Scandinavian Cardiovascular Journal

ISSN: 1401-7431 (Print) 1651-2006 (Online) Journal homepage: https://www.tandfonline.com/loi/icdv20

Association between lipid fractions and age of first

myocardial infarction

Henrik Bødtker, Stine Gunnersen, Kasper Adelborg, Imra Kulenovic, Helle

Kanstrup, Erling Falk, Jens Meldgaard Bruun & Martin Bødtker Mortensen

To cite this article: Henrik Bødtker, Stine Gunnersen, Kasper Adelborg, Imra Kulenovic, Helle
Kanstrup, Erling Falk, Jens Meldgaard Bruun & Martin Bødtker Mortensen (2020): Association
between lipid fractions and age of first myocardial infarction, Scandinavian Cardiovascular Journal,
DOI: 10.1080/14017431.2020.1770850

To link to this article: https://doi.org/10.1080/14017431.2020.1770850

View supplementary material

Published online: 02 Jun 2020.

Submit your article to this journal

Article views: 15

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=icdv20
SCANDINAVIAN CARDIOVASCULAR JOURNAL
https://doi.org/10.1080/14017431.2020.1770850

ORIGINAL ARTICLE

Association between lipid fractions and age of first myocardial infarction

Henrik Bødtkera,b, Stine Gunnersena,c, Kasper Adelborgd, Imra Kulenovica, Helle Kanstrupc, Erling Falka,c,
Jens Meldgaard Bruuna,e and Martin Bødtker Mortensena,c
a
Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark; bDepartment of Emergency Medicine, Regional Hospital Herning,
Herning, Denmark; cDepartment of Cardiology, Aarhus University Hospital, Aarhus, Denmark; dDepartment of Clinical Epidemiology, Aarhus
University Hospital, Aarhus, Denmark; eSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

ABSTRACT ARTICLE HISTORY

Objective. Dyslipidemia is a major cause of early coronary heart disease (CHD). Low-density-lipoprotein Received 21 October 2019
cholesterol (LDL-C), remnant cholesterol (remnant-C) and high-density lipoprotein cholesterol (HDL-C) Revised 28 March 2020
have all been shown to be associated with risk of CHD. We aimed to compare the association of these Accepted 17 April 2020
lipid fractions with age at first myocardial infarction(MI). Design. Multicenter study of consecutive
KEYWORDS
patients hospitalized with a first MI. Linear regression models were used to assess the independent Myocardial infarction;
association of LDL-C, remnant-C and HDL-C with age at first MI. Results. The study included 1744 cholesterol; lipids; LDL-
patients. In univariate analyses, LDL-C, remnant-C, and HDL-C were all significantly associated with age cholesterol; remnant
at first MI. However, in multivariate analyses only LDL-C [
2.5 years (95%CI:
3.1 to
1.8) per 1 SD cholesterol
increase] and to a lesser extent remnant-C [
0.9 years (95% CI:
1.5 to
0.3)] continued to be associ-
ated with age of MI, while HDL-C [0.5 years (95%CI:
0.2 to 1.2)] was not. Conclusions. LDL-C is the
lipid fraction strongest associated with younger age of presentation of first MI. These results support
the importance of controlling and treating LDL-C in prevention of premature MI.

