Einarson 2018

Einarson
et al. Cardiovasc Diabetol (2018) 17:83

https://doi.org/10.1186/s12933-018-0728-6 Cardiovascular Diabetology
REVIEW Open Access
Prevalence of cardiovascular disease

in type 2 diabetes: a systematic literature review
of scientific evidence from across the world
in 2007–2017
Thomas R. Einarson1^, Annabel Acs2, Craig Ludwig2* and Ulrik H. Panton3
Abstract
Background: Cardiovascular disease (CVD) is a common comorbidity in type 2 diabetes (T2DM). CVD’s prevalence
has been growing over time.
Purpose: To estimate the current prevalence of CVD among adults with T2DM by reviewing literature published
within the last 10 years (2007–March 2017).
Methods: We searched Medline, Embase, and proceedings of major scientific meetings for original research docu‑
menting the prevalence of CVD in T2DM. CVD included stroke, myocardial infarction, angina pectoris, heart failure,
ischemic heart disease, cardiovascular disease, coronary heart disease, atherosclerosis, and cardiovascular death. No
restrictions were placed on country of origin or publication language. Two reviewers independently searched for
articles and extracted data, adjudicating results through consensus. Data were summarized descriptively. Risk of bias
was examined by applying the STROBE checklist.
Results: We analyzed data from 57 articles with 4,549,481 persons having T2DM. Europe produced the most articles
(46%), followed by the Western Pacific/China (21%), and North America (13%). Overall in 4,549,481 persons with T2DM,
52.0% were male, 47.0% were obese, aged 63.6 ± 6.9 years old, with T2DM duration of 10.4 ± 3.7 years. CVD affected
32.2% overall (53 studies, N = 4,289,140); 29.1% had atherosclerosis (4 studies, N = 1153), 21.2% had coronary heart
disease (42 articles, N = 3,833,200), 14.9% heart failure (14 studies, N = 601,154), 14.6% angina (4 studies, N = 354,743),
10.0% myocardial infarction (13 studies, N = 3,518,833) and 7.6% stroke (39 studies, N = 3,901,505). CVD was the cause
of death in 9.9% of T2DM patients (representing 50.3% of all deaths). Risk of bias was low; 80 ± 12% of STROBE check‑
list items were adequately addressed.
Conclusions: Globally, overall CVD affects approximately 32.2% of all persons with T2DM. CVD is a major cause of
mortality among people with T2DM, accounting for approximately half of all deaths over the study period. Coronary
artery disease and stroke were the major contributors.
Keywords: Cardiovascular disease, Type 2 diabetes, Prevalence, Stroke, Ischemic heart disease, Myocardial infarction,
Angina
*Correspondence: cl@last‑mile.dk
^
Deceased
2
Last Mile, Holte, Denmark
Full list of author information is available at the end of the article
© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium,
provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/
publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Einarson et al. Cardiovasc Diabetol (2018) 17:83 Page 2 of 19
Background macrovascular complications appears to be multifacto-

