Annals of Medicine and Surgery 75 (2022) 103368

Contents lists available at ScienceDirect

Annals of Medicine and Surgery

journal homepage: www.elsevier.com/locate/amsu

Cross-sectional Study

Profile of cardiovascular disease risk in type 2 diabetes mellitus patients

receiving statin therapy: A cross-sectional study
Yasmin Karimah Ikhsan a, Soebagijo Adi Soelistijo b, *, Johanes Nugroho Eko Putranto c
a
Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
b
Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga – Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
c
Department of Vascular and Cardiology Medicine, Faculty of Medicine, Universitas Airlangga – Dr. Soetomo General Academic Hospital, Surabaya, Indonesia

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Cardiovascular disease is still the number 1 cause of death globally. Meanwhile, type 2 diabetes
Atherosclerosis vascular disease mellitus (T2DM) is a risk factor for atherosclerosis vascular disease (ASCVD), so an assessment using Framing­
Framingham risk score ham Risk Score (FRS) is needed to predict the risk of ASCVD in the future.
Type 2 diabetes mellitus
Objective: Analyzing the risk factor of ASCVD using the Framingham Risk Score (FRS) in T2DM patients.
Methods: This study was conducted from July 2020 to July 2021, which the participants were measured for FRS
including age, gender, current smoking, diabetes, blood pressure (systolic), high-density lipoprotein (HDL)
cholesterol, total cholesterol (TC), and ASCVD risk score. The analysis employed multiple linear tests and ANOVA
tests with p < 0.05.
Results: Several ASCVD risk factors in T2DM patients were found, including gender (t = 6.015; p < 0.001), age (t
= 6.901; p < 0.001), HDL level (t = 2.287; p = 0.024), CT level (t = 5.273; p < 0.001), blood pressure (t = 5.850;
p < 0.001), and current smoking (t = 2.638; p = 0.009). The results of analysis between ASCVD risk factor and
level of ASCVD risk obtained a significant association (F = 36,642; p < 0.001).
Conclusion: Risk factors of ASCVD in T2DM patients such as gender, age, HDL level, CT level, blood pressure, and
current smoking.

1. Introduction disease (ASCVD) [4]. In T2DM patients there is insulin resistance which
triggers hyperglycemia which causes multiple metabolic abnormalities
Cardiovascular disease (CVD) is the number one death for non- that increase the risk of ASCVD [5,6]. The gold-standard treatment for
communicable diseases each year globally. Around 17.9 million peo­ the prevention of primary and secondary ASCVD used statins [7] which
ple in the world die from this disease, and it is 31% of the causes of death statins have been shown to reduce the risk of CVD in T2DM [8]. This
worldwide [1]. Data from WHO shows that in Indonesia in 2012, study aimed to analyze the profile of the risk factors for ASCVD in T2DM
ischemic heart disease (IHD) placed second as the disease that can cause patients.
death in sufferers by 8.9% or around 138.4 thousand population, where
one of the main causes is atherosclerosis and diabetes [2]. Overall, an 2. Methods
estimated 2.6 million deaths are caused by elevated cholesterol and
another 29.7 million people experience disability each year. The prev­ 2.1. Participants
alence of coronary heart disease is 1.5% that increases with age, where
the highest group is at the age of 65–74 years [3]. Participants in this study were patients diagnosed with T2DM [9,10].
Diabetes mellitus is a metabolic disorder caused by genetic and Participant inclusion criteria included patients diagnosed with T2DM
environmental factors. Type 2 diabetes mellitus (T2DM) is a major risk (HbA1c of ≥6.5%, fasting plasma glucose of ≥126 mg/dL, 2-h plasma
factor affecting coronary artery disease (CAD) which approximately glucose & random plasma glucose ≥200 mg/dL) [11,12], and
75% of T2DM patients die as a consequence of atherosclerosis vascular consuming statins. Meanwhile, participant exclusion criteria included

* Corresponding author. Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga – Dr. Soetomo General Academic Hospital, Jl. Mayjend Prof.
Dr. Moestopo No. 6-8, Airlangga, Gubeng, Surabaya, East Java, 60286, Indonesia.
E-mail address: [email protected] (S.A. Soelistijo).