Introduction at first MI in a large cohort of consecutive patients hospital-

Dyslipidemia is a strong and modifiable risk factor for
development of atherosclerosis and coronary heart disease
(CHD), including myocardial infarction (MI) [1]. As CHD
remains a leading cause of morbidity and mortality world-
wide, detection and treatment of risk factors for CHD are
essential to prevent undue loss of life, increase quality of life
and reduce treatment costs [2,3].
Total cholesterol is a measure of the overall amount of
cholesterol in the circulation. Because cholesterol is not sol-
uble in water, it is transported in distinct lipoproteins.
Based on the density and protein content of these lipopro-
teins, total cholesterol can be subdivided into low-density
lipoprotein cholesterol (LDL-C), remnant cholesterol (rem-
nant-C) and high-density lipoprotein cholesterol (HDL-C).
Remnant-C is a combined measure of cholesterol content in
triglyceride-rich lipoproteins and consists of very low-dens-
ity lipoproteins (VLDL), intermediate-density lipoproteins
(IDL), chylomicrons and chylomicron remnants. Multiple
observations from both observational and clinical studies
have shown that elevated LDL-C and remnant-C are inde-
pendently associated with increased risk of CHD while ele-
vated HDL-C is independently associated with decreased
risk of CHD [4–10]. However, little data exist on the associ-
ation between these lipid fractions and the age of developing
a first CHD event. Thus, in the present study, we compared
the association of LDL-C, remnant-C and HDL-C with age
ized with a first MI between 2010 and 2012. Further, to
explore potential pathogenic mechanisms, we examined the
association of the lipid-fractions with coronary atheroscler-
osis as assessed by coronary artery calcification (CAC) in
patients undergoing diagnostic coronary computed tomog-
raphy angiography (CCTA).
Materials and methods
Myocardial infarction cohort
For the purpose of the present study, we used a previously
reported study population [11–13]. The study population
consists of consecutive patients with a first MI without prior
atherosclerotic cardiovascular disease (ASCVD) hereafter
just called first MI admitted to the following four hospitals
in Denmark in 2010 to 2012: Aarhus University Hospital
and the Regional Hospitals in Randers, Herning, and
Horsens. The universal definition of MI is implemented in
Denmark, and patients were identified using the
International Classification of Disease 10th Revision (ICD-
10) codes I21.0 through I21.9. Total cholesterol, triglycerides
and HDL-C were measured in non-fasting state using stand-
ard hospital assays [10,14,15]. LDL cholesterol was calcu-
lated using the Friedewalds formula if triglycerides were
<4.0 mmol/L. Otherwise it was measured directly. Only
plasma cholesterol measured within 24 h of admission to the

