359
ORIGINAL SCIENTIFIC ARTICLE
Cardiovascular complications in hyperthyroid patients with Graves’ disease or subacute thyroiditis
Copyright (c) 2024 Slovenian Medical Journal. This work is licensed under a
Creative Commons Attribution-NonCommercial 4.0 International License.
A higher incidence of cardiovascular complications in 
hyperthyroid patients with Graves’ disease in comparison 
to hyperthyroid patients with subacute thyroiditis
Pogostejše pojavljanje srčno-žilnih zapletov pri bolnikih s hipertirozo zaradi 
bazedovke kot pri bolnikih s hipertirozo zaradi subakutnega tiroiditisa
Ana Šešek,1 Simona Gaberšček,1,2 Katja Zaletel,1,2 Edvard Pirnat,1,2 Katica Bajuk Studen1,2
Abstract
Background: Hyperthyroidism, as well as systemic inflammation, are associated with a higher incidence and complica-
tions of cardiovascular disease. Both in Graves’ disease and subacute thyroiditis, patients are hyperthyroid. However, in 
Graves’ disease, there is an autoimmune process in the thyroid, and in subacute thyroiditis, hyperthyroidism is accompa-
nied by systemic inflammation. It is not known if the rate of cardiovascular complications is higher in the course of Graves’ 
disease or subacute thyroiditis.
Methods: We performed a retrospective study of all hyperthyroid patients newly diagnosed with Graves’ disease or sub-
acute thyroiditis between January 1st 2018 and December 31st 2021 at the Department of Nuclear Medicine, University 
Medical Centre Ljubljana. Cardiovascular complications in the period 3 months before or after diagnosis were registered. 
Values are expressed as mean (SD).
Results: The sample analysis included 1028 patients (247 with subacute thyroiditis, 781 with Graves’ disease). The two 
groups did not significantly differ by sex, age, and body mass index. A cardiovascular complication was registered in 78 pa-
tients; the incidence was significantly higher in Graves’ disease than in subacute thyroiditis (74 vs. 4, p<0.001). Compared 
to patients with subacute thyroiditis, patients with Graves’ disease had significantly lower TSH: 0.010 (0.006) vs. 0.024 
(0.044) mIU/L (p<0.001), higher free T4: 44.1 (26.6) vs. 37.0 (14.7) pmol/L (p<0.001), higher incidence of diabetes: 4.3 vs. 
0.4% (p=0.001), arterial hypertension: 12.2 vs. 5.7% (p=0.004) and smoking: 26.7 vs. 8.7% (p<0.001). In a logistic regression 
model, a significantly higher likelihood for cardiovascular complications was found in Graves’ disease vs. subacute thy-
roiditis (odds ratio 5.82, p=0.001), in patients with arterial hypertension (odds ratio 2.83, p=0.002), and in those with higher 
body mass index (odds ratio 0.92, p=0.043).
1 Medicinska fakulteta, Univerza v Ljubljani, Ljubljana, Slovenija
2 Klinika za nuklearno medicino, Univerzitetni klinični center Ljubljana, Ljubljana, Slovenija
Correspondence / Korespondenca: Katica Bajuk Studen, e: katica.bajuk@gmail.com
Key words: hyperthyroidism; thyroiditis; cardiovascular events; inflammation
Ključne besede: hipertiroza; tiroiditis; srčno-žilni zapleti; vnetje
Received / Prispelo: 19. 10. 2023 | Accepted / Sprejeto: 5. 9. 2024
Cite as / Citirajte kot: Šešek A, Gaberšček S, Zaletel K, Pirnat E, Bajuk Studen K. A higher incidence of cardiovascular complications in 
hyperthyroid patients with Graves’ disease in comparison to hyperthyroid patients with subacute thyroiditis. Zdrav Vestn. 2024;93(11–
12):359–66. DOI: https://doi.org/10.6016/ZdravVestn.3508
eng slo element
en article-lang
10.6016/ZdravVestn.3508 doi
19.10.2023 date-received
5.9.2024 date-accepted
Cardiovascular system Srce in obtočila discipline
Original scientific article Izvirni znanstveni članek article-type
A higher incidence of cardiovascular complica-
tions in hyperthyroid patients with Graves’ dis-
ease in comparison to hyperthyroid patients 
with subacute thyroiditis
Pogostejše pojavljanje srčno-žilnih zapletov pri 
bolnikih s hipertirozo zaradi bazedovke kot pri 
bolnikih s hipertirozo zaradi subakutnega tiroid-
itisa
article-title
Cardiovascular complications in hyperthyroid 
patients with Graves’ disease or subacute 
thyroiditis
Pogostejše pojavljanje srčno-žilnih zapletov pri 
bolnikih s hipertirozo zaradi bazedovke kot pri 
bolnikih s hipertirozo zaradi subakutnega tiroid-
