260 IU/L

2007–2010
0.97 (n ⫽ 5,064)

Weekly vigorous-intensity 0.007

work activity (days/wk)
1–5 14.3% 133.3 ⫾ 21.7
0.95 6–7 3.7% 138.0 ⫾ 20.7
Intervals of vigorous-intensity 0.10
work (min/day)
⬍240 10.8% 133.2 ⫾ 21.4
0.93 ⱖ240 7.0% 135.7 ⫾ 21.6
Moderate-intensity work 0.03
activity
Yes 36.0% 135.9 ⫾ 21.8
0.91 No 64.0% 134.6 ⫾ 21.5
1 2 3 4 5 6 7 Intervals of moderate- 0.14
Follow-up Time (years) intensity work (min/day)
⬍300 29.6% 135.5 ⫾ 21.7
Figure 1. Multivariate-adjusted stratified survival curve for CAD according ⱖ300 6.3% 137.5 ⫾ 22.3
to tertiles of normal serum LDH levels among 5,519 men and women. Weekly transport-related 0.06
Multivariate Cox proportional hazards model adjusted for age, systolic activity (days/wk)
blood pressure, body mass index, low-density lipoprotein cholesterol, and 1–5 13.8% 133.0 ⫾ 22.6
triglycerides as continuous variables and gender (male or female), 6–7 10.0% 135.4 ⫾ 21.4
APMHR% (⬍85%, 85% to 99%, ⱖ100%, or missing), minutes of weekly Intervals of vigorous-intensity 0.09
leisure time physical activity (⬍150 or ⱖ150 min/wk or none/missing), recreational activities (min/
cardiovascular family history (positive or negative), and current smoker day)
(yes or no). p value ⫽ 0.01, for trend between normal serum LDH tertiles. ⬍120 11.7% 131.2 ⫾ 21.0
ⱖ120 2.9% 134.5 ⫾ 20.7
Sedentary activity (min/day) 0.01
associated with more days of the week practicing any reg- ⬍300 51.4% 135.8 ⫾ 21.5
ular leisure time activity, a greater number of total weekly ⱖ300 48.2% 134.2 ⫾ 21.6
minutes of activity, and practicing ⱖ5 years of regular
Data presented as percentages or mean ⫾ SD.
leisure time activity.
Adjusted for age and gender, the HRs for CAD dem-
onstrated a statistically significant descending HR gradi- the HRs (Table 3 and Figure 1). The HR for continuous
ent across the increased total serum LDH levels by ter- LDH (per 10-IU/L increment) in the same fully adjusted
tiles compared to the reference lower tertile (Table 3). multivariate model presented in Table 3 was 0.94 (95%
Additional adjustments for APMHR% and minutes per confidence interval 0.90 to 0.99, p ⫽ 0.01). No significant
week of leisure time physical activity, and the fully effect modification in regard to CAD morbidity outcome
adjusted multivariate model did not substantially change was found for the interaction between LDH and gender
 Coronary Artery Disease/LDH and CAD
within the same fully adjusted multivariate model pre-
sented in Table 3 (data not shown).
We also examined the association of total serum LDH
and various types of physical activity in all 5,064 NHANES
2007 to 2010 survey’ participants aged ⱖ40 years with
normal-range LDH who reported no heart disease, diabetes,
or stroke history. The mean LDH level was significantly
greater in those engaged in 6 or 7 days/wk of vigorous
intensity work activity versus 1 to 5 days/wk and in those
engaged in ⬍300 min/day of sedentary activity versus
ⱖ300 min/day. Other types and intensities of physical ac-
tivity also tended to be associated with greater mean LDH
levels in the greater duration or intensity category of activity
(Table 4 and Supplementary Table 2 for the fully disclosed
data).
Discussion
Our analysis of the low-cardiovascular-risk ambulatory
adult cohort demonstrated a significant association with
lower CAD occurrence among those with greater total se-
rum LDH levels within the normal laboratory range. More-
over, this association was significant, despite the signifi-
cantly greater rates of traditional CAD risk factors in the
middle and higher LDH tertiles at baseline (Table 1). We
also demonstrated, with statistical significance, that the
mean serum LDH level increased in parallel with the inten-
sity and duration of leisure time physical activity (dose–
response). Similarly, in the external cross-sectional valida-
tion analysis of the NHANES 2007–2010 surveys, we found
significant associations of greater mean LDH levels and an