https://doi.org/10.1016/j.amsu.2022.103368
Received 17 December 2021; Received in revised form 4 February 2022; Accepted 10 February 2022
Available online 15 February 2022
2049-0801/© 2022 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Y.K. Ikhsan et al. Annals of Medicine and Surgery 75 (2022) 103368

patients with a history of CVD, patients who had received nicotinic acid was 205.19 ± 36.47 mg/dL, with a median value of 199.00
therapy, bile acid sequestrants, fibrates, ezetimibe, and PCSK9 in­ (178.00–225.25) mg/dL. The highest and lowest CT scores were 303.00
hibitors. Participants were required to fill out an informed consent mg/dL and 129 mg/dL, respectively. Most participants had CT values
before starting the study. ranging from 160.00 to 199.00 mg/dL as many as 53 participants
(42.7%). The participants’ average blood pressure was 123.98 ± 11.36
2.2. Study design mmHg, with a median value of 120.00 (120.00–130.00) mmHg. The
participants’ lowest and highest blood pressures were 100.00 mmHg
A cross-sectional study was conducted using purposive sampling and 181 mmHg, respectively. Most participants had blood pressure
from July 2020 to June 2021 with 124 T2DM patients. This study was ranging from 120.00 to 129.00 mmHg as many as 53 participants
conducted based on Strengthening the Reporting of Cohort Studies in (42.7%; Table 1).
Surgery (STROCSS) 2021 Guideline [13]. Measurement of ASCVD risk
score was calculated based on the Framingham score (FRS), of which the
calculation was based on ASCVD risk factors including age, TC, HDL, 4.2. Risk factor of atherosclerotic cardiovascular disease in type 2
blood pressure (systolic), current smoking, and diabetes [14]. The diabetes mellitus patient
measurement results were categorized into 3, namely low risk (<10%),
middle risk (11–19%), and high risk (≥20%). This measurement was The FRS participant measurement showed that 26 participants (21%)
used to predict that participants are likely to experience ASCVD disor­ had low risk of ASCVD, 52 participants (42%) had middle risk of ASCVD,
ders during the next 10 years [15]. and 46 participants (37%) had high risk of ASCVD. Based on the anal­
ysis, several risk factors for ASCVD in T2DM patients were found,
2.3. Blood pressure examination including gender (t = 6.015; p < 0.001), age (t = 6.901; p < 0.001), HDL
level (t = 2.287; p = 0.024), CT level (t = 5.273; p < 0.001), blood
Blood pressure is a vital sign measured by a tensimeter that is used to pressure (t = 5.850; p < 0.001), and current smoking (t = 2.638; p =
make a clinical decision. It is divided into two, systolic and diastolic, 0.009; Table 2). There was a significant relationship between ASCVD
with a measurement unit of mmHg. Blood pressure used in this study risk factor and ASCVD risk level (F = 36,642; p < 0.001).
was only systolic, which are categorized into hypertension (>140
mmHg), normal (100–140 mmHg), and hypotension (systolic <100 5. Discussion
mmHg) [16]. The categorization of blood pressure used in this study was
<120 mmHg, 120-29 mmHg, 130–139 mmHg, 140–149 mmHg, Age is a risk factor for ASCVD because increasing age will increase
150–159 mmHg, and ≥160 mmHg. the risk of atherosclerotic cardiovascular disease [19]. Age is a risk