The International Diabetes Federation (IDF) estimates rial risk factor reduction (glycemic control, smoking ces-
that worldwide, 415 million people have diabetes, 91% of sation, diet, exercise, aggressive blood pressure control,
whom have type 2 diabetes mellitus (T2DM) [1]. People treatment of dyslipidemia).
with diabetes comprise 8.8% of the world’s population, As a result, diabetes treatment guidelines have been
and IDF predicts that the number of cases of diabetes will updated to provide guidance on how to prevent and
rise to 642 million by 2040 [1]. The prevalence of T2DM manage the onset of CVD [14]. Furthermore, there is
has been steadily increasing over time. Using data from increasing pressure from regulatory agencies that antidi-
the Framingham Heart Study, Abraham et al. [2] noted abetic treatments demonstrate cardiovascular safety and
that the overall annualized incidence rates of the disease benefits, especially for major cardiovascular events such
per 1000 persons increased from 3.0 in the 1970s to 5.5 as cardiovascular mortality, non-fatal MI, and stroke
in the first decade of the 2000s. That change represented [15, 16]. Following these regulatory requirements, sev-
an increase in the incidence of T2DM of 83.3% and was eral cardiovascular outcomes trials (CVOT) have been
higher in males than females by a factor of 1.61. completed, which demonstrate that certain anti-diabetic
Cardiovascular disease (CVD) is a major cause of death treatments are associated with a lower risk of CVD
and disability among people with diabetes [1, 3]. Adults [17–20].
with diabetes historically have a higher prevalence rate The increased focus on adequately treating patients
of CVD than adults without diabetes [4], and the risk of with both CVD and T2DM requires that we have
CVD increases continuously with rising fasting plasma updated prevalence rates of CVD among patients with
glucose levels, even before reaching levels sufficient for a T2DM. This is especially needed to inform clinical and
diabetes diagnosis [5]. policy level decision-making by healthcare providers,
T2DM reduces life expectancy by as much as 10 years, healthcare policy decision-makers, and health economic
and the main cause of death for patients with T2DM is analysts. Reviews have been published on the epidemiol-
CVD [1, 3]. Furthermore, people with T2DM are dis- ogy of type 1 diabetes (T1DM), and CVD [21], pre-dia-
proportionately affected by CVD compared with non- betes and the risk of CVD [22], or reviews have focused
diabetic subjects [6]. Haffner et al. [6] reported death on specific countries [23]. However, there is no recent
rates due to cardiovascular causes over a 7-year period global review on the prevalence of CVD among adults
in patients with and without T2DM. In persons with with T2DM. Therefore, the objective of this systematic
T2DM, the death rates were 15.4% for those with no literature review was to quantitatively summarize rates of
prior myocardial infarction (MI) and 42.0% in patients prevalence of CVD in adults with T2DM in studies pub-
having a history of MI. In contrast, patients who did not lished during the past 10 years.
have T2DM, the death rates due to cardiovascular causes Although CVD is an umbrella term that includes cor-
were 2.1 and 15.9%, respectively. onary artery disease (CAD), cerebrovascular disease
In the Framingham Heart Study, Fox [7] reported that, (CBV), and peripheral vascular disease, the focus of this
along with the increasing T2DM prevalence, the attrib- review was on CVD outcomes that are relevant to major
utable risk of CVD due to T2DM increased from 5.4% cardiovascular events. Therefore, the review specifically
in the period 1952–1974 to 8.7% in the period 1975 focused on the prevalence of CAD and CBV. CAD has
and 1998. In a longitudinal study of 881 patients with many synonyms, including ischemic heart disease, coro-
T2DM over 10 years, van Hateren et al. [8] indicated that nary heart disease (CHD), atherosclerotic heart disease,
the hazard ratio for death due to CVD was constantly and atherosclerotic CVD. Conditions within this category
increasing each year. Thus, an increasing burden of dia- are stable angina pectoris, unstable angina pectoris, MI
betes will likely be followed by an increasing burden of (also known as heart attack), and sudden cardiac death
CVD. (SCD). CBV comprises mainly stroke (intracerebral hem-
Given the clinical burden that CVD complications have orrhage, cerebral infarction, cerebral arterial disease), but
on T2DM patients, there has been an increased focus on also may include transient ischemic attacks.
the joint management of T2DM and CVD. Good glyce-
mic control remains the main foundation for managing Methods
T2DM. Although the importance of intensive glycemic This review was undertaken in adherence to the PRISMA
control for protection against microvascular complica- Statement for systematic reviews [24].
tions and CVD in people with T1DM is well established
[9, 10], its role for reducing cardiovascular risk has not Eligibility criteria
been established as clearly in people with T2DM [11–13]. Criteria for eligibility were guided by the PICO reporting
Hence, the most effective approach for prevention of system (which describes the participants, interventions,
comparisons, and outcome[s] of the systematic review), and Embase between January 2007 and March 2017. In
together with the specification of the type of study design addition, PubMed was searched from 2014 to identify
(PICOS), from the Preferred Reporting Items for System- articles that were “ahead of print” yet fully available. Evi-
atic Reviews and Meta-Analyses (PRISMA) [24]. dence presented at selected conferences during the last
5 years were accessed, including the Annual Meetings of
Participants the International Society Pharmacoeconomic Outcomes
Included in this research were adult patients ≥ 18 years and Research (ISPOR), American Diabetes Association
old who had been diagnosed with T2DM. (ADA), European Association for the Study of Diabetes
(EASD) and American Association of Clinical Endocri-
Interventions nologists (AACE). Keywords linked to MeSH terms spe-
Not applicable in this research. cific to each database were used in the search including
prevalence, OR epidemiology, AND acute coronary syn-
Comparisons drome, OR cardiovascular disease, OR cardiovascular
Prevalence rates of CVD between males and females, and death, OR non-fatal myocardial infarction, OR non-fatal
between obese and non-obese patients were compared. stroke, OR obesity AND type 2 diabetes mellitus. Other
It was acknowledged that, in the literature, authors often keywords were cerebrovascular disease, cerebral arterial
used different terms or combinations of terms to describe disease, intracerebral hemorrhage, cerebral infarction,
their patients. The aim was to be all-inclusive in order to coronary artery disease, ischemic heart disease, athero-
capture all relevant patient populations. Broad definitions sclerotic heart disease, coronary heart disease, angina
of acceptable diseases were CVD, CAD, CHD, ischemic pectoris. Identified articles and previous reviews were
heart disease (IHD), congestive heart failure (CHF), or hand searched for articles that may have included data
CBV. Specific conditions of interest included stroke, MI/ useful to this search.
heart attack, angina pectoris, heart failure, and athero-
sclerosis as well as cardiovascular or cardiac death. Article identification and selection
Excluded were other forms of CVD including periph- Two reviewers independently searched Medline, Embase
eral artery disease (PAD), rheumatic heart disease, car- and the proceedings of major scientific meetings for
diac dysrhythmias (e.g., atrial or ventricular fibrillation), suitable papers. Results were compared and adjudicated
or requirement for surgery such as coronary artery through consensus discussion. A third reviewer checked
bypass grafting (CABG)/coronary revascularization. all results for quality assurance.
Also excluded were intermediate states such as hyperten-
sion or metabolic syndrome or studies of carotid intima- Data collection
media thickness (CIMT). Data extracted from articles included information con-
cerning the publication, the patients involved, and out-
Outcome[s] comes of interest. Publication items included the first
The outcome of interest was the prevalence of each of author, year of publication, the country in which the
these diseases/outcomes, then aggregated by continent/ data were collected, and date of data collection. Patient
IDF Region, by country, and by the country’s economic data collected included the number of patients screened,
status. percentages of males and females, average age, duration
of T2DM, the proportion with obesity (or average body
Study design mass index (BMI) ± SD). Outcome data consisted of the
The primary focus was on prevalence studies and cross- numbers and percentages of patients having each cardio-
sectional surveys, including database studies or patient vascular outcome, overall and separately for males and
chart reviews. Incidence studies were accepted only if females, where available. The same procedure (two inde-
they provided population-based baseline and follow-up pendent reviewers plus a third judge) was followed for
data. Included were peer-reviewed studies published in data collection as for article selection.
any language. Both published articles and abstracts from
scientific meetings were eligible. However, any published Data analysis
studies from clinical trial programs or individual phar- Data were analyzed descriptively, with sums, averages,
maceutical products were excluded. and medians, and ranges reported. The primary outcome
was the estimate of prevalence rates of CVD in patients
Information sources and search strategy with T2DM. No overall quantitative synthesis was under-
The search was undertaken between February 15 and taken. Weighted averages were calculated for individual
March 6, 2017. Databases searched included Medline countries and IDF regions. For patient characteristics,
we calculated simple averages and medians across stud- presented in a list of recommendations. Items are scored
ies. Due to a single study with a sample size of more than as dichotomously as acceptable or not acceptable.
three million people, which skewed the data, we calcu-
lated weighted averages for patient characteristics with Results
and without that study. It should be noted that averages Included studies
were based on the studies that reported the outcome, The flowchart in Fig. 1 depicts the article selection pro-
which may then represent a subgroup of the entire pool cess. We initially identified 1539 papers that appeared to
of studies. be suitable, but after examining them systematically, 57
The risk of bias was explored by applying the checklist studies were accepted. Three articles each presented two
from the STROBE initiative [25]. They have produced a different sets of results [26–28]; therefore, there are 60
validated checklist of items that should be addressed in sets of analyses within these 57 articles. Table 1 lists these
reports of observational studies. There are 22 main items, studies along with their descriptive variables. There were
each of which addresses an issue of research design and is 51 full articles and six abstracts presented at scientific
Idenficaon
Records idenfied through Addional records idenfied

database searching through other sources
(n = 1,479) (n = 60)
)
Records aer duplicates removed

(n = 1,539)
Screening
Records screened Records excluded

(n = 1,539) (n = 1,373)
Full-text arcles assessed Full-text arcles excluded, with

for eligibility reasons (n = 109)
Eligibility
(n = 166) Reasons:
No outcomes of interest (n = 49)
Incidence study (n = 34)
T2DM not disaggregated (n = 9)
Duplicate (n = 5)
Review (n = 6)
Arcles included in this Inappropriate paents (n = 4)
review Predicve model (n = 2)
(n = 57)
Included
Fig. 1 Flowchart of article selection. The flowchart depicts the article selection process
Table 1 Overview of studies in the analysis