itisa
alt-title
hyperthyroidism, thyroiditis, cardiovascular 
events, inflammation hipertiroza, tiroiditis, srčno-žilni zapleti, vnetje kwd-group
year volume first month last month first page last page
2024 93 11 12 359 366
name surname aff email
Katica Bajuk Studen 1,2 katica.bajuk@gmail.com
name surname aff
Ana Šešek 1
Simona Gaberšček 1,2
Katja Zaletel 1,2
Edvard Pirnat 1,2
eng slo aff-id
Faculty of Medicine, University 
of Ljubljana, Ljubljana, Slovenia
Medicinska fakulteta, Univerza v 
Ljubljani, Ljubljana, Slovenija 1
Department of Nuclear 
Medicine, University Medical 
Centre Ljubljana, Ljubljana, 
Slovenia
Klinika za nuklearno medicino, 
Univerzitetni klinični center 
Ljubljana, Ljubljana, Slovenija
2
Slovenian Medical Journallovenian Medical Journal
360
CARDIOVASCULAR SYSTEM
Zdrav Vestn | November – December 2024 | Volume 93 | https://doi.org/10.6016/ZdravVestn.3508
1 Introduction
Graves’ disease (GD) is the most common autoim-
mune thyroid disease causing hyperthyroidism, with an 
incidence of 30–35/100,000 in Slovenia (1). Subacute 
thyroiditis (ST), or viral, de Ouervain’s subacute gran-
ulomatous thyroiditis is a self-limiting inflammatory 
disease of the thyroid gland that sometimes follows a 
viral infection. Its clinical course is usually accompa-
nied by transient hyperthyroidism. It has an incidence 
of 9–10/100,000 (1,2).
Thyroid hormones thyroxine (T4) and triiodo-
thyronine (T3) affect cardiac function, especially the 
contractility, frequency, and compliance of the heart 
wall, as well as peripheral blood vessels, by influenc-
ing endothelial cells and smooth muscle (3-5). Hyper-
thyroidism has been associated with cardiac arrhyth-
mias, heart failure, acute myocardial infarction (AMI), 
stroke, and hypercoagulopathy. A large epidemiolog-
ical study reported increased all-cause mortality and 
serious adverse cardiovascular (CV) complications in 
overt and subclinical hyperthyroidism compared with 
Conclusion: We report a higher incidence of cardiovascular complications in hyperthyroid patients with Graves’ disease 
in comparison to hyperthyroid patients with subacute thyroiditis. Patients with Graves’ disease were more severely hyper-
thyroid and had more adverse cardiovascular risk factors.
Izvleček
Izhodišče: Povezava med hipertirozo in večjim tveganjem za pojav in zaplete srčno-žilnih bolezni je znana, prav tako pa 
tudi povezava med okužbami oz. vnetjem in srčno-žilnimi dogodki. Pri subakutnem tiroiditisu se v klinični sliki prepletata 
tako hipertiroza kot sistemsko vnetje, pri bazedovki pa gre za avtoimunski vnetni proces, ki je omejen na ščitnico. Zaenkrat 
ni znano, ali se srčno-žilni dogodki pogosteje pojavljajo pri bolnikih s hipertirozo zaradi bazedovke ali zaradi subakutnega 
tiroiditisa.
Metode: V retrospektivni raziskavi smo zbrali podatke vseh bolnikov s hipertirozo in bazedovko ali subakutnim tiroiditi-
som, ki so bili na Kliniki za nuklearno medicino UKC Ljubljana prvič obravnavani v obdobju med januarjem 2018 in de-
cembrom 2021, in so v obdobju 3 mesecev pred postavitvijo diagnoze ali po njej doživeli srčno-žilni dogodek. Vrednosti so 
izražene kot povprečje (SD).
Rezultati: V analizo je bilo vključenih 1.028 bolnikov (247 s subakutnim tiroiditisom, 781 z bazedovko). Skupini se po spo-
lu, starosti in indeksu telesne mase nista statistično pomembno razlikovali. Srčno-žilni dogodek je doživelo 78 bolnikov, 
od tega statistično značilno več v skupini z bazedovko (4 s subakutnim tiroiditisom, 74 z bazedovko, p<0,001). Bolniki z 
bazedovko so imeli v primerjavi z bolniki s subakutnim tiroiditisom značilno nižji TSH: 0,010 (0,006) proti 0,024 (0,044) 
mIU/L (p<0,001), višji prosti T4: 44,1 (26,6) proti 37,0 (14,7) pmol/L (p<0,001), večjo pojavnost sladkorne bolezni: 4,3 % 
proti 0,4 % (p=0,001), arterijske hipertenzije: 12,2 % proti 5,7 % (p=0,004) in kajenja: 26,7 % proti 8,7 % (p<0,001). Model 
logistične regresije je pokazal, da je tveganje za pojav srčno-žilnega dogodka značilno večje v skupini z bazedovko kot v 
skupini s subakutnim tiroiditisom (razmerje obetov 5,82, p=0,001), pri bolnikih z arterijsko hipertenzijo (razmerje obetov 
2,83, p=0,002) in višjim indeksom telesne mase (razmerje obetov 0,92, p=0,043).