3. Cholesterol examination Table 1

Characteristic of participant.
Cholesterol levels in this study were measured using a chemical auto- Variable n (%)
analyzer (Toshiba, Japan) [17], in which the cholesterol used in this
Gender
study included TC and HDL cholesterol [18]. Measurement of TC in this Male 39 (31.4)
study was in mg/dL, which was categorized into <160 mg/dL, 160–199 Female 85 (68.5)
mg/dL, 200–239 mg/dL, 240–279 mg/dL, and ≥280 mg/dL. Mean­ Age (years old)
while, HDL level measurements were categorized as follows <35 mg/dL, 30-34 3 (2.4)
35-39 3 (2.4)
35–44 mg/dL, 45–49 mg/dL, 50–59 dL, and 60 mg/dL. 40-44 6 (4.8)
45-49 14 (11.2)
3.1. Statistical analysis 50-54 27 (21.7)
55-59 23 (18.5)
60-64 22 (17.7)
The measurement data were collected and analyzed using the sta­
65-69 22 (17.7)
tistical package for the social science (SPSS) version 24.0 software (IBM 70-74 3 (2.4)
Corp., Armonk, NY, USA). The data were presented in the form of tables >75 1 (0.8)
or figures. Analysis to determine the risk factors for ASCVD in patients HDL level (mg/dL)
with diabetes mellitus used the ANOVA test which was declared sig­ <35 1 (0.8)
35-44 25 (20.1)
nificant if p < 0.05. In addition, this study used multiple linear regres­ 45-49 24 (19.3)
sion with p < 0.05. 50-59 37 (29.8)
≥60 37 (29.8)
4. Results Cholesterol total (mg/dL)
<160 10 (8.0)
160-199 53 (42.7)
4.1. Characteristic of participant 200-239 37 (29.8)
240-279 22 (17.7)
Most participants were female as many as 85 participants (65.8%), ≥280 2 (1.6)
and all participants had T2DM. Most participants were non-smokers as Blood pressure (mmHg)
23 (18.5)
many as 89 participants (71.8%). The participants’ average age was
<120
120-129 53 (42.7)
56.15 ± 9.01, with a median value of 57.00 (51.00–62.25) years. The 130-139 41 (33.0)
youngest and oldest participants were 30 years old and 75 years old, 140-149 1 (0.8)
respectively. Most participants were in the age range of 50–54 years as 150-159 4 (3.2)
2 (1.6)
much as 27 participants (21.7%). The participants’ average HDL levels ≥160
Diabetes mellitus
were 56.43 ± 17.42 mg/dL, with a median value of 52.00 (45.00–61.00) Yes 124 (100.0)
mg/dL. The lowest and highest HDL levels were 34.00 mg/dL and No 0 (0.0)
124.00 mg/dL, respectively. Meanwhile, the participants’ HDL levels Current smoking
ranged from 50.00 to 59.00 mg/dL and 60.00 mg/dL, each of which has Yes 35 (28.2)
No 89 (71.8)
a total of 37 participants (29.8%). The participants’ average CT value