Author (year) Country Patients % obese % Age (years) Diabetes Follow-up Time of data
or reported BMI males duration (years) collection
(years)
Alaboud (2016) [41] Saudi Arabia 748 64.3% 42.4% 57.9 13.3 NR Apr–Jun 2014
Alonso-Moran Spain 134,421 NR 54.0% NR NR NR 2007–2011
(2014) [42]
Alwakeel (2008) [30] Saudi Arabia 1952 44.8% 48.3% 58.4 10.4 7.9 Jan 1989–Jan 2004
Bhatti (2016) [26]a India 1522 BMI = 26.7 ± 4.4 58.3% 58.1 7.2 NR 2011–2014
Boonman-de Winter Netherlands 581 28.1% 53.4% 71.6 5.5 NR Feb 2009–Mar 2010
(2012) [38]
Cardoso (2008) [31] Brazil 471 NR 34.2% 60.5 9.3 4.8 1994–1996, 2001
Carnethon (2010) USA 919 BMI = 28.2 ± 4.9 53.4% 72.8 NR 11.3 (1989/92–93)
[32] through 2005
Carrasco-Sánchez Spain 490 BMI = 31.4 ± 14.23 44.3% 76.6 NR NR 2008–2011
(2014) [43]
Cheng (2014) [86] China 2834 91.6% 51.8% 58.5 7.0 NR Aug 2011–Mar
2012
Collier (2015) [27]a Scotland 7385 51.0% NR 64.3 NR NR NR
6032 57.5% NR 66.4 NR NR NR
Cortez-Dias (2010) Portugal 3215 45.1% 38.4% 58.1 NR NR Apr 2006–Nov 2007
[87]
Daghash (2007) [88] Qatar 180 BMI = 30.35 ± 4.9 43.0% 51.3 NR NR May–Oct 2004
Doucet (2016) [89] France 987 BMI = 29.7 ± 5.2 47.9% 77.1 17.8 NR Jun 2009–Jul 2010
Eeg-Olofsson (2010) Sweden 18,334 BMI = 28.8 ± 5 56.7% 64.0 8.0 5.6 1997–1998–2003
[33]
Farrell (2014) [90] Ireland 309 NR NR NR NR NR NR
Fu (2010) [91] Spain, France, UK, 1942 52.9% 64.4% 64.5 6.2 2.8 Jun 2006–Feb 2007
Norway, Finland,
Germany, Poland
Giallauria (2015) [92] Italy 475 NR 74% 69.7 NR NR Jan 28–Feb 10,
2008
Glogner (2014) [40] Sweden 83,021 BMI = 28.9 ± 5.04 55.3% 65.8 7.6 7.2 Enrolled: 1998–
2003; through
2009
Gobardhan (2017) Netherlands 318 53.0% 50.9% 52.3 11.0 10.0 NR
[93]
Gondim (2016) [94] Brazil 66 BMI = 27.17 ± 4.62 43.9% 64.6 NR NR NR
Hermans (2016) [95] Belgium 711 BMI = 29.5 ± 5.8 66% 67.0 16.0 NR NR
Hunt (2014) [96] USA 1030 BMI = 33.6 23.5% 52.7 10.5 NR 1995–2003
Jackson (2012) [97] Scotland 216,652 NR 53.6% ≥40 NR 4.5 2001–2007
Jurado (2009) [98] Spain 307 44.9% 61.6% 59.6 8.5 NR Nov 2001–Dec
2002
Kucharska-Newton USA 209 BMI = 31.0 ± 6.0 43.5% 55.5 NR NR 1987–1989–2001
(2010) [99]
Kwon (2014) [100] Korea 59 NR 59.3% 64.5 NR 13.0 Korea
Lin (2013) [45] USA 162,332 NR NR ≥18 ≥2 ≥2 USA
Liu (2015) [101] China 21,072 NR 53.9% 63.7 NR NR China
Luo (2014) [102] China 4836 BMI: 24.3 57.6% 64.9 NR 1.0 China
MacDonald (2011) 247 countries 669 BMI = 31.2 ± 4.6 51.7% 58.8 7.2 2.0 247 countries
[103]
Malik (2015) [34] Scotland 121,523 BMI = 31.7 ± 6.6 52.0% 63.0 4.2 4.8 Scotland
Mansour (2013) [48] Iraq 1079 33.8% 58.8% 56.3 7.4 NR Iraq
Mazza (2007) [104] Italy 581 30.1% 34.8% 74.3 20.3 12.0 Italy
Menghua (2014) China 240 NR NR NR NR NR China
[49]
Table 1 (continued)
Author (year) Country Patients % obese % Age (years) Diabetes Follow-up Time of data
or reported BMI males duration (years) collection
(years)
Menzaghi (2014) Italy 2094 BMI = 29.1 ± 5.3 51.3% 61.9 10.4 12.9 Italy
[36]
Mody (2007) [105] USA 4816 NR 34.4% 50.9 NR NR USA
Mundet (2012) [106] Spain 4298 BMI = 29.34 ± 4.84 48.2% 67.4 8.4 10.0 Spain
Narksawat (2013) Thailand 1505 32.2% 30.4% 63.3 NR NR Thailand
[107]
Norhammar (2016) Sweden 352,436 NR 56.1% 67.1 NR NR Sweden
[50]
Penno (2015) [108] Italy 11,538 34.5% 52.9% 65.5 12.5 NR Italy
Rodriguez-Poncelas Spain 1141 46.5% 60.6% 66.8 9.1 NR Feb–Jul 2011
(2014) [109]
Rossi (2011) [51] Italy 5181 BMI = 29.8 ± 5.0 58.4% 64.4 10.0 2.3 (Jan 2006–Nov
2007), 2009
Salinero-Fort (2016) Spain 3407 BMI = 30.1 ± 4.9 50.3% 69.0 9.1 5.0 2007 (2008–2012)
[35]
Senthil (2014) [69] India 134 NR 72.1% NR NR NR NR
Shestakova (2016) Russian Federation 3,060,517 NR 28.3% NR NR 1.0 2014–2015
[29]
Soetedjo (2014) Indonesia 400 56.8% 43.8% 57.7 10.3 NR Dec 2013–Jun 2014
[110]
Song (2009) [46] UK 2733 BMI = 33.4 ± 6.7 NR 64.2 12.7 NR 2008
Suh (2008) [111] USA 608 51.4% 44.82% 73.2 12.9 10.0 1999–2004
Tamba (2013) [37] Cameroon 132 30.0% 56% 58.0 12.0 6.0 2000–2009
Tan (2016) [28]a Australia 793 54.8% 50.9% 67.2 8.0 15.0 2008–2011
65 35.4% 56.9% 61.1 10.0 15.0
Utrera-Lagunas Mexico 160 33.8% 45.0% 69.2 18.3 NR Feb 2011–Jan 2012
(2013) [112]
Vinagre (2012) [113] Spain 286,791 45.4% 53.7% 68.2 6.5 NR 2009
Wentworth (2012) Australia 711 >50% 55.1% 53.0 11.4 NR 1998–2011
[39]
Wong (2012) [114] USA 889 NR 46.2% 60.6 13.3 NR 2003–2006
Yan (2015) [115] Hong Kong 10,952 63.6% 56.1% 58.2 7.0 NR Nov 2007–Jul 2012
Yang (2015) [47] Korea 595 BMI = 24.29 ± 3.15 58.32% 64.9 13.6 NR 2006–2010
Zekry (2012) [116] Switzerland 83 BMI = 27.2 ± 4.9 36.1% 84.2 NR 4.0 Jan 2004–Dec 2005
57 studies Total 4549,481
Median 1030 45.4% 52.0% 64.3 10.0 6.0
Average 77,110 47.0% 50.5% 63.6 10.4 7.3
SD (range) (59–3,060,517) 14.7% 10.3% 6.9 3.7 4.5
BMI body mass index, NR not reported, SD standard deviation