increased duration and intensity of occupational physical
activity and a lower duration of sedentary daily activity
time.
A possible limitation of the present study could have been
the lack of sufficient retrospective data regarding alcohol con-
sumption. This factor might play a role as a confounder of an
observed association between LDH and CAD because it af-
fects both. However, regular alcohol consumption was signif-
icantly associated with lower normal-range LDH levels in our
NHANES 2005–2010 surveys’ analysis of 6,955 healthy am-
bulatory adult participants, with a significant dose–response
effect (Supplementary Table 2).
There are 5 major LDH isoenzymes; LDH-1 and LDH-2
are the major isoenzymes in cardiac muscle and erythro-
cytes and LDH-4 and LDH-5 in skeletal muscle and liver.
Usually, LDH-2 is the predominant form in the serum,
followed by LDH-1, -3, -4, and -5.1,15 Most serum LDH
comes from the breakdown of erythrocytes and platelets,
with additional isoenzymes from other organs in a compo-
sition that reflects their tissue origin. A significant increase
in serum levels occurs with little tissue breakdown or dam-
age.1 Total serum LDH elevation, consisting mainly of the
major skeletal muscle isoenzymes, LDH-4 and -5, was ob-
served immediately after strenuous, enduring, aerobic phys-
ical activity in athletes.5,6
Another major source of the elevated total serum LDH
level could be from the contribution of cardiac LDH isoen-
zymes. At myocardial ischemia, LDH increases gradually in
the serum. At this time, the LDH-1/LDH-2 ratio, which is
normally ⬍1, increases to ⬎1, which is known as the
1721
“flipped” ratio, and sometimes also appears after extreme
exercise.1,15–17 This phenomenon was also described in the
presence of transient myocardial ischemia signs at rest in 15
patients with CAD, all of whom had total serum LDH levels
within the top quintile of the normal laboratory range.18
Additional reports of 51 patients with CAD 48 hours after
ergometry19 and, notably, of 8 healthy off-season college
basketball players,20 have demonstrated a similar and sig-
nificant shift in cardiac LDH isoenzymes within the normal
range of total LDH and, specifically, within the top 2 nor-
mal-range quintiles for 7 of the players.
In our study, that the total serum LDH level retained its
independent association with CAD, despite adjusting for
physical activity and ergometry fitness levels, might imply
that other LDH isoenzymes, such as the major myocardium
LDH isoenzymes, LDH-1 and LDH-2, contribute to the
normal-range increase in total serum LDH, rather than the
skeletal muscle isoenzymes, LDH-4 and LDH-5.
Previous experimental studies of animal tissues or mod-
els, in particular, of the myocardium,21,22 striated muscle,23
kidney,24 and liver,25 have all demonstrated that under re-
versible, relatively short, hypoxic or ischemic conditions,
tissue-specific LDH isoenzymes are released from the cells
in moderate amounts until reoxygenation or reperfusion
occurs. If reoxygenation or reperfusion does not occur,
additional enzyme is continuously released and progression
to irreversible cell damage is induced.
These human and animal studies might strengthen the
notion that under certain transient and reversible anaerobic
stress conditions that can develop, for example, in response
to an increased intensity and duration of aerobic physical
activity, modest extracellular release of tissue-specific LDH
might correspond to greater total serum LDH levels, al-
though still within the normal limit. Furthermore, this phe-
nomenon could indirectly imply a better ability of body
tissues and organs to withstand pathologic ischemic stress.
Eventually, this might be reflected in a lower CAD morbid-
ity rate in such healthy, physically active, populations.
Supplementary Data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/
j.amjcard.2012.08.005.
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