CONTACT Martin Bødtker Mortensen Martin.bodtker.mortensen@ki.au.dk Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
Supplemental data for this article can be accessed here.
ß 2020 Informa UK Limited, trading as Taylor & Francis Group
2 H. BØDTKER ET AL.
hospital and/or from a prior contact to the health care sys-
tem was used in this study. Non-fasting remnant cholesterol
was calculated as non-fasting total cholesterol minus LDL-C
minus HDL-C, as previously described [10,14,15]. Smoking
status was self-reported. The blood pressure was obtained
prior to admission (if hospitalized previous year) or after
recovery from MI (before hospital discharge or at the first
visit to the rehabilitation clinic). Hypertension was defined
as use of blood pressure lowering medication prior to
admission or a systolic blood pressure >140 mmHg.
Cardiac computed tomography cohort
The cardiac computed tomography cohort included con-
secutive patients referred to Aarhus University Hospital for
a diagnostic CCTA. The Agatston CAC score was deter-
mined from electrocardiographically gated images using a
Philips 64-slice scanner. Patients with prior CHD, incom-
plete risk factor information and statin use were excluded.
Plasma cholesterol and blood pressure were measured prior
to the CCTA. Results from this cohort have never been pub-
lished before and have been analyzed exclusively for the pre-
sent study.
The study was approved by the Danish Data Protection
Agency (Reference: 2007-58-0010, int. ref: 1-16-02-46-12).
Registry studies do not require ethical approval in Denmark.
Statistical analysis
Baseline characteristics are presented as mean [±standard
deviation (SD)] and were compared with one-way ANOVA,
Mann–Whitney test or Chi-square test.
The association of risk factors (including lipid parame-
ters) with age at first MI was assessed using multivariable
linear regression analysis (age as the dependent variable).
The variables included in the model were gender, smoking,
diabetes, statin use, triglycerides and cholesterol fractions at
baseline. The output of these analyses (b-coefficients) repre-
sents the change in age at first MI by presence versus
absence of the covariate condition. The linear regression
models were validated with QQ-plots of residuals and by
plotting fitted vs. predicted values.
Table 1. Study population: contemporary and consecutive patients with first myocardial infarction.
All
Baseline characteristics n ¼ 1744
Gender, % – 63
Age, year 69.1 (3.0)
Current smoker, % 36
Total cholesterol, mmol/L 5.0 (1.2)
LDL-cholesterol, mmol/L 3.0 (1.1)
HDL-cholesterol, mmol/L 1.3 (0.4)
Triglycerides, mmol/L 1.5 (1.0)
Systolic blood pressure, mmHg 138 (21)
Hypertension, % 70
Diabetes, % 16
Antihypertensive medication, % 48
Statin, % 25
Data are presented as mean (standard deviation) or percentages.
LDL: low-density lipoprotein; HDL: high-density lipoprotein.
Logistic regression analyses were used to assess the asso-
ciation of LDL-C, remnant-C and HDL-C with development
of premature MI (age <60 in women and <55 in men) and
non-trivial coronary artery disease (here defined as CAC
score >100). These results are presented as odds ratio (OR)
with 95% confidence intervals (CI).
Analyses were performed using Stata/SE version 13.1
(StataCorp LP, College Station, TX).
Results
We identified 1965 consecutive patients with a first MI.
After excluding patients with missing information on base-
line characteristics, including the lipid profile, 1744 patients
were available for this study (Table 1). Mean age was
69.1 years and 37% were women.
Association of LDL-C, remnant-C and HDL-C with age at
first MI
First, we assessed the association of cardiovascular risk fac-
tors with age at first MI (Supplementary Figure 1). Smoking
and male gender were strongly associated with MI occurring
6.8 (95% CI: 4.5–7.1) and 5.8 (95% CI: 5.6–8.1) years earlier,
while diabetes and statin use were not. Per 1 mmol/L
increase in total cholesterol (LDL-C, remnant-C and HDL-C
combined) and triglycerides, MI occurred 1.6 (95% CI:
1.0–2.1) and 1.3 (95% CI: 0.6–1.9) years earlier, respectively.
We then assessed the association of LDL-C, remnant-C
and HDL-C, separately, with age at first MI. In univariate
analyses, all three lipid fractions were strongly associated
with age at first MI (Figure 1, upper left panel). Per
1 mmol/L increase in LDL-C, remnant-C and HDL-C, MI
occurred 2.5 years earlier, 3.0 years earlier and 4.0 years later,
respectively (p < .0001 for all). When adjusted for baseline
characteristics in multivariable analyses (Figure 1, upper
right panel), LDL-C (
2.2 years per 1 mmol/L increase (95%
CI:
2.8 to
1.6)) and remnant-C (
1.8 years per 1 mmol/L
increase (95% CI:
3.1 to
0.6) continued to be strongly
associated with age at first MI while HDL-C was not
(1.2 years, 95% CI:
0.4 to 2.7).
Reanalyzing the associations per 1 SD increase in LDL-C,
remnant-C and HDL-C, revealed that LDL-C is the lipid
Men Women
n ¼ 1101 n ¼ 643
37
66.8 (13.1) 72.9 (13.9)
39 30
4.9 (1.2) 5.1 (1.3)
3.0 (1.1) 3.1 (1.2)
1.2 (0.4) 1.5 (0.5)
1.6 (1.0) 1.5 (0.9)
138 (20) 139 (22)
66 75
15 18
43 57
24 26
 SCANDINAVIAN CARDIOVASCULAR JOURNAL 3

Figure 1. Association of low-density lipoprotein cholesterol (LDL-C), remnant cholesterol (remnant-C) and high-density lipoprotein cholesterol (HDL-C) with age at
first myocardial infarction. Upper panels: Per 1 mmol/L increase. Lower panels: Per 1 standard deviation (SD) increase. Left panels: Unadjusted estimates. Right pan-
els: Multivariable adjusted estimates. Adjusted for: gender, smoking, diabetes, LDL-C, HDL-C, remnant-C and statin use.

Figure 2. Association of extreme values of low-density lipoprotein cholesterol (LDL-C), remnant cholesterol (remnant-C) and high-density lipoprotein cholesterol
(HDL-C) with age at first myocardial infarction. Left panels: Unadjusted estimates. Right panels: Multivariable adjusted estimates. Adjusted for: gender, smoking,
diabetes, LDL-C, HDL-C, remnant-C and statin use.