a
Study reports two separate analyses within the same paper; thus, there are 60 studies in 57 articles
meetings. Data collectively represent more than 4.5 mil- Arabia, Scotland, Spain, Sweden, Switzerland, Thailand,
lion people with T2DM from around the globe. UK and USA. Details are provided in Table 3. Three
In Table 2, results are presented geographically accord- areas were responsible for generating 80% of the stud-
ing to the classification system used by the IDF [1]. Stud- ies. Europe produced most articles (46%), followed by the
ies from 25 countries were represented in this review: Western Pacific/China (21%), and North America (13%).
Australia, Belgium, Brazil, Cameroon, China, France, The other 20% were from the rest of the world. There
India, Indonesia, Iraq, Ireland, Italy, Korea, Mexico, were no discernible patterns differentiating prevalence
Netherlands, Portugal, Qatar, Russian Federation, Saudi rates between countries, based on income status. Part of
the problem is that there are few studies in low- and mid- T2DM nor CVD, the odds ratio for death was 4.56 (95%
dle-income countries and none from those in the lowest CI 3.53–5.89) [32]. Using a weighted average from seven
income level. studies (N = 86,557) [29–35], the calculated deaths due to
CVD comprised 50.3% (95% CI 37.0–63.7%) of all deaths
Patient characteristics in patients with T2DM. The major contributors were
In the 57 individual studies, data from 4.5 million peo- CAD, which was responsible for 29.7% (95% CI 25.1–
ple with T2DM were presented with nearly 3.1 mil- 34.4%) and stroke/CBV for 11.0% (95% CI 8.8–13.3%).
lion people coming from a single Russian study by
Shestakova [29]. As presented in Table 1, using a CVD among obese vs. non‑obese people with T2DM
simple average across studies, the average age was About half of the patients included in this analysis had
63.6 ± 6.9 (median = 64.3 years; weighted aver- obesity. Three-quarters of the included studies reported
age = 66.3 ± 6.9 years). The weighted average proportion on patients’ BMI or the percent of patients with obesity.
of persons with obesity was 46.3 ± 15.0%, with a sim- While the definitions and BMI cut-off points of obesity
ple average of 47.0 ± 14.7% (median = 45.4%), defined varied across studies, the most commonly used definition
as a BMI ≥ 30 kg/m2. The mean percentage of males of obesity was a BMI ≥ 30 kg/m2, which was employed by
across the studies was 50.5 ± 10.3% (median = 52.0%); 16 studies (43% of those providing a definition).
the weighted average of the proportion of males was Five papers reported prevalence rates of CVD
36.0 ± 10.0%, including the study by Shestakova [29], according to obesity status, and all of them found a
and 54.1 ± 9.9% excluding that study. The patients positive relationship between obesity and increased
had T2DM for an average duration of 10.4 ± 3.7 years prevalence rates of CVD [26, 37–40]. Using logistic
(median = 10.0 years; weighted average = 6.6 ± 3.7 years). regression to control for multiple factors, Bhatti et al.
Among the 23 studies that reported duration of follow- [26] found a positive correlation between obesity and
up, the average was 7.3% ± 4.5 years (median = 6.0 years; CAD (P = 0.021). Tamba et al. [37] reported positive
weighted average = 5.2 ± 4.3 years). correlations between obesity and both CAD (r = 0.3,
Prevalence rates of cardiovascular comorbidities are P < 0.001) and stroke (r = 0.5, P < 0.001). Boonman-de
summarized in Table 4 for all patients as well as sepa- Winter et al. [38] quantified the relationship between
rately for males and females. In studies reporting gender- BMI and heart failure. The prevalence rate of heart fail-
specific prevalence rates, males had higher prevalence ure was 38.7% (95% CI 31.2–46.1%) in patients with a
rates than females for all outcomes except overall CVD, BMI ≥ 30 kg/m2 and 23.4% (95% CI 19.4–27.5%) in
where both sexes had an overall prevalence rate of those with a BMI < 30 kg/m2, which represents a 65%
approximately 27%. Overall, in studies that presented increase due to obesity.
prevalence rates for males and females combined, the Two studies explored the relationship between increas-
prevalence of CVD among persons with T2DM was ing BMI and risk of CVD [39, 40]. According to Went-
32.2%. CAD and atherosclerosis were the most prevalent worth et al. [39], for CAD in both males and females, the
CVD comorbidities, with prevalence rates of 21.2 and prevalence rate of CAD increased with each successive
29.1%, respectively, whereas stroke was the least preva- increase in BMI, with a five-fold increase between the
lent with a prevalence rate of 7.6%. It is unclear why peo- lowest and highest categories [< 25 (normal), 25–30 kg/
ple with T2DM have different susceptibilities to these m2 (overweight), 30–35 kg/m2 (mild obesity), 35–40 kg/
diseases. An explanation for the high prevalence rate for m2 (moderate obesity) and > 40 kg/m2 (severe obe-
atherosclerosis could be that it is an artifact of patient sity)]. The difference was that prevalence rates in males
selection. In the studies that examined atherosclerosis, were about double those for females in every BMI cat-
most patients were enrolled if they had high-risk scores egory. For the outcome stroke/transient ischemic attack
for atherosclerosis, resulting in a very high rate of disease (TIA) in males, only the highest category (BMI > 40)
detection. had elevated prevalence rates, which were about double
those for the lowest category (BMI < 25). For females,
CVD mortality among patients with T2DM prevalence rates of stroke/TIA increased in those who
Table 5 presents the data regarding the rates of mortal- were overweight and had mild or moderate obesity but
ity associated with CVD in persons with T2DM. The decreased for those with severe obesity. Finally, Glog-
weighted average of death rates from the eight studies ner et al. [40] had quite different results. They reported
with 3,208,557 patients with T2DM was 9.9% (95% CI a steady increase in prevalence rates of MI from 6.86%
8.6–11.3%) [29–36]. There were 6.3% who died due to in those with a BMI < 20–9.33% in patients who were
CAD and another 1.5% from CBV. Comparing patients overweight (BMI 25–30), a 36% increase. However, MI
with both T2DM and CVD with patients having neither prevalence rates declined thereafter with each increasing
Table 2 Geographic distribution of prevalence studies of cardiovascular disease in type 2 diabetes mellitus
Einarson et al. Cardiovasc Diabetol (2018) 17:83
Region Populationa Studies N Stroke (%) MI Angina Heart failure Atherosclerosis CAD CVD (%)
(millions)
Africa 441 1 132 5.0 NR NR NR NR 23.6% 28.6

Europe 660 29b 4,327,503 7.2 10.0% 14.6% 19.0% 33.0% 15.4% 30.0
Middle East and North Africa 387 4 3959 7.1 11.4% NR NR NR 27.4% 26.9
North America and Caribbean 344 8 170,963 10.9 13.6% 17.2% 29.5% NR 20.1% 46.0
South and Central America 315 2 537 5.5 NR NR 4.2% NR 22.6% 27.5
Southeast Asia 926 3b 1656 3.1 NR NR NR NR 29.4% 42.5
Western Pacific (includes China) 1600 12b 44,062 11.4 NR NR 4.3% 26.0% 23.6% 33.6
Multiple countries NR 1 669 1.9 3.9% 9.9% 0.7% NR NR 16.4
Totalc 4673 60 4,549,481 7.6 10.0% 14.6% 14.9% 29.1% 21.2% 32.2
CAD coronary artery disease, CVD cardiovascular disease (includes all complications), MI myocardial infarction, NR not reported
a
Adults aged 20–79. Source: IDF Atlas 2015 [1]
b
A study reports two separate analyses within the same paper; thus, there are 60 studies in 57 articles
c
Prevalence rates weighted by inverse variance
Page 8 of 19
Table 3 Number of studies and cardiovascular outcomes reported, by country

Country Income statusa Studies Patients Stroke MI Angina CHF Atherosclerosis CAD CVD (%)
Australia High 3b 1569 7.7% NR NR NR NR 21.8% 29.4