2
Y.K. Ikhsan et al. Annals of Medicine and Surgery 75 (2022) 103368

Table 2 factor for CAD as increasing age will increase the risk of CVD. The older
Risk factor of atherosclerotic cardiovascular disease in type 2 diabetes mellitus. the age, the greater the possibility of atheroma plaques sticking to the
FRS t p walls and disrupting blood flow to the tissues [20]. ASCVD is more
common in men than women as supported by previous research, stating
Low Middle High
that the majority of patients with ASCVD are men [21]. The latest study
Gender 6.015 <0.001** in Indonesia stated that ASCVD was found in men as much as 61% with a
Male 4 (10.2) 6 (15.3) 29
(74.3)
prevalence ratio of 2:1 between men and women [3].
Female 22 46 17 Lower HDL cholesterol levels are associated with a higher risk of
(25.8) (54.1) (20.0) cardiovascular disease. Several studies have also shown that people with
Age (years old) 6.901 <0.001** HDL levels of <35 mg/dL are more likely to experience ASCVD [18,22].
30–34 3 0 (0.0) 0 (0.0)
HDL will carry cholesterol from tissues including coronary arteries to be
(100.0)
35–39 1 (33.3) 2 (66.7) 0 (0.0) catabolized in the liver. The newly formed HDL from its precursors,
40–44 4 (66.7) 2 (33.3) 0 (0.0) namely apo a-1, apo a-2, and apo a-milano proteins, will attract
45–49 8 (57.1) 3 (21.4) 3 (21.4) cholesterol with the help of the ATP binding cassette transporter A1
50–54 5 (18.5) 15 7 (26.0) (ABCT A1) enzyme. This HDL cholesterol will later increase in size and
(55.5)
55–59 4 (17.4) 12 7 (30.4)
can attract more fat and cholesterol in the body for catabolism [23]. In
(52.1) addition, high CT levels lead to deposition, narrowing, and plaque in
60–64 1 (4.5) 8 (36.5) 13 blood vessels and increase the risk of ASCVD [18,24]. Hypertension is a
(59.0) major risk factor contributing to ASCVD, which has been mentioned in
65–69 0 (0.0) 10 12
several kinds of literature and studies [25]. Recent studies have also
(45.5) (54.5)
70–74 0 (0.0) 0 (0.0) 3 stated that patients with hypertension have a 10 times risk of developing
(100.0) ASCVD including coronary heart disease [26].
>75 0 (0.0) 0 (0.0) 1 Meanwhile, current smoking increases the risk of ASCVD which
(100.0) mechanisms that cause atherosclerosis are direct endothelial injury due
HDL level (mg/dL) 2.287 0.024*
<35 0 (0.0) 0 (0.0) 1 (100)
to agents in cigarettes such as carbon monoxide and nicotine that cause
35–44 3 (12.0) 7 (28.0) 15 blebs on the lumen surface, microphile formation, and release of
(60.0) endothelial cells (endothelial damage), changes in platelets, increased
45–49 5 (20.8) 10 9 (37.5) fibrinogen and C-reactive protein levels and induce proinflammatory
(41.6)
cytokines [27]. Type 2 DM is a disease related to glucose in the blood, in
50–59 9 (24.3) 16 12
(43.2) (32.4) which when hyperglycemia occurs, the blood will experience a viscosity
≥60 9 (24.3) 19 9 (24.3) so that the blood supply to the tissue is blocked and has a high risk of
(51.3) ASCVD [2].
Cholesterol total (mg/ 5.273 <0.001** Nevertheless, this study has a limitation as it only included data
dL)
<160 3 (30.0) 3 (30.0) 4 (40)
components of the Framingham risk scoring risk factors such as gender,
160–199 17 22 14 age, HDL cholesterol levels, total cholesterol levels, blood pressure, type
(32.0) (41.6) (26.4) 2 diabetes mellitus status, and smoking status. Data such as body weight,
200–239 6 (16.2) 17 14 family history, low-density lipoprotein cholesterol levels, triglyceride
(46.0) (37.8)
levels, and physical activity were not included in this study. In addition,
240–279 0 (0.0) 9 (41.0) 13
(59.0) the method used was FRS, in which the score is only based on data from
≥280 0 (0.0) 1 (50.0) 1 (50.0) the white population. These considerations are expected to become an
Blood pressure 5.850 <0.001** evaluation for further research.
(mmHg)
13 7 (30.5) 3 (13.0)
6. Conclusion
<120
(56.5)
120–129 8 (15.0) 25 20
(47.1) (37.7) Based on the results of the patients’ risk score, the highest percentage
130–139 5 (21.1) 20 16 of atherosclerotic cardiovascular disease risk using FRS is patients with a
(48.7) (39.0)
moderate-risk level, followed by a high-risk level and a low-risk level.
140–149 0 (0.0) 0 (0.0) 1
(100.0) The analysis shows that T2DM participants are at risk for ASCVD that is
150–159 0 (0.0) 0 (0.0) 4 influenced by gender, age, current smoking, diabetes, blood pressure,
(100.0) HDL cholesterol, and TC.
≥160 0 (0.0) 0 (0.0) 2
(100.0)
Diabetes mellitus – –
Ethical approval
Yes 26 52 46
(21.0) (42.0) (37.0) We have conducted an ethical approval based on the Declaration of
No 0 (0.0) 0 (0.0) 0 (0.0) Helsinki with registration research at the Health Research Ethics Com­
Current smoking 2.638 0.009*
mittee in Dr. Soetomo General Academic Hospital, Surabaya, Indonesia.
Yes 5 (14.3) 7 (20.0) 23
(65.7)
No 21 45 23 Funding
(23.5) (50.5) (26.0)

Note: FRS = Framingham risk score; HDL = high-density lipoprotein; *signifi­ None.
cant <0.05; **significant <0.001.
Author contributor

All authors contributed toward data analysis, drafting and revising

the paper, gave final approval of the version to be published and agree to
be accountable for all aspects of the work.