fraction independently explaining most of the variation in
age at first MI (Figure 1, lower panels). Though not impres-
sive, LDL-C explained 2.7% (R2 ¼ 0.027) of the variation of
age at first MI compared to 0.4% for remnant-C (R2 ¼
0.004) and 0.1% for HDL-C (R2 ¼ 0.001). Consistent with
these findings, extreme values of LDL-C (5 vs <3 mmol/L)
were associated with age of first MI occurring 7.7 (95% CI:
4.6–10.8) years earlier in multivariable analyses (Figure 2).
Likewise, extreme values of remnant-C (1.5 vs <0.5 mmol/
L) were associated with MI occurring 5.7 (95% CI: 2.5–8.9)
years earlier. In contrast, extreme levels of HDL-C were not
significantly associated with MI occurring later.
4 H. BØDTKER ET AL.
Table 2. Association between lipid fractions and premature (<55 years in men and <60 years in women) myocardial infarction among patients with a first myo-
cardial infarction.
Unadjusted
Odds ratio (95% CI)
Characteristics for premature MI
Gender 2.01 (1.58–2.55)
Current smoking 2.69 (2.15–3.35)
Diabetes 0.55 (0.39–0.76)
Statin use 0.47 (0.35–0.62)
LDL-C, per SD change 1.51 (1.35–1.69)
Remnant-C per SD change 1.23 (1.10–1.37)
HDL-C, per SD change 0.75 (0.67–0.85)
Multivariable adjusted odds ratios with 95% confidence intervals (CI) calculated using logistic regression. Adjusted for: gender, smoking, diabetes, LDL-choles-
terol, HDL-cholesterol, remnant cholesterol and statin use.
LDL: low-density lipoprotein; HDL: high-density lipoprotein.
Association of LDL-C, remnant-C and HDL-C with
premature MI
In logistic regression modeling, the odds ratio for having
premature MI was 1.4 (95% CI: 1.2–1.6) per 1 SD increase
in LDL-C, 1.1 (95% CI 1.0–1.3) per 1 SD increase in rem-
nant-C and 0.9 (95% CI: 0.8–1.0) per 1 SD increase in
HDL-C (Table 2).
Association of LDL-C, remnant-C and HDL-C with
coronary artery atherosclerosis
To explore if these results could be mediated by LDL-C
being stronger associated with atherosclerosis than remnant-
C and HDL-C, we assessed the association of these lipid
fractions with coronary artery atherosclerosis as assessed by
an Agatston CAC score >100. Baseline characteristics of the
652 individuals available from the CCTA cohort are shown
in Supplementary Table 1. Both in the overall cohort as well
as among patients younger than 60 years of age, only LDL-C
was significantly associated with CAC > 100 with odds
ratios of 1.3 (95% CI 1.2–1.7) and 1.5 (95% CI 1.1–2.0),
respectively (Supplementary Table 2).
Discussion
In this study of 1744 consecutive patients hospitalized for a
first-time MI, we assessed the association of standard lipid
fractions with the age at first MI. For each SD increase in
LDL-C, age at first MI occurred 2.5 years earlier compared
to 0.9 years earlier for remnant-C and 0.5 years later for
HDL-C. These results indicate that LDL-C is the lipid frac-
tion explaining most of the variation in age at first MI. Our
study of patients undergoing diagnostic CCTA suggests this
may be explained by LDL-C being the lipid fraction stron-
gest associated with coronary atherosclerosis.
Lipid fractions and age at first MI
Both LDL-C and remnant-C have been shown to be causally
associated with development of MI [10]. The mechanism is
likely similar, that is, entrapment of the lipoproteins (LDL
and remnant particles) in the intima of the arterial wall.
However, some pathophysiological differences may exist.
Unlike LDL particles, remnant particles can be taken up by
Multivariable adjusted
Odds ratio (95% CI)
p Value for premature MI p Value
<.001 1.74 (1.34–2.27) <.001
<.001 2.42 (1.92–3.05) <.001
<.001 0.73 (0.51–1.04) .084
<.001 0.71 (0.51–0.97) .34
<.001 1.41 (1.24–1.59) <.001
<.001 1.13 (1.01–1.27) .043
<.001 0.87 (0.76–1.0) .048
macrophages in its native form (i.e. no need for modifica-
tion such as oxidation) and have been suggested to be the
major cause of vascular inflammation [16]. Despite these
potential pathophysiological differences, we found similar
differences in the age at first MI per 1 mmol/L increase in
LDL-C and remnant-C. However, per 1 SD increase, LDL-C
was associated with MI occurring much earlier than for
remnant-C. A plausible explanation why LDL-C observa-
tionally explains most of the variation of age at first MI is
that the concentration of LDL-C in plasma by far exceeds
the concentration of remnant-C. For example, in our MI
cohort 60% of total cholesterol was in LDL-C compared
to 14% for remnant-C. Accordingly, the population vari-
ation in LDL-C (interquartile range: 2.3–3.7 mmol/L) in
absolute values was much higher than for remnant-C (inter-
quartile range: 0.4–0.8 mmol/L).
Comparison with previous studies
To the best of our knowledge, our study is the first to spe-
cifically evaluate the impact of the different lipoprotein frac-
tions on age at a first MI. However, a few other studies
have investigated the association of dyslipidemia with age at
a first CHD event. Labos et al. [17] assessed the association
of traditional risk factors and a genetic risk score with age
at a first acute coronary syndrome among 460 patients. Like
in our study they found that smoking and male gender were
strongly associated with age at first acute coronary syn-
drome but, surprisingly, found that hypercholesterolemia
(defined as a history of hypercholesterolemia or usage of
lipid-lowering therapy) was not. In a much larger study of
111,847 patients from the CRUSADE registry (Can Rapid
Risk Stratification of Unstable Angina Patients Suppress
Adverse Outcomes With Early Implementation of the ACC/
AHA Guidelines), however, Madala et al. [18] found that
hyperlipidemia (defined as total cholesterol  5.2 mmol/L or
treatment with lipid-lowering medication) was slightly, but
significantly, associated with earlier age at first non-ST seg-
ment elevation MI.
Non-hypercholesterolemic cholesterol levels contributes
to age of MI
It is worth noting that using the dichotomous definitions of
hypercholesterolemia as done in the previous studies may