Belgium High 1 711 8.0% NR NR NR NR 22.0% 30.0
Brazil Upper middle 2 537 5.5% NR NR 4.2% NR 22.6% 27.5
Cameroon Low middle 1 132 5.0% NR NR NR NR 23.6% 28.6
China Upper middle 5 39,934 15.2% NR NR 4.3% 30.5% 17.0% 28.4
France High 1 987 15.3% NR NR 9.1% NR 29.5% 53.9
India Low middle 3b 1656 3.1% NR NR NR NR 29.4% 42.6
Indonesia Low middle 1 400 10.8% NR NR NR NR 28.8% 39.6
Iraq Upper middle 1 1079 NR NR NR NR NR NR 16.0
Ireland High 1 309 5.2% NR NR NR NR 17.8% 23.0
Italy High 5 19,869 2.4% 6.2% NR NR NR 11.1% 14.8
Korea High 2 654 20.3% NR NR NR 21.5% 37.0% 47.2
Mexico Upper middle 1 160 NR NR NR 57.5% NR NR 57.5
Netherlands High 3 899 6.1% NR NR 30.6% 33.0% 28.2% 44.5
Portugal High 1 3215 5.0% NR NR NR NR 12.0% 17.0
Qatar High 1 180 NR NR NR NR NR 31.7% 31.7
Russian Federation Upper middle 1 3,060,517 4.2% 3.4% NR NR NR 13.4% 21.0
Saudi Arabia High 2 2700 7.1% 11.4% NR NR NR 23.1% 30.0
Scotland High 3b 351,592 NR NR NR NR NR 19.7% 19.7
Spain High 7 430,855 8.0% 20.2% NR 30.3% NR 13.6% 29.8
Sweden High 3 453,791 10.3% 9.3% 14.6% 9.5% NR NR 31.3
Switzerland High 1 83 15.7% NR NR NR NR 33.7% 49.4
Thailand Upper middle 1 1505 2.5% NR NR NR NR NR 2.5
UK High 1 2733 7.9% NR NR NR NR 34.5% 42.4
USA High 7 170,803 10.9% 13.6% 17.2% 15.5% NR 28.1% 44.0
16 countries High 42 1,440,950 9.3% 12.1% 15.9% 19.0% 27.3% 24.3% 33.6
6 countries Upper middle 11 3,103,732 6.9% 3.4% 22.0% 30.5% 17.7% 25.5
3 countries Low middle 5 2188 6.3% 27.3% 36.9
0 countries Low 0 0
25 countries Overall 58 4,546,870c 8.4% 10.7% 15.9% 20.1% 28.3% 23.7% 32.1
CAD coronary artery disease (also reported as coronary heart disease or ischemic heart disease), CHF congestive heart failure, CVD cardiovascular disease, MI
myocardial infarction, NR not reported
a
World Bank status [117] based on Gross National Income per capita per annum (in USD) as of 01 July, 2016: Low < $1025; Low middle = $1026–$4035; Upper
middle = $4036–$12,475; High > $12,476. Country status extracted from World Bank Database [118]
b
A study reports two separate analyses within the same paper. In total there are 58 studies across 55 articles
c
Study evaluated patients from multiple countries and therefore is not included in this table. Thus, there are 4,546,870 patients across 55 studies
category of obesity. The highest category (BMI ≥ 40) had the articles were reporting of outcome data and report-
a prevalence rate of 5.01%, which was 27% lower than ing of outcomes. The two items addressed the least were
those in the lowest category (BMI < 20). Thus, patterns the statement of funding (56%) and indicating the study
vary quite widely, and studies often examined different design with a commonly used term in the title or abstract
outcomes. (60%).
Risk of bias in included studies Discussion

In the assessment of risk for bias, the studies addressed In this systematic review of 4,549,481 persons with
80% of the STROBE checklist items (i.e., research T2DM, we estimated the overall prevalence of CVD
design and data presentation), on average. The mean at 32.2%. The most frequent type of CVD reported was
was 80 ± 12%, and the median was 81%, with a range of CAD (21.2%) and lowest was stroke (7.6%). Males had
54–100%. The two items that were addressed by 100% of higher rates of prevalent disease than females. CVD was
Table 4 Summary of prevalence rates of cardiovascular comorbidities in persons with type 2 diabetes

Sex Cardiovascular outcome Studies N Ratea (%) 95%
confidence
interval (%)
Both Stroke 39 3,901,505 7.6 6.6–8.6

Myocardial infarction 13 3,518,833 10.0 7.5–12.5
Angina pectoris 4 354,743 14.6 12.0–17.3
Heart failure 14 601,154 14.9 13.0–16.7
Atherosclerosis 4 1153 29.1 21.7–36.4
Coronary artery disease 42 3,833,200 21.2 20.3–22.2
Cardiovascular disease (any) 53 4,289,140 32.2 30.0–34.4
Malesb Stroke 10 232,525 6.7 6.0–7.3
Myocardial infarction 2 1170 11.9 4.3–19.5
Angina pectoris 1 454 21.1 16.3–26.9
Heart failure 4 73,361 25.3 11.4–39.2
Coronary artery disease 9 237,367 18.7 16.5–20.8
Cardiovascular disease 16 241,406 27.6 25.3–29.9
Femalesb Stroke 10 202,348 5.9 5.1–6.7
Myocardial infarction 2 1812 9.8 3.5–16.0
Angina pectoris 1 803 17.4 15.0–20.2
Heart failure 4 62,690 24.0 11.2–36.8
Coronary artery disease 10 205,493 14.3 12.4–16.1
Cardiovascular disease 16 209,153 27.2 22.7–31.7
a
Weighted by inverse variance
b
No studies reported atherosclerosis for males or females; only in the aggregate. Rates for males and females do not sum to the total as not all studies reported all
outcomes
responsible for 50.3% of all deaths in T2DM patients 41, 43, 45, 46]. On the other hand, four studies reported
over the period of the review. Along with diabetes, car- no differences between age categories [26, 34, 48, 49].
diovascular disease is associated with several risk factors, Three other studies used age as a covariate in a logistic
obesity, and age. We, therefore, evaluated the association regression with no further details [28, 50, 51]. Therefore,
between age and obesity among patients with CVD and few studies have quantified the effect of age on CVD
T2DM in the selected articles. prevalence rates among people with T2DM.
Age as a risk factor for CVD Obesity as a risk factor for CVD

Age is a well-known risk factor for CVD. Out of the Obesity has long been established as an independent risk
57 articles, thirteen (25%) reported on the relation- factor for CVD [7, 52], and is associated with CAD [53,
ship between age and CVD and the results were quite 54], atherosclerosis [51], and cardiac death [55, 56]. Fur-
mixed. Nine studies identified a significant relation- thermore, it has been shown that overweight and obe-
ship between age and CVD [30, 38, 41–47], but only sity are highly prevalent in T2DM patients with high CV
two presented results across multiple age categories [38, risk and that BMI and waist circumference are related to
42]. Alonso-Moran [42] found that the odds ratio for major cardiometabolic risk factors such as hypertension
IHD, stroke, heart failure and MI all increased sequen- and elevated low-density lipoprotein cholesterol (LDL-C)
tially with each increase in 5-year age category as com- [57].
pared with the age group 35–39 used as a reference. All Obesity is usually defined by body mass index (BMI,
of these individual outcomes achieved statistical signifi- calculated as body weight in kg divided by the square of
cance (P < 0.001). Boonman-de Winter et al. [38] simi- height in meters), with the World Health Organization
larly reported a sequential increase in prevalence rates of (WHO) classifying adults with a BMI 30 kg/m2 as obese
heart failure for all patients in 5-year age categories from [58]. However, BMI as a measure to stratify patients
60 to 64 to > 80 years of age. Other authors reported that with obesity has limitations and does not account for
older patients had higher prevalence rates than younger the wide variation in body fat distribution nor the qual-
patients, but provided few details on age categories [30, ity of fat, and may not account for associated health risk
Table 5 Mortality associated with cardiovascular disease in persons with type 2 diabetes