3
Y.K. Ikhsan et al. Annals of Medicine and Surgery 75 (2022) 103368

Registration of research studies [7] U. Galicia-Garcia, S. Jebari, A. Larrea-Sebal, K.B. Uribe, H. Siddiqi, H. Ostolaza, et
al., Statin treatment-induced development of type 2 diabetes: from clinical
evidence to mechanistic insights, Int. J. Mol. Sci. 21 (13) (2020), https://doi.org/
Name of the registry: Health Research Ethics Committee in the Dr. 10.3390/ijms21134725.
Soetomo General Academic Hospital, Surabaya, Indonesia. [8] K.C. Maki, V. Diwadkar-Navsariwala, M.W. Kramer, Statin use and risk for type 2
Unique identifying number or registration ID: 0181/LOE/301.4.2/ diabetes: what clinicians should know, PGM (Postgrad. Med.) 130 (2) (2018)
166–172, https://doi.org/10.1080/00325481.2018.1402658.
XI/2020. [9] A.B. Pulungan, I.T. Afifa, D. Annisa, Type 2 diabetes mellitus in children and
Hyperlink to your specific registration (must be publicly accessible adolescent: an Indonesian perspective, Ann Pediatr Endocrinol Metabol 23 (3)
and will be checked): . (2018) 119–125, https://doi.org/10.6065/apem.2018.23.3.119.
[10] D. Ardiany, A. Pranoto, S.A. Soelistijo, Widjaja SA. Libriansyah, Association
between neutrophil–lymphocyte ratio on arterial stiffness in type-2 diabetes
Guarantor mellitus patients: a part of DiORS Study, Int. J. Diabetes Dev. Ctries. (2021),
https://doi.org/10.1007/s13410-021-00965-1.
[11] K. Pippitt, M. Li, H.E. Gurgle, Diabetes mellitus: screening and diagnosis, Am. Fam.
Soebagijo Adi Soelistijo. Physician 93 (2) (2016) 103–109.
[12] A. Kumar, T. Kumar, M. Bhargava, R. Raj, V. Vaibhav, J. Kishore, Salivary and
Consent serum glucose levels in diabetes mellitus patients versus control - a randomised
control trial, J Med life 13 (2) (2020) 235–240, https://doi.org/10.25122/jml-
2020-0062.
Written informed consent was obtained from the patient. [13] G. Mathew, R. Agha, Strocss 2021: Strengthening the reporting of cohort, cross-
sectional and case-control studies in surgery, Int. J. Surg. 96 (2021) 106165,
https://doi.org/10.1016/j.ijsu.2021.106165.
Provenance and peer review
[14] C.A. Schulz, L. Mavarani, N. Reinsch, S. Albayrak-Rena, A. Potthoff,
N. Brockmeyer, et al., Prediction of future cardiovascular events by Framingham,
Not commissioned, externally peer-reviewed. SCORE and asCVD risk scores is less accurate in HIV-positive individuals from the
HIV-HEART Study compared with the general population, HIV Med. 22 (8) (2021)
732–741, https://doi.org/10.1111/hiv.13124.
Declaration of competing interest [15] W. Weng, Y. Tian, S.X. Kong, R. Ganguly, M. Hersloev, J. Brett, et al., Impact of
atherosclerotic cardiovascular disease on healthcare resource utilization and costs
The authors declare no conflict of interest. in patients with type 2 diabetes mellitus in a real-world setting, Clin Diabetes
Endocrinol 6 (2020) 5, https://doi.org/10.1186/s40842-019-0090-y.
[16] A. Herbert, J.K. Cruickshank, S. Laurent, P. Boutouyrie, Establishing reference
Acknowledgment values for central blood pressure and its amplification in a general healthy
population and according to cardiovascular risk factors, Eur. Heart J. 35 (44)
(2014) 3122–3133, https://doi.org/10.1093/eurheartj/ehu293.
We thank our editor “Fis Citra Ariyanto”. [17] A. Ozder, Lipid profile abnormalities seen in T2DM patients in primary healthcare
in Turkey: a cross-sectional study, Lipids Health Dis. 13 (2014) 183, https://doi.
Abbreviations org/10.1186/1476-511x-13-183.
[18] D.M. Maahs, A.K. Maniatis, K. Nadeau, R.P. Wadwa, K. McFann, G.J. Klingensmith,
Total cholesterol and high-density lipoprotein levels in pediatric subjects with type
ASCVD atherosclerosis vascular disease 1 diabetes mellitus, J. Pediatr. 147 (4) (2005) 544–546, https://doi.org/10.1016/j.
ABCT A1 ATP binding cassette transporter A1 jpeds.2005.04.068.
[19] T. Head, S. Daunert, P.J. Goldschmidt-Clermont, The aging risk and
CAD coronary artery disease
atherosclerosis: a fresh look at arterial homeostasis, Front. Genet. 8 (2017) 216,
CVD Cardiovascular disease https://doi.org/10.3389/fgene.2017.00216.
