Relation of Alanine Aminotransferase Levels to

Cardiovascular Events and Statin Efcacy

Paulo H.N. Harada, MD, MPH, PhDa, Nancy R. Cook, ScDa, David E. Cohen, MD, PhDb,
Nina P. Paynter, PhDa, Lynda Rose, MSa, and Paul M Ridker, MD, MPHa,*

The relation between hepatic serum markers within the normal range and cardiovascular
risk is uncertain. We sought to address this issue within a prospective randomized trial of
statin therapy. Men and women (n [ 17,515) free of cardiovascular disease participating in a
randomized placebo controlled trial of rosuvastatin 20 mg/day had baseline levels of alanine
aminotransferase (ALT) below <40 IU/l and were followed prospectively for the rst-ever
cardiovascular events. Cox proportional hazards models were used to calculate the relative
risks of these events according to increasing tertiles and each SD increase in baseline ALT
levels. ALT levels at study entry, all within the normal range, were inversely associated with
age, smoking status, and inammation and were positively associated with male gender,
alcohol use, and triglycerides. Incident cardiovascular event rates were highest in those in the
lowest tertile of baseline ALT; specically, incidence rates were 1.43, 0.98, and 0.85 per 100
person-years of exposure for those in the lowest, middle, and highest tertile of baseline ALT
within the normal range, respectively (p <0.001). These inverse effects remained statistically
signicant after multivariate adjustment for a wide range of vascular risk factors risk
markers such that each higher SD unit of ALT was associated with an 18% lower event rate
(relative risk 0.82, 95% condence interval 0.72 to 0.93, p [ 0.002). The efcacy of statin
therapy was not modied by baseline ALT level. In conclusion, increasing ALT levels within
the normal range are inversely associated with future cardiovascular risk but had limited
clinical utility and also did not modify the efcacy of statin therapy. 2016 Elsevier Inc.
All rights reserved. (Am J Cardiol 2016;118:49e55)

Alanine aminotransferase (ALT) is released by the liver
both in pathologic and normal physiological conditions.
Clinically, levels of ALT above the upper limit of normality
have been associated with increased risks for hepatic and
cardiovascular events,1 in part due to underlying nonalcoholic
fatty liver disease (NAFLD) and its consequent effects on
metabolic dysfunction and diabetes.2,3 Besides, statin therapy
can increase ALT levels and elevations over 3 times the upper
normal limit of ALT have in turn been considered a relative
contraindication for therapy with this class of lipid-lowering
agent.4 In contrast, recent data have suggested an apparent
paradox between ALT levels within the normal range, inci-
dent vascular event rates, and the efcacy of statin therapy. In
particular, prospective cohort studies have reported inverse
relations between ALT levels within the normal range and
subsequent risks for cardiovascular events and all-cause
mortality such that those in higher ALT stratum have
reduced event rates versus those in the lower ALT group.5e7
Furthermore, reports from 2 statin trials have suggested that
a
Center for Cardiovascular Disease Prevention, Divisions of Preventive
Medicine and Cardiovascular Diseases, and bDivision of Gastroenterology,
Brigham and Womens Hospital, Harvard Medical School, Boston, Mas-
sachusetts. Manuscript received December 9, 2015; revised manuscript
received and accepted April 8, 2016.
Funding Sources: The JUPITER trial was supported by an investigator-
initiated research grant from AstraZeneca.
Clinical Trial Registration: ClinicalTrial.gov NCT00239681.
See page 54 for disclosure information.
*Corresponding author: Tel: (617) 732-8790; fax: (617) 734-1508.
E-mail address: pridker@partners.org (P.M. Ridker).
those with ALT levels higher than the upper limit of normal
obtain a greater relative risk reduction from lipid-lowering
therapy versus those with normal ALT levels.8,9 Whether
the efcacy of statin therapy is modied by ALT levels within
the normal range, however, is uncertain. We addressed these
issues in the Justication for the Use of statins in Prevention:
an Intervention Trial Evaluating Rosuvastatin (JUPITER)
trial, a contemporary randomized double-blind placebo-
controlled evaluation of rosuvastatin 20 mg. That trial
included 17,515 apparently healthy men and women with
ALT levels
40 IU/l who were followed prospectively for
future vascular events.10
Methods
The sample was derived from JUPITER (ClinicalTrial.
gov NCT00239681), a randomized, double-blind, placebo-
controlled trial designed to investigate whether rosuvastatin
20 mg/day compared to placebo decreases the rate of the
rst-ever cardiovascular events in apparently healthy men
aged >50 years and women >60 years with low-density
lipoprotein (LDL) cholesterol <130 mg/dl who were at
increased vascular risk because of a high-sensitivity C
reactive protein (hsCRP) level 2 mg/l.10 The full details of
the trial protocol have been previously presented.10 The trial
exclusion criteria included diabetes, treatment with any
lipid-lowering therapy in the 6 weeks preceding randomi-
zation, current use of postmenopausal hormonal replace-
ment therapy, previously known ALT levels higher than 2
times the upper limit of normal, creatinine >2.0 mg/dl,
uncontrolled hypertension or hypothyroidism, a history of