Disease Author (year) Data collection Patients n All deaths % CVD Deaths % Death rate % CVD
period proportion
of all deaths
CVD Alwalkeel (2008) Jan 1989–Jan T2DM adults 1952 161 8.20% 97 5.00% 60.20%
[30] 2004
CVD Cardoso (2008) 1994–96 to 2001 T2DM adults 471 121 25.70% 44 9.30% 36.40%
[31]
CVD Carnethon (2010) 1989–93 to 2005 T2DM only 659 468 71.00% 211 32.0% 45.10%
[32]
CVD Carnethon (2010) 1989–93 to 2005 CVD only 868 620 71.40% 304 35.0% 49.00%
[32]
CVD Carnethon (2010) 1989–93 to 2005 T2DM + CVD 260 219 84.20% 129 49.60% 58.90%
[32]
CVD Carnethon (2010) 1989–93 to 2005 No T2DM or 3997 2095 52.40% 710 17.8% 33.90%
[32] CVD
CVD Eeg-Olofsson 1997–98 to 2003 T2DM adults 18,334 1902 10.40% 1456 7.90% 76.60%
(2010) [33]
CVD Malik (2015) [34] 2005–2011 T2DM adults 121,523 17,637 14.50% 3722 3.10% 21.10%
CVD Menzaghi (2014) 2001–2008 GHS study— 242 NR – 42 17.40% –
[36] males
CVD Menzaghi (2014) 2001–2008 GHS study— 117 NR – 16 13.70% –
[36] females
CVD Menzaghi (2014) 1993–1999 HPFS study— 833 NR – 146 17.50% –
[36] males
CVD Menzaghi (2014) 1976–1990 NMS study— 902 NR – 144 16.00% –
[36] females
CVD Salinero-Fort 2007–08 to 2012 T2DM adults 2442 203 8.30% 96 3.90% 47.30%
(2016) [35]
CVD Salinero-Fort 2007–08 to 2012 T2DM 965 221 22.90% 124 12.80% 56.10%
(2016) [35] adults + kid‑
ney disease
CVD Shestakova (2016) 2015 T2DM adults 3,060,516 66,093 2.20% 30,560 1.00% 46.20%
[29]
All CVD death Patients with 3,208,557 86,557 a 42.3%a 36,576a 9.9%a 50.3%a
T2DM
CAD Cardoso (2008) 1994–1996 to T2DM adults 471 121 25.70% 30 6.40% 24.80%
[31] 2001
CAD Carnethon (2010) 1989–1993 to T2DM only 659 468 71.00% 132 20.00% 28.20%
[32] 2005
CAD Carnethon (2010) 1989–1993 to CVD only 868 620 71.40% 213 24.50% 34.40%
[32] 2005
CAD Carnethon (2010) 1989–1993 to T2DM + CVD 260 219 84.20% 111 42.70% 50.70%
[32] 2005
CAD Carnethon (2010) 1989–1993 to No T2DM or 3997 2095 52.40% 425 10.60% 20.30%
[32] 2005 CVD
CAD Jackson (2012) 2001–2007 Male diabetics 116,145 22,033 19.00% 6000 5.20% 27.20%
[97]
CAD Jackson (2012) 2001–2007 Male non- 2,433,748 36,801 1.50%
[97] diabetics
CAD Jackson (2012) 2001–2007 Female diabet‑ 100,507 20,571 20.50% 4554 4.50% 22.10%
[97] ics
CAD Jackson (2012) 2001–2007 Female non- 2,630,482 32,449 1.20%
[97] diabetics
All CAD death Patients with 218,462a 42,944a 24.9%a 10,695a 6.3%a 29.7%a
T2DM
CHF Mazza (2007) 1983–1985 to Male diabetics 202 – – 22 10.90% –
[104] 1997
Table 5 (continued)
Disease Author (year) Data collection Patients n All deaths % CVD Deaths % Death rate % CVD
period proportion
of all deaths
CHF Mazza (2007) 1983–1985 to Female diabet‑ 379 – – 29 7.70% –