FRS Framingham Risk Score [20] Y. Yang, J. Tian, C. Zeng, J. Wei, L.J. Li, X. Xie, et al., Relationship between
HDL high-density lipoprotein hyperuricemia and risk of coronary heart disease in a middle-aged and elderly
Chinese population, J. Int. Med. Res. 45 (1) (2017) 254–260, https://doi.org/
IHD ischemic heart disease 10.1177/0300060516673923.
LDL low-density lipoprotein [21] M. Rafieian-Kopaei, M. Setorki, M. Doudi, A. Baradaran, H. Nasri, Atherosclerosis:
STROCSS Strengthening the Reporting of Cohort Studies in Surgery process, indicators, risk factors and new hopes, Int. J. Prev. Med. 5 (8) (2014)
927–946.
T2DM type 2 diabetes mellitus [22] L. Badimon, G. Vilahur, LDL-cholesterol versus HDL-cholesterol in the
TC total cholesterol atherosclerotic plaque: inflammatory resolution versus thrombotic chaos, Ann. N.
Y. Acad. Sci. 1254 (2012) 18–32, https://doi.org/10.1111/j.1749-
6632.2012.06480.x.
References [23] H.H. Wang, G. Garruti, M. Liu, P. Portincasa, D.Q. Wang, Cholesterol and
lipoprotein metabolism and atherosclerosis: recent advances in reverse cholesterol
[1] W. Hinton, A. McGovern, R. Coyle, T.S. Han, P. Sharma, A. Correa, et al., Incidence transport, Ann. Hepatol. 16 (Suppl. 1) (2017) s27–s42, https://doi.org/10.5604/
and prevalence of cardiovascular disease in English primary care: a cross-sectional 01.3001.0010.5495, s3-105.
and follow-up study of the Royal College of General Practitioners (RCGP) Research [24] R. Quispe, M.B. Elshazly, D. Zhao, P.P. Toth, R. Puri, S.S. Virani, et al., Total
and Surveillance Centre (RSC), BMJ Open 8 (8) (2018), e020282, https://doi.org/ cholesterol/HDL-cholesterol ratio discordance with LDL-cholesterol and non-HDL-
10.1136/bmjopen-2017-020282. cholesterol and incidence of atherosclerotic cardiovascular disease in primary
[2] A. Crisafulli, P. Pagliaro, S. Roberto, L. Cugusi, G. Mercuro, A. Lazou, et al., prevention: the ARIC study, Eur J Prev Cardiol 27 (15) (2020) 1597–1605, https://
Diabetic cardiomyopathy and ischemic heart disease: prevention and therapy by doi.org/10.1177/2047487319862401.
exercise and conditioning, Int. J. Mol. Sci. 21 (8) (2020), https://doi.org/10.3390/ [25] R. Nakanishi, L. Baskaran, H. Gransar, M.J. Budoff, S. Achenbach, M. Al-Mallah, et
ijms21082896. al., Relationship of hypertension to coronary atherosclerosis and cardiac events in
[3] A. Maharani, Sujarwoto, D. Praveen, D. Oceandy, G. Tampubolon, A. Patel, patients with coronary computed tomographic angiography, Hypertension (Dallas,
Cardiovascular disease risk factor prevalence and estimated 10-year cardiovascular Tex : 1979) 70 (2) (2017) 293–299, https://doi.org/10.1161/
risk scores in Indonesia: the SMARThealth Extend study, PLoS One 14 (4) (2019), hypertensionaha.117.09402.
e0215219, https://doi.org/10.1371/journal.pone.0215219. [26] Y. Zhou, R. Zhang, G. Wang, A. Wang, C. Zhong, M. Zhang, et al., Coexistence
[4] R. Naito, K. Miyauchi, Coronary artery disease and type 2 diabetes mellitus, Int. effect of hypertension and angiotensin II on the risk of coronary heart disease: a
Heart J. 58 (4) (2017) 475–480, https://doi.org/10.1536/ihj.17-191. population-based prospective cohort study among Inner Mongolians in China,
[5] S. De Rosa, B. Arcidiacono, E. Chiefari, A. Brunetti, C. Indolfi, D.P. Foti, Type 2 Curr. Med. Res. Opin. 35 (8) (2019) 1473–1478, https://doi.org/10.1080/
diabetes mellitus and cardiovascular disease: genetic and epigenetic links, Front. 03007995.2019.1601430.
Endocrinol. 9 (2018) 2, https://doi.org/10.3389/fendo.2018.00002. [27] G. Siasos, V. Tsigkou, E. Kokkou, E. Oikonomou, M. Vavuranakis, C. Vlachopoulos,
[6] M.A. Abdul-Ghani, A. Jayyousi, R.A. DeFronzo, N. Asaad, J. Al-Suwaidi, Insulin et al., Smoking and atherosclerosis: mechanisms of disease and new therapeutic
resistance the link between T2DM and CVD: basic mechanisms and clinical approaches, Curr. Med. Chem. 21 (34) (2014) 3936–3948, https://doi.org/
implications, Curr. Vasc. Pharmacol. 17 (2) (2019) 153–163, https://doi.org/ 10.2174/092986732134141015161539.
10.2174/1570161115666171010115119.