substantially underestimate the contribution of cholesterol
to age at first CHD event. First, many individuals with a
first MI have cholesterol levels within the “normal” range
and will not be classified as hypercholesterolemic [19–21].
In the INTERHEART study (Effect of potentially modifiable
risk factors associated with myocardial infarction in 52
countries) of 8998 patients with a first MI, for example,
average LDL-C was only 3.2 mmol/L [22]. Still, the
INTERHEART study showed that dyslipidemia was one of
the most important causes of premature MI with a popula-
tion attributable risk of 59% [1]. Consistent with the
results from our study, LDL-C values in the INTERHEART
study was higher in younger than older individuals with a
first MI [22]. Second, strong clinical trial evidence has
shown that individuals with “average” cholesterol levels gain
considerably risk reduction with lipid-lowering statin ther-
apy [23,24]. In JUPITER (Justification for the Use of Statins
in Prevention: An Intervention Trial Evaluating
Rosuvastatin), for example, rosuvastatin was shown to pro-
vide both a substantial CHD and mortality benefit among
individuals with a median total cholesterol and LDL-C level
of 4.8 mmol/L (186 mg/dL) and 2.8 mmol/L (108 mg/dL),
respectively. Based on such evidence, the 2013 American
College of Cardiology/American Heart Association (ACC/
AHA) guideline for treatment of blood cholesterol with sta-
tins, lowered the actionable LDL-C threshold down to
1.8 mmol/L (70 mg/dL) in combination with a 10-year risk
for atherosclerotic cardiovascular disease 7.5% [25]. The
same treatment threshold was kept unchanged in the
updated 2018 ACC/AHA guideline [26].
Why is cholesterol associated with age at MI?
Previous studies have clearly shown that cholesterol frac-
tions, in particularly LDL cholesterol, are associated with
development of MI. Our study demonstrates that even
among patients who all suffer from MI, cholesterol fractions
are not only associated with development of MI but also
associated with MI occurring substantially earlier. A poten-
tial explanation to this finding may be that cholesterol frac-
tions are more strongly related to early development of
atherosclerosis that occur in younger individuals. In support
of this, a previous study indicated that total cholesterol was
more associated with development of MI in younger than
elderly individuals [27]. Taken together, our data support
the strong focus on management of LDL cholesterol for pre-
venting premature MI [28].
Limitations and strengths
Our study has important strengths. The analysis was per-
formed in a large cohort of first-time MI patients with an
age, sex and risk factor distribution routinely seen in clinical
practice. This is important when assessing the real-life con-
tribution of each lipid fraction with age at first-time MI.
Limitations include the retrospective nature of our study
with assessment of some risk factors at the MI event.
Importantly, however, if plasma cholesterol was not
SCANDINAVIAN CARDIOVASCULAR JOURNAL 5
available from a prior contact with the health care system,
only plasma cholesterol values measured within 24 h of
admission to the hospital were used in our study. They have
been shown to represent true baseline (pre-event) choles-
terol values.
Conclusions
In conclusion, using a cohort of patients presenting with a
first-time MI, LDL-C was the lipid fraction most strongly
associated with age of MI followed by remnant-C. When