[104] 1997 ics
CHF Mazza (2007) 1983–1985 to All 581 369 63.50% – – 13.80%
[104] 1997
CHF Shestakova (2016) 2015 T2DM adults 3,060,516 66,093 2.20% 18,963 0.60% 28.70%
[29]
All CHF deaths Patients with 3,061,097a 66,093a 2.2%a 1,9104a 6.1%a 28.7%a
T2DM
MI Shestakova (2016) 2015 T2DM adults 3,060,516 66,093 2.20% 3393 0.10% 5.10%
[29]
SCD Kucharska-New‑ 1987–89 to 2001 T2DM adults 1550 NR – 69 4.50% –
ton (2010) [99]
SCD Kucharska-New‑ 1987–89 to 2001 No T2DM 12,428 NR – 140 1.10% –
ton (2010) [99]
Stroke Jackson (2012) 2001–2007 Male diabetics 116,145 22,033 19.00% 1942 1.70% 8.80%
[97]
Stroke Jackson (2012) 2001–2007 Male non- 2,433,748 13,191 0.50%
[97] diabetics
Stroke Jackson (2012) 2001–2007 Female diabet‑ 100,507 20,571 20.50% 2436 2.40% 11.80%
[97] ics
Stroke Jackson (2012) 2001–2007 Female non- 2,630,482 23,632 0.90%
[97] diabetics
Stroke Shestakova (2016) 2015 T2DM adults 3,060,516 66,093 2.20% 8204 0.30% 12.40%
[29]
All CBV deaths Patients with 327,168a 108,697a 3.30% 12,582a 1.50% 11.0%a
T2DM
CAD coronary artery disease (variously reported as coronary heart disease or ischemic heart disease), CBV cerebrovascular disease, CHF congestive heart failure (also
reported simply as heart failure), CVD cardiovascular disease, MI myocardial infarction, NR not reported, SCD sudden cardiac death, T2DM type 2 diabetes mellitus
a
Weighted average of rates taken only for patients with T2DM and where complete outcomes were reported; thus, the number does not represent the sum of all of
the numbers in the column above it
in different individuals and populations [58]. This has positive relationship between increasing BMI and CVD;
been shown to be true for South Asian populations [59]. except in one study [39], where women with severe
In a study from Raji et al. [60] noted that compared with obesity had a reduced prevalence of stroke. While the
Caucasians, Asian Indians had significantly greater total authors do not explain the reduced prevalence of stroke/
abdominal and visceral fat matched with Caucasians of TIA, it may be explained by differences in vascular risk
the same age, gender, and BMI, meaning that this pop- markers in men, such as pre-existing ischemic heart dis-
ulation has an increased CVD risk. Besides, there is a ease, age, and smoking [63]. Furthermore, the presence
weaker association between increasing BMI and T2DM of gonadal steroids, most notably estrogen, may lend a
in Asian populations compared with Caucasians due to protective effect against stroke/TIA in women and it has
the risk for T2DM begins increasing at comparatively been shown that adiposity is associated with increased
normal BMI in Asian populations [61]. levels of estrogen [64].
Seven of the included studies evaluated the relationship Although obesity is identified as a risk factor for CVD,
between obesity and/or BMI and CVD risk. Five of the it is associated with a paradox in that mortality is lower
studies included in this review identified a positive rela- in patients who are overweight or obese than in those
tionship between obesity and increased prevalence rates whose BMI is normal or underweight [65]. Lee et al.
of CVD [26, 37–40]. One of these studies [26] used lower [66] reported that obesity provided a survival benefit to
BMI cut-off points to account for Asian populations in patients with heart failure who did not have comorbid
accordance with WHO recommendations on BMI for diabetes, but not in patients who did have concomitant
Asian populations [62] and evaluated abdominal adipos- diabetes. In contrast, a group led by Abi Khalil [67] exam-
ity with waist circumference measurements to determine ined a cohort of 2492 T2DM patients in seven countries
the prevalence of obesity. Overall, the studies found a in the Middle East, Gulf region, with acute heart failure.
They reported that BMI was inversely correlated with the countries and clearly shows that few studies exist for sev-
risk of mortality, with severe obesity associated with less eral regions. For example, only one study from one coun-
mortality risk. try in the African region was identified and therefore
It is clear that the relationship between obesity and should not be seen to represent findings for the region’s
the risk of CVD and CVD-related deaths requires fur- entire T2DM population.
ther exploration to identify these mechanisms and Treatment of both T2DM and CVD vary greatly
relationships. between and within countries, and although much of
the CVD risk in T2DM can be associated with the long-
CVD‑related mortality in T2DM
term complications of T2DM, there has been growing
In persons with T2DM, CVD is responsible for at least interest to determine whether certain antidiabetic drugs
half of the mortality, as previously mentioned. Among the influence this risk. For example, sulfonylureas which are
specific diseases within that term, CAD was most lethal, the second most commonly used antidiabetic drug after
followed by stroke. Similar results have been demon- metformin, have been shown to be associated with an
strated with other models. In an incidence-based study, increased risk of cardiovascular events and mortality
Straka et al. [68] followed 29,863 patients (5501 with [71]. Newer antidiabetic drugs have been shown to lower
T2DM and 24,362 without T2DM) over a 1-year period. the risk of CVD in T2DM patients [17–20]; however,
Four of the incident cardiovascular outcomes they these drugs are often intended to be used as second- to
reported were significantly higher in those with T2DM. third-line treatments and many years may pass before
Patients with T2DM had 10% greater risk of CAD, 53% of patients can benefit.
MI, 58% of stroke, and 112% increased risk of heart fail-
Temporal trends in CVD risk assessment and management
ure. Therefore, T2DM is a substantial risk factor for CVD
in T2DM
and its consequences.
Encouragingly, CVD mortality is declining in high-
income countries among the general population due
to reductions in cardiovascular risk factors as well as to
CVD prevalence rates across regions and countries
recent advances in prevention, treatment, and manage-
As this was a global review, studies from across the world
ment [72]. This trend has also been observed in people
were included. Given the variation in which diabetes and
with T2DM in some countries. Jung et al. [73] estimated
its macrovascular complications are treated and managed
trends in CVD in people with and without T2DM in
across countries and income levels, it is relevant to look
South Korea using data from the national health insur-
at prevalence rates across regions and countries. How-
ance system. The results show a significant reduction
ever, almost half (46.0%) of the research was produced
in CVD risk among people with T2DM brought on by
in Europe, and very little information was obtained from
improvements in the care and management of patients.
the less developed regions of the world such as Africa,
However, in many developing countries where the bur-
Latin America, and the Asian subcontinent.
den of T2DM is rapidly rising and lifestyle patterns
As shown in Table 2, the regions with the highest
changing an increase in CV risk factors among people
prevalence of overall CVD were North America and Car-
with T2DM can be expected [3]. A study from China
ibbean (46.0%; N = 4,327,503), Southeast Asia (42.5%,
analyzed the relationship between lifestyle behaviors and
N = 537) and Western Pacific (including China) (33.6%;
multiple CV risk factors in 25,454 people with T2DM
N = 44,062). Southeast Asia stands out with a higher
[74]. The researchers found that unhealthy lifestyles were
prevalence of CAD (29.4%) compared with other regions.
common, especially among those who are non-elderly,
The prevalence of CAD in this region is driven by one
and above-college educated. Furthermore, it was found
study from India [69], which specifically investigated
that an unhealthy lifestyle was associated with poor
the pattern of CAD in 134 symptomatic T2DM patients
blood, blood lipid, and blood pressure control. Decreas-
in India. However, epidemiological studies on people of
ing the impact of T2DM and CVD in developing coun-
South Asian origin have shown an increased likelihood
tries will require interventions aimed at changing risky
of developing CAD that is up to two times higher than
lifestyle behaviors.
in Caucasians [70]. The higher risk is due to both patho-
Screening people with T2DM for CV risk is an impor-
physiological and life course-related risk factors [70].
tant strategy for reducing mortality and CVD events. A
The summaries across countries and regions provide an
study from Denmark [75] found that a single round of
overview of the geographic spread of research but should
diabetes screening and cardiovascular risk assessment
be interpreted with caution given the limited number of
in middle-aged adults in general practice was associ-
studies for some of the regions and countries. Figure 2
ated with a significant reduction in risk of all-cause
illustrates the distribution of studies across regions and
Fig. 2 Distribution of studies across countries and regions. The figure illustrates the global distribution of studies across countries and regions
mortality and CVD events in people with T2DM. The In addition, coronary artery calcium (CAC) assessments
same researchers found that population-based stepwise have been found to significantly improve the risk clas-
screening for T2DM and CVD among all middle-aged sification for CHD and atherosclerotic CVD events in
adults was not associated with a reduction in mortality people with T2DM—regardless of the duration of diabe-
or CV events. Therefore, the benefits of population-based tes [80]. Thus, a CAC assessment can be a useful tool for
screening are limited in this context [76]. Kesall et al. [77] classifying people with T2DM into lower- or higher-risk
found that targeting specific occupational and industry groups for long-term CVD risk.
groups with health checks could help identify individu- Lipid profile has long been considered among the most
als at high risk of both T2DM and CVD. In a study of important risk factors for CVD in T2DM, and several tri-
500,000 members of the Australian working population, als have confirmed that lowering low-density lipoprotein
they found that high T2DM and CVD risk was increased cholesterol (LDL-C) via statins in T2DM was effective in
significantly in many occupational groups and industries. reducing the risk of CVD [81, 82]. It is also well known
Recent research points to an increasingly better under- that statins also have a triglyceride-lowering effect [83]. In
standing of the markers for identifying high CVD risk in a cross-sectional study of 223,612 patients with T2DM in
people with T2DM. Li et al. [78] found that the combined China, researchers found that although lower triglyceride
application of carotid and lower extremity ultrasonogra- was associated with reduced CVD risk in the short-term,
phy may be helpful to identify patients with T2DM who it was associated with increased risk in the long-term
have a higher CVD risk. In a study of 2830 hospitalized [84]. This paradox could mean that low triglyceride is
patients with T2DM, they found that the concomitant not necessarily associated with good clinical outcomes
presence of carotid and lower extremity atherosclerosis in all people with T2DM and that there are subgroup
further increases the risk of CVD in patients with T2DM, associations with CVD in patients with different dura-
compared with those who had either carotid or lower tions of T2DM. Furthermore, Clua-Espuny et al. [85]
limb atherosclerosis and those without atherosclerosis. A suggest that the relative importance of risk factors wanes
study by Mohammedi et al. [79] found that major periph- in complex chronic patients with T2DM with advancing
eral arterial disease (PAD) presenting as lower-extremity age. In a cohort study of almost 3500 complex chronic
ulceration or amputation and peripheral revasculariza- patients above the age of 80 of whom 53% had diabetes
tion is associated with increased risk of death and CV and a high prevalence of associated classical risk factors,
events in people with T2DM. The researchers conclude the researchers found that all-cause mortality was more
that screening for PAD along with active management affected by aging factors than by specific complications of
are crucial for prevention of CVD in people with T2DM. diabetes. The authors make the recommendation that, for
these patients, the care strategy may need to be redefined thus lead to an overestimate of the prevalence of CVD.
and adapted to comorbidities and functional autonomy Second, some of the studies included T2DM patients
rather than being focused on treatment outcomes. with an existing CVD diagnosis; therefore, the overall
estimate of CVD within these studies could be higher
Limitations compared to the broader T2DM population.
As with all literature reviews, we were limited by the Finally, only 25 countries were represented in this
availability of the literature and the validity and quality of analysis. Noticeably absent were such countries as Ger-
the articles. Some of the results appeared only in abstract many, Canada, and Denmark, which all have excellent
form, and many were not subsequently published as full electronic health data, yet no research studies have
articles within the time horizon of this review. Abstracts been published from them. Very little has appeared
had space limitations, restricting the amount of informa- from Africa, the Asian subcontinent or Latin Amer-
tion they could present. As well, we noted that there was ica. More studies from these areas would be welcome.
often incomplete reporting or selective reporting of spe- While the scope of this study was to evaluate evidence
cific outcomes of interest. from peer-reviewed literature, an alternative approach
Furthermore, the findings of this literature review to estimating the prevalence of CVD among patients
are limited to a select patient population. Specifically, with T2DM could be to analyze data within existing
in this research, we accepted only data from adults registries.
aged 18 or older. Therefore, our results may not apply
to children or adolescents. As well, we dealt only with Conclusions
T2DM; therefore, outcomes may not apply to T1DM or This is the first systematic review to synthesize global
secondary diabetes such as that associated with hemo- prevalence rates of CVD, including stroke, MI, angina,
chromatosis or pancreatitis. heart failure, atherosclerosis and CAD among peo-
This study was also challenged by the fact that CVD ple with T2DM. The results show that CVD is a major
and its associated conditions are described differ- cause of comorbidity and death among patients with
ently across the literature. For example, CHD was T2DM with CAD having the highest prevalence. There
used interchangeably with CAD or ischemic heart dis- is a paucity of research studies investigating both the
ease. We made every effort to standardize definitions prevalence of CVD and risk factors such as obesity
and to group like with like. Furthermore, the types of among people with T2DM. Given the large burden that
CVD conditions evaluated varied across articles. Some CVD exerts on healthcare systems, patients and fami-
articles focused on a single outcome, whereas others lies around the world, more evidence is needed, ide-
focused on several outcomes. As a result, the calculated ally in the form of registry studies, to more accurately
prevalence rates may represent underestimates, as not quantify the global prevalence of CVD among people
all studies reported all outcomes. with T2DM.
The types of studies included would have also Authors’ contributions
impacted the overall results of this study. First, we ana- TRE, AA, CL and UHP made substantial contributions to conception and
design, or acquisition of data, or analysis and interpretation of data; been
lyzed only prevalence studies; incidence studies would involved in drafting the manuscript or revising it critically for important intel‑
have different results due to their different perspec- lectual content. All authors read and approved the final manuscript.
tive. Second, the studies varied both in the method of
Author details
data collection (e.g., national databases versus clinic 1
Leslie Dan Faculty of Pharmacy, University of Toronto, Barrie, Canada. 2 Last
records) and the length of time over which they col- Mile, Holte, Denmark. 3 Novo Nordisk A/S, Søborg, Denmark.
lected data. It is plausible that time-period over which
Acknowledgements
studies were conducted could have impacted the This research was funded by Novo Nordisk A/S, Bagsværd, Denmark.
observed prevalence rate of CVD. For example, health TRE, AA, and CL all received consulting fees for undertaking this project.
status, lifestyle, and treatments have varied over time,
which could impact the prevalence rates in the studies Competing interests
using older data. TRE, AA, and CL all received consulting fees for undertaking this project. UHP
Overall, it is possible that the prevalence estimates is an employee of Novo Nordisk A/S.
for CVD presented in this article overestimate the Availability of data and materials
prevalence of CVD among patients with T2DM. First, Data sharing is not applicable to this article as no datasets were generated or
studies in the medical literature tend to include a sicker analyzed during the current study.
population compared to the general T2DM population; Consent for publication
therefore, due to self-selection bias, the sample may not Not applicable.
be representative of the broader T2DM population and
Ethics approval and consent to participate 17. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay
Not applicable. I, Rosenstock J, Seufert J, Warren ML. Semaglutide and cardiovas‑
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Funding 2016;375:1834–44.
This research was funded by Novo Nordisk A/S, Bagsværd, Denmark. 18. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck
MA, Nissen SE, Pocock S, Poulter NR, Ravn LS. Liraglutide and cardiovas‑
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Publisher’s Note 19. Sanon VP, Patel S, Sanon S, Rodriguez R, Pham SV, Chilton R. Differential
Springer Nature remains neutral with regard to jurisdictional claims in pub‑ cardiovascular profiles of sodium-glucose cotransporter 2 inhibitors:
lished maps and institutional affiliations. critical evaluation of empagliflozin. Ther Clin Risk Manag. 2017;13:603.
20. Trujillo JM, Nuffer WA. Impact of sodium–glucose cotransporter 2
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Einarson 2018