0002-9149/16/$ - see front matter 2016 Elsevier Inc. All rights reserved. www.ajconline.org
http://dx.doi.org/10.1016/j.amjcard.2016.04.012
50 The American Journal of Cardiology (www.ajconline.org)

Table 1
Baseline clinical characteristics of the study population according to increasing tertiles of alanine aminotransferase measured at study entry
ALT Range (IU/L) Lower Intermediate Higher p value

11 12-16 >16

N 5505 N 5896 N 6114

Age (years) 68.8 (7.7) 66.4 (7.4) 63.6 (7.1) <0.001

Men 48.2% 60.5% 74.6% <0.001
Body mass index (kg/m2) 27.9 (6.0) 28.9 (5.4) 30.0 (5.7) <0.001
Waist Circumference (cm) 95.5 (13.6) 98.7 (14.1) 102.3 (13.2) <0.001
Alcohol 1 drink per day 13.3% 18.3% 23.4% <0.001
Current Smoker 18.6% 15.0% 14.1% <0.001
Estimated Glomerular Filtration Rate (ml/min) 74.3 (18.8) 74.9 (17.1) 76.6 (16.3) <0.001
Family History of Early Coronary Heart Disease 10.8% 11.6% 12.2% 0.068
Metabolic Syndrome 33.9% 39.5% 50.5% <0.001
Hypertension 57.2% 56.6% 57.9% 0.361
Systolic Blood Pressure (mmHg) 135 (17) 136 (17) 136 (17) <0.001
Diastolic Blood Pressure (mmHg) 80 (9) 81 (9) 82 (9) <0.001
Fasting Glucose (mg/dl) 92.7 (11.1) 94.7 (11.5) 96.8 (11.9) <0.001
HbA1C (%) 5.7 (0.5) 5.7 (0.4) 5.7 (0.4) 0.200
Total Cholesterol (mg/dl) 182 (25) 184 (24) 184 (24) <0.001
HDL Cholesterol (mg/dl) 53.3 (15.6) 51.7 (15.0) 49.2 (14.9) <0.001
LDL Cholesterol (mg/dl) 104 (19) 105 (18) 104 (19) 0.748
Triglycerides (mg/dl)* 107 (80 e 149) 117 (84 e 166) 132 (93 e 193) <0.001
Apolipoprotein-a (mg/dl) 167 (31) 166 (31) 164 (30) <0.001
Apolipoprotein-b (mg/dl) 105 (21) 109 (21) 112 (22) <0.001
High sensitive C Reactive Protein (mg/L)* 4.7 (3.0 - 8.3) 4.2 (2.8 - 6.8) 4.1 (2.8 - 6.5) <0.001
Framingham Risk Score* 10 (5 e 16) 10 (6 e 16) 11 (6 e 16) <0.001
Reynolds Risk Score* 10.0 (5.5 e 17.3) 9.6 (5.6 e 16.1) 9.4 (5.9 e 15.5) 0.009
Drug (Rosuvastatin) 50.0% 50.2% 49.6% 0.801
Delta LDL Cholesterol (mg/dL) -14 (-49 e 6) -12 (-51 e 7) -14 (-51 - 7) 0.521

Continuous variables expressed by means (standard deviations) or median (interquartile range) signaled by *; meanwhile categorical ones expressed by
percentage unless otherwise specied. Delta LDL cholesterol LDL cholesterol at 12 months  baseline LDL cholesterol.