adjusted for baseline characteristics, such an association was
not found for HDL-C. These results support the importance
of controlling and treating LDL-C in prevention of early
presentation of MI.
Acknowledgements
The authors thank Jette Bertelsen, Ole May and Karen Kaae Dodt for
their assistance in collecting information on patients with first myocar-
dial infarction and Ole Gøtzsche for helping collecting data on patients
referred to computed tomography. The study was funded by Institute
of Clinical Medicine, Aarhus University, Denmark.
Disclosure statement
The authors report no conflict of interests.
Author statement
Henrik Bødtker and Martin Bødtker Mortensen takes responsibility for
all aspects of the reliability and freedom from bias of the data pre-
sented and their discussed interpretation.
Funding
This work was supported by Department of Clinical Institute, Aarhus
University Hospital, Denmark.
References
[1] Yusuf S, Hawken S, Ounpuu S, et al.; INTERHEART Study
Investigators. Effect of potentially modifiable risk factors associ-
ated with myocardial infarction in 52 countries (the
INTERHEART study): case-control study. Lancet. 2004;364:
937–952.
[2] Murray CJL, Lopez AD. Measuring the global burden of dis-
ease. N Engl J Med. 2013;369:448–457.
[3] Roth GA, Forouzanfar MH, Moran AE, et al. Demographic and
epidemiologic drivers of global cardiovascular mortality. N Engl
J Med. 2015;372:1333–1341.
[4] Kannel WB, Dawber TR, Kagan A, et al. Factors of risk in the
development of coronary heart disease-six year follow-up
experience. The Framingham Study. Ann Intern Med. 1961;55:
33–50.
[5] Castelli WP, Garrison RJ, Wilson PW, et al. Incidence of cor-
onary heart disease and lipoprotein cholesterol levels. The
Framingham Study. Jama. 1986;256:2835–2838.
[6] Gordon DJ, Probstfield JL, Garrison RJ, et al. High-density
lipoprotein cholesterol and cardiovascular disease. Four pro-
spective American studies. Circulation. 1989;79:8–15.
[7] Lewington S, Whitlock G, Clarke R, et al.; Prospective Studies
Collaboration. Blood cholesterol and vascular mortality by age,
6 H. BØDTKER ET AL.
sex, and blood pressure: a meta-analysis of individual data
from 61 prospective studies with 55,000 vascular deaths.
Lancet. 2007;370:1829–1839.
[8] Cholesterol Treatment Trialists’ (CTT) Collaboration; Baigent
C, Blackwell L, Emberson J, et al. Efficacy and safety of more
intensive lowering of LDL cholesterol: a meta-analysis of data
from 170,000 participants in 26 randomised trials. Lancet. 2010;
376:1670–1681.
[9] Cholesterol Treatment Trialists’ Ctt Collaborators; Mihaylova B,
Emberson J, Blackwell L, et al. The effects of lowering LDL
cholesterol with statin therapy in people at low risk of vascular
disease: meta-analysis of individual data from 27 randomised
trials. Lancet. 2012;380:581–590.
[10] Varbo A, Benn M, Tybjaerg-Hansen A, et al. Remnant choles-
terol as a causal risk factor for ischemic heart disease. J Am
Coll Cardiol. 2013;61:427–436.
[11] Kulenovic I, Mortensen MB, Bertelsen J, et al. Statin use prior
to first myocardial infarction in contemporary patients: ineffi-
cient and not gender equitable. Prev Med. 2016;83:63–69.
[12] Mortensen MB, Kulenovic I, Klausen IC, et al. Familial hyper-
cholesterolemia among unselected contemporary patients pre-
senting with first myocardial infarction: Prevalence, risk factor
burden, and impact on age at presentation. J Clin Lipidol.
2016;10:1145–1152.e1.
[13] Mortensen MB, Kulenovic I, Falk E. Statin use and cardiovas-