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et al. Cardiovasc Diabetol (2018) 17:83

REVIEW Open Access

Prevalence of cardiovascular disease

Background macrovascular complications appears to be multifacto-

Records idenfied through Addional records idenfied

Records aer duplicates removed

Records screened Records excluded

Full-text arcles assessed Full-text arcles excluded, with

Table 1 Overview of studies in the analysis

BMI body mass index, NR not reported, SD standard deviation

Africa 441 1 132 5.0 NR NR NR NR 23.6% 28.6

Table 3 Number of studies and cardiovascular outcomes reported, by country

Australia High 3b 1569 7.7% NR NR NR NR 21.8% 29.4

Risk of bias in included studies Discussion

Table 4 Summary of prevalence rates of cardiovascular comorbidities in persons with type 2 diabetes

Both Stroke 39 3,901,505 7.6 6.6–8.6

Age as a risk factor for CVD Obesity as a risk factor for CVD

Table 5 Mortality associated with cardiovascular disease in persons with type 2 diabetes

CHF Mazza (2007) 1983–1985 to Female diabet‑ 379 – – 29 7.70% –

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Records idenfied through Addional records idenfied

Records aer duplicates removed

Full-text arcles assessed Full-text arcles excluded, with

Table 1 Overview of studies in the analysis

Table 3 Number of studies and cardiovascular outcomes reported, by country

Table 4 Summary of prevalence rates of cardiovascular comorbidities in persons with type 2 diabetes

Table 5 Mortality associated with cardiovascular disease in persons with type 2 diabetes