malignancy within 5 years, or another serious medical
condition that might compromise patient safety or success-
ful completion of the study.
Of 17,783 participants enrolled in this trial, 268 had
baseline ALT levels >40 IU/l, the upper normal limit cutoff
in the trial. Thus, the present analysis included 17,515
participants with baseline ALT levels within the study
normal limits. Differences in clinical characteristics and 10-
year predicted risk Framingham-based ATP-III risk esti-
mator11 and Reynolds risk score12,13 between those in each
ALT tertile were tested for trend by linear regression if
normal and Jonckheere-Terpstra for nonparametric or cate-
gorical variables. We displayed the age- and gender-
adjusted cumulative incident cardiovascular events curves
for ALT tertiles and the age- and gender-adjusted hazard
ratios (HRs) of the second and third tertiles versus the rst.
The relation of baseline ALT levels with future vascular
events was addressed by its tertiles and SD units in Cox
proportional hazards models to calculate crude and adjusted
incidence rates for the composite end point of myocardial
infarction, stroke, arterial revascularization, hospitalization
for unstable angina pectoris, or death from cardiovascular
causes. Models were adjusted for age, gender, waist
circumference, smoking status, alcohol consumption, sys-
tolic blood pressure, fasting glucose, plasma lipid levels,
statin treatment, and hsCRP. Effect modication was
addressed by stratied analyses according to age categories
(<65 and 65 years), gender, smoking status, waist
circumference categories (normal
102 cm for men and

88 cm for women, and abnormal otherwise), alcohol
consumption categories (no or infrequent use if less than
weekly consumption and regular otherwise), metabolic
syndrome, and Reynolds risk score (<7.5% and 7.5%)
categories. Rosuvastatin relative risk reductions were
compared to placebo for each ALT tertile to evaluate effect
modication. We also displayed the age- and gender-
adjusted cumulative incident cardiovascular events curves
for treatment arms within each ALT tertile and the age- and
gender-adjusted HRs for rosuvastatin versus placebo. To
address the HR for events across the ALT range in a more
exible way, we plotted adjusted smoothed spline with ALT
knots at the 5, 25, 50, 75, and 95 percentiles values.
Cardiovascular risk prediction based on Reynolds risk
score was compared in models with and without the addition of
ALT in nonstatin users. The Reynolds risk score predicts
cardiovascular death, myocardial infarction, stroke, and cor-
onary revascularization. We compared C-statistics for the 2
models and computed the integrated discrimination improve-
ment (IDI) and relative IDI and categorical net reclassication
improvement (NRI). The group cutoffs for NRI were 1% and
1.5%, which correspond to 5% and 7.5% risk in 10 years of
follow-up assuming events accumulate linearly every 2 years.
JUPITER was an investigator-initiated trial. The sponsor
of the study collected the trial data and monitored the study
sites but had no access to unblinded data until after the
drafting of the trial primary report. All statistical analyses
 Preventive Cardiology/ALT Levels, Statins, and Vascular Events 51

Figure 1. Cardiovascular events accumulated incidence by ALT tertiles. Age- and gender-adjusted cumulative incidence of cardiovascular events in the
JUPITER trial according to increasing tertile of ALT levels within the normal range. ALT tertiles: L for lower, I for intermediate, and H for higher. HR: age-
and gender-adjusted hazard ratio for vascular events.

Table 2
Baseline levels of alanine aminotransferase and the risk of future cardiovascular events
ALT Range (IU/L) Lower Tertile Intermediate Tertile Higher Tertile p value for trend HR per 1-SD p value
Increase

11 (N5505) 12-16 (N5896) >16 (N6114)

Primary Events (%) 163 (3.0%) 122 (2.1%) 107 (1.8%)

Cardiovascular Death (%) 33 (0.6%) 15 (0.3%) 16 (0.3%)
Stroke (%) 54 (1.0%) 22 (0.4%) 19 (0.3%)
Myocardial Infarction (%) 33 (0.6%) 38 (0.6%) 25 (0.4%)
Hosp. Unstable Angina (%) 15 (0.3%) 10 (0.2%) 17 (0.3%)
Arterial Revascularization (%) 46 (0.8%) 55 (0.9%) 45 (0.7%)
Primary Events/100 person years 1.43 0.98 0.85
HR Primary Event (Model 1) Ref. 0.73 (0.58 - 0.93) 0.68 (0.53 - 0.88) 0.003 0.78 (0.69 - 0.89) <0.001
HR Primary Event (Model 2) Ref. 0.77 (0.60 - 0.98) 0.73 (0.56 - 0.96) 0.017 0.81 (0.72 - 0.92) 0.001
HR Primary Event (Model 3) Ref. 0.78 (0.61 - 0.99) 0.74 (0.57 - 0.97) 0.025 0.82 (0.72 - 0.93) 0.002

Cardiovascular death, stroke, myocardial infarction, hospitalization for unstable angina and arterial revascularization events outnumber primary events in
each tertile due to the occurrence of 2 simultaneous events as part of the primary outcome.
Cox proportional model: Hazards ratio (HR) (95% Condence Interval) for composite primary outcome.
Right-hand of the table hazards ratio of alanine aminotransferase per each standard deviation (SD) unit.
Model 1: Age and gender adjusted.
Model 2: Model 1 plus waist circumference, smoking status, alcohol consumption, blood pressure, fasting glucose, HDL cholesterol, log triglycerides and
treatment arm.
Model 3: Model 2 log C reactive protein.

were done by the investigators and the academic study
statistician. Trial principal investigator (P.M.R.) had full
access to all study data and had nal responsibility for the
decision to submit these data for publication.
Results
JUPITER trial participants in the lowest tertile of ALT
(
11 IU/l) were signicantly older than those in the highest
tertile (>16 IU/l), were more likely to smoke, had moder-
ately higher levels of hsCRP, and a higher Reynolds risk
score (Table 1). In contrast, those in the highest tertile of
ALT at baseline were more likely to be men, had more
prevalent daily alcohol consumption, higher body mass in-
dex, and higher levels of triglycerides. Despite younger age,
those in the highest baseline tertile of ALT had a signi-
cantly greater prevalence of metabolic syndrome, had more
52 The American Journal of Cardiology (www.ajconline.org)

Table 3
Stratied levels of ALT and the risk of future cardiovascular events
Events / N HR per 1-SD Increase p value P for
interaction

<65 years 117 / 7275 0.82 (0.66 - 1.02) 0.075 0.706

65 years 275 / 10240 0.83 (0.72 - 0.97) 0.015
Male 283 / 10782 0.84 (0.73 - 0.98) 0.023 0.087
Female 109 / 6733 0.73 (0.56 e 0.95) 0.018
Non smokers 298 / 14742 0.78 (0.67 - 0.91) 0.001 0.364
Smokers 94 / 2766 0.95 (0.75 - 1.21) 0.685
Placebo 250 / 8769 0.83 (0.71 - 0.97) 0.020 0.525
Rosuvastatin 142 / 8746 0.81 (0.65 - 1.00) 0.050
Normal WC 200 / 8479 0.82 (0.69 - 0.97) 0.022 0.808
Increased WC 192 / 9036 0.81 (0.67 - 0.97) 0.021
No or Infrequent 235 / 10268 0.86 (0.73 - 1.01) 0.058 0.781
Alcohol
Regular Alcohol 157 / 7240 0.78 (0.64 - 0.96) 0.019
Figure 2. ALT levels and adjusted hazard ratio for cardiovascular events. No Metabolic 222 / 10165 0.84 (0.71 - 0.99) 0.037 0.754
Adjustment for age, gender, waist circumference, smoking status, alcohol Syndrome
consumption, blood pressure, fasting glucose, high-density lipoprotein Metabolic 168 / 7228 0.79 (0.65 - 0.96) 0.016
cholesterol, log triglycerides, treatment arm, and log hsCRP. Spline y axis in Syndrome
log scale and knots at 5, 25, 50, 75, and 95 percentiles of ALT distribution. Reynolds <7.5 55 / 6570 0.66 (0.45 - 0.96) 0.028 0.215
Reynolds 7.5 335 / 10856 0.85 (0.74 - 0.97) 0.016
coronary heart disease risk factors, and higher Framingham
risk score. Finally, the LDL reduction after 1 year was Cox proportional model: Hazards ratio (HR) (95% Condence Interval).
Model adjustment: Age, gender, waist circumference, smoking status,
similar across the tertiles.
alcohol consumption, blood pressure, fasting glucose, HDL cholesterol, log
As shown in the age- and gender-adjusted data of triglycerides, treatment arm and log C reactive protein. WC (waist
Figure 1, those in the lowest tertile of baseline ALT had the circumference): normal WC, men
102 and women
88 cm; and
highest rates of future cardiovascular events during the 5- abnormal otherwise. No or infrequent alcohol, no or less than weekly
year follow-up period. Specically, Table 2 reports inci- consumption; and Regular Alcohol otherwise.
dence rates of 1.43, 0.98, and 0.85 per 100 person-years of
exposure for those in the lower, intermediate, and higher
tertile of baseline ALT within the normal range, respectively Table 4
Relative risk reduction of cardiovascular events by rosuvastatin as
(p <0.001). These effects persisted after adjustment for age,
compared to placebo, stratied by normal range ALT tertiles
smoking, gender, waist circumference, blood pressure,
glucose, high-density lipoprotein cholesterol, triglycerides, Incident Events/100 RR 95% CI p Value
alcohol use, statin treatment, and hsCRP such that each Person Years
increasing SD of ALT was associated with an 18% multi- Placebo Rosuvastatin
variate adjusted decrease in risk (95% condence interval
[CI] 0.72 to 0.93, p 0.002). The HR splines displayed in Lower Tertile 1.82 1.05 0.58 0.42 - 0.79 0.001
Figure 2 conrms the monotonic decreasing risk of vascular Intermediate Tertile 1.20 0.77 0.66 0.46 - 0.95 0.015
Higher Tertile 1.14 0.54 0.48 0.32 - 0.72 <0.001
events with increasing ALT values within the normal ALT
range. As reported in Table 1, this direction of effect was p for trend: comparison of incident cardiovascular rates among ALT
concordant with projected Reynolds but opposite to Fra- tertiles in each treatment branch.
mingham Risk Scores for this cohort. Effects were consis-
tent in all clinical strata evaluated (Table 3).
Overall in the JUPITER trial, rosuvastatin reduced the trial increasing ALT levels within the normal range are inversely
primary end point by 44% (HR 0.56; 95% CI 0.46 to 0.69; p related to the development of future cardiovascular events.
<0.001). As reported in Table 4 and Figure 3, similar effects This effect was equally observed in men and women.
were observed within each tertile of baseline ALT. However, in contrast to some previous studies limited to
When added to components of the Reynolds risk score, those with elevated ALT levels, we observed that the ef-
ALT did not signicantly change the area under the receiver cacy of statin therapy in preventing the rst major cardio-
operating characteristic curve (0.690; 95% CI 0.654 to 0.727 vascular events was similar in magnitude for those with
vs 0.700; 95% CI 0.665 to 0.734; p 0.701), had a minimal lower, intermediate, and higher levels of baseline ALT, all
impact on IDI (0.0015, 95% CI 0.0008 to 0.0026) and relative within the normal range.
IDI (11.9%, 95% CI 5.6% to 18.0%), and no signicant effect As previous work has shown increasing ALT levels in
on categorical NRI (0.014, 95% CI 0.037 to 0.063). the normal range are associated with insulin resistance,
metabolic syndrome, and NAFLD, it may seem paradoxical
that lower ALT levels predict greater cardiovascular risk.
Discussion
However, although the inverse relation between ALT levels
In this large-scale contemporary study of more than and vascular risk observed here is not widely appreciated,
17,000 initially healthy men and women, we found that our data are consistent with data from some previous
 Preventive Cardiology/ALT Levels, Statins, and Vascular Events 53

Figure 3. Cardiovascular events accumulated incidence by treatment arm within each ALT tertile. (A) Lower tertile, (B) intermediate tertile, and (C) higher
tertile. Unadjusted cumulative incidence of cardiovascular events in the JUPITER trial according to treatment arm stratied by ALT tertile.
54 The American Journal of Cardiology (www.ajconline.org)
cohorts.5e7 It is uncertain which components of vascular
risk are responsible for this inverse relation, particularly as
the effect of ALT on future vascular events remained sta-
tistically signicant after adjustment for traditional risk
factors. Also, our study is underpowered to address indi-
vidual components of the primary outcome. Furthermore, as
shown in our data of Table 1, the distribution of traditional
vascular risk factors did not directly parallel ALT levels; for
example, although those in the lowest tertile of ALT were
older and somewhat more likely to smoke, they were also
thinner, more likely to be women, and less likely to have
metabolic syndrome. Also interesting is the nontraditional
lipid prole distribution across ALT tertiles; although LDL
cholesterol levels were similar across groups, higher apo-B
levels were observed in those with higher ALT levels as a
signal of insulin-resistant dislypidemia. Indeed, those in the
lower ALT tertile had higher observed vascular event rates
despite having fewer traditional risk factors. In this respect,
the risks associated with increasing ALT levels were
concordant with those predicted by the Reynolds risk score,
which takes into account systemic inammation. Although a
positive family history was, if anything, more prevalent in
those with higher baseline ALT levels, hsCRP levels were
higher in those with lower levels of ALT, despite being
thinner and having a reduced prevalence of metabolic syn-
drome. Thus, lower ALT levels may have reected an
augmented proinammatory response, which predisposes to
increased vascular event rates.14
Although our data are concordant with 3 previous stud-
ies,5e7 they differ somewhat from 2 other studies in which
increasing ALT levels were associated with neutral15 or
increased cardiovascular risk.16 However, these 2 previous
studies did not exclude patients with above-normal ALT
levels in their sample selection. Moreover, closer examina-
tion of these 2 studies demonstrates, if anything, an inverse
relation of ALT levels in the normal range while the pos-
itive nding is driven largely by those participants with the
ALT levels well above normal.
Our ndings are limited to nondiabetic patients who
qualied for the JUPITER trial. However, Schooling et al.6
has reported a similar association between lower ALT levels
and greater risk of ischemic heart disease deaths not related
to diabetes but an opposite association in diabetes related
events. Our population comprised subjects aged >50 years
with hsCRP >2 mg/l at entry. In this regard, Kunutsor et al.7
addressed the effect modication of age and hsCRP on the
association of ALT with cardiovascular risk. In that study,
ALT was inversely associated with cardiovascular risk in
subjects aged >50 years and with elevated hsCRP but not
among younger patients with lower hsCRP.
Plasma ALT levels are measurements of enzyme released
from the cytosol of hepatocytes and generally reect rates of
cellular injury and turnover within the liver. Normal ALT
levels presumably reect low rates of ongoing hepatocyte
turnover, whereas increased levels are observed in the
setting of inammation, infection, toxic injury, and hypoxia.
ALT levels decrease with age,17e19 an effect attributed to
decreases in hepatocyte number that may reect age-related
increases in oxidative stress that promote apoptosis.19,20
Thus, one potential hypothesis deriving from our data is
that reduced hepatic mass and atherosclerotic disease share
common underlying pathophysiology. Currently, there is no
reliable method to evaluate hepatic mass, which limits
addressing this mechanism.
An alternative explanation of our data may be that ALT
is associated with increased mortality due to aging-
associated frailty.17Under normal circumstances, muscle
makes only a small contribution of plasma ALT activity.
However, in the setting of age-dependent reductions in
functional liver volume, the contribution of muscle to
plasma ALT could be proportionally increased. We note,
however, that adjusting our data for either exercise or
plasma creatinine kinase activities did not inuence the
relation between ALT and cardiovascular disease risk.
A potential limitation of our data is that the JUPITER
trial did not include diabetic patients. We also have no data
on NAFLD, which could be a link between ALT levels and
cardiovascular disease risk. Other point is potential bias
from ordinary uctuations in ALT. In this regard Miyake
et al21 demonstrated seasonal uctuations of ALT in
outpatient setting, with 6% increment in the winter. Ac-
counting for that, however, probably will not inuence the
linear association demonstrated in a signicant way. Finally,
despite the wide number of covariates available, we cannot
eliminate the possibility of residual confounding in these
data.
In this contemporary study of otherwise healthy men and
women, lower ALT levels within the normal range predict
greater cardiovascular risk, independent of traditional car-
diovascular risk markers. However, the measurement of
ALT did not improve the ability to reclassify vascular risk
over and above that already achievable with traditional risk
factors. We observed no evidence that the efcacy of statin
therapy in terms of reducing the rst-ever vascular events
was modied by underlying ALT levels.
Acknowledgment: The authors are grateful for the
outstanding support from Lemann Foundation, a nonprot
organization, and for the commitment and support of Latha
Padmanabhan, MS through the process of this project.
Disclosures
Dr. Ridker received an investigator-initiated grant from
AstraZeneca to conduct the JUPITER trial. Dr. Cohen has
received consulting fees from Aegerion, Dignity Sciences,
Genzyme, Intercept, Merck, Cymabay, and Novartis and has
additionally received honoraria from Merck. Dr. Harada
receives scholarship from Leman Foundation, a nonprot
organization. Lynda Rose, Dr. Paynter, and Nancy Cook
have nothing to disclose.
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