Zaključek: Srčno-žilni dogodki se pojavljajo statistično značilno pogosteje pri bolnikih s hipertirozo in bazedovko kot pri 
bolnikih s hipertirozo in subakutnim tiroiditisom. Bolniki z bazedovko so bolj hipertirotični in imajo več neugodnih dejav-
nikov tveganja za razvoj srčno-žilnih bolezni.
euthyroidism (6). A meta-analysis of 37 cohort stud-
ies reported increased CV morbidity and mortality in 
hyperthyroid patients (7). A large case-control study 
reported an increased risk of CV disease in untreated 
hyperthyroid patients, and the duration of decreased 
thyroid stimulating hormone (TSH) was associated 
with an increased risk of adverse CV outcomes in both 
treated and untreated hyperthyroid patients (8). Overt 
and subclinical hyperthyroidism has been associated 
with increased markers of thrombogenesis (fibrinogen 
and factor X levels) and higher von Willebrand anti-
gen levels, leading to increased platelet plug formation, 
which decreased after treatment (9-12). A limited body 
of evidence also suggests an association between hy-
perthyroidism and increased risk of venous and arte-
rial thrombosis (12,13). Whether the increased risk of 
stroke in hyperthyroid patients is accounted for by the 
increased prevalence of atrial fibrillation (AF) in this 
population or by hyperthyroidism itself is still debated 
(12).
361
ORIGINAL SCIENTIFIC ARTICLE
Cardiovascular complications in hyperthyroid patients with Graves’ disease or subacute thyroiditis
Systemic inflammation, as encountered in ST (but 
not in GD, where the autoimmune inflammation pro-
cess is limited to the thyroid gland and potentially to 
the eyes and skin), can act as a systemic stressor, lead-
ing to an excessive inflammatory response and causing 
harmful, systemic spread of inflammatory mediators, 
which can gradually lead to the worsening and progres-
sion of other diseases (14). Inflammation is one of the 
key triggers of non-infectious heart disease, which oc-
curs in long-term systemic and vascular diseases (15). 
There is a clearly proven connection between influenza 
or sudden respiratory infections and a six-fold higher 
frequency of AMI during the narrow time period of 
recovery from these infections (16). The processes con-
tributing to acute coronary syndrome (ACS) develop-
ment in infection are acute inflammation, biomechan-
ical stress, and vasoconstriction (16). The metabolism 
is, therefore, further accelerated, which can lead to a 
reduced concentration of oxygen in the arterial blood 
and reduced blood pressure (16). This can lead to the 
development of occlusion of the vessel with a clot and 
the resulting ACS (16).
Since there is a clear association between hyper-
thyroidism and complications of CV disease and also 
between systemic inflammation and complications of 
CV disease, this study was designed to compare the in-
cidence of CV complications in hyperthyroid patients 
with GD (autoimmune thyroid disease) and in hyper-
thyroid patients with ST where systemic inflammation 
is present.
2 Methods
In a retrospective study, medical records of all hy-
perthyroid patients newly diagnosed with GD or ST at 
the Department of Nuclear Medicine, University Med-
ical Centre Ljubljana, between January 1st 2018 and 
December 31st 2021, were examined. The study was 
approved by the Republic of Slovenia National Medical 
Ethics Committee (No. 0120-515/2018/7).
The following data were collected:
• patient’s age, gender, date of diagnosis, date of po-
tential CV complication;
• risk factors for CV disease: arterial hypertension, 
smoking, hyperlipidemia, diabetes, body mass in-
dex (BMI);
• laboratory values: TSH, free T4, free T3, sedimen-
tation rate in ST patients, thyroid peroxidase anti-
bodies (TPOAb), thyroglobulin antibodies (TgAb), 
TSH-receptor antibodies (TSH-R Ab).
Arterial hypertension was defined as systolic blood 
pressure higher than 140 mmHg or diastolic blood 
pressure higher than 90 mmHg, previous diagnosis I10 
in the International Classification of Diseases 10 (ICD-
10), or if taking antihypertensive medication. The vari-
able smoking was defined as regular smoking at the 
time of diagnosis, whereas ex-smokers and occasional 
smokers were analysed as non-smokers. Hyperlipid-
emia was marked as present if the serum low density 
lipoprotein value was above 2.59 mmol/L, previous 
ICD-10 diagnosis E78, or if taking antihyperlipidemic 
medication. Diabetes mellitus was defined as a previ-
ous ICD-10 diagnosis of E10, E11, or O24 or taking 
anti-glycaemic medication. BMI was calculated based 
on collected weight and height