cular risk factors in diabetic patients developing a first myocar-
dial infarction. Cardiovasc Diabetol. 2016;15:81.
[14] Nordestgaard BG, Benn M, Schnohr P, et al. Nonfasting trigly-
cerides and risk of myocardial infarction, ischemic heart dis-
ease, and death in men and women. JAMA. 2007;298:299–308.
[15] Varbo A, Freiberg JJ, Nordestgaard BG. Extreme nonfasting
remnant cholesterol vs extreme LDL cholesterol as contributors
to cardiovascular disease and all-cause mortality in 90,000 indi-
viduals from the general population. Clin Chem. 2015;61:
533–543.
[16] Varbo A, Benn M, Tybjaerg-Hansen A, et al. Elevated remnant
cholesterol causes both low-grade inflammation and ischemic
heart disease, whereas elevated low-density lipoprotein choles-
terol causes ischemic heart disease without inflammation.
Circulation. 2013;128:1298–1309.
[17] Labos C, Wang RHL, Pilote L, et al. Traditional risk factors
and a Genetic Risk Score are associated with age of first acute
coronary syndrome. Heart. 2014;100:1620–1624.
[18] Madala MC, Franklin BA, Chen AY, et al.; CRUSADE
Investigators. Obesity and age of first non-ST-segment elevation
myocardial infarction. J Am Coll Cardiol . 2008;52:979–985.
[19] Akosah KO, Schaper A, Cogbill C, et al. Preventing myocardial
infarction in the young adult in the first place: how do the
National Cholesterol Education Panel III guidelines perform? J
Am Coll Cardiol . 2003;41:1475–1479.
[20] Sachdeva A, Cannon CP, Deedwania PC, et al. Lipid levels in
patients hospitalized with coronary artery disease: an analysis
of 136,905 hospitalizations in Get With The Guidelines. Am
Heart J. 2009;157:111–117.e112.
[21] Mortensen MB, Sivesgaard K, Jensen HK, et al. Traditional
SCORE-based health check fails to identify individuals who
develop acute myocardial infarction. Dan Med J. 2013;60:
A4629.
[22] Sniderman AD, Islam S, McQueen M, et al. Age and cardiovas-
cular risk attributable to apolipoprotein B, low-density lipopro-
tein cholesterol or non-high-density lipoprotein cholesterol. J
Am Heart Assoc. 2016;5:e003665.
[23] Ridker PM, Danielson E, Fonseca FAH, et al.; JUPITER Study
Group. Rosuvastatin to prevent vascular events in men and
women with elevated C-reactive protein. N Engl J Med. 2008;
359:2195–2207.
[24] Yusuf S, Bosch J, Dagenais G, et al. Cholesterol lowering in
intermediate-risk persons without cardiovascular disease. N
Engl J Med. 2016;374:2021–2031.
[25] Stone NJ, Robinson JG, Lichtenstein AH, et al.; American
College of Cardiology/American Heart Association Task Force
on Practice Guidelines. 2013 ACC/AHA guideline on the treat-
ment of blood cholesterol to reduce atherosclerotic cardiovascu-
lar risk in adults: a report of the American College of
Cardiology/American Heart Association Task Force on Practice
Guidelines. J Am Coll Cardiol. 2014;63:2889–2934.
[26] Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/
AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/
PCNA Guideline on the Management of Blood Cholesterol: A
Report of the American College of Cardiology/American Heart
Association Task Force on Clinical Practice Guidelines. J Am
Coll Cardiol. 2019;73:e285–e350.
[27] Gr€ansbo K, Almgren P, Nilsson PM, et al. Risk factor exposure
in individuals free from cardiovascular disease differs according
to age at first myocardial infarction. Eur Heart J. 2016;37:
1977–1981.
[28] Pitt B, Loscalzo J, Ycas J, et al. Lipid levels after acute coronary
syndromes. J Am Coll Cardiol. 2008;51:1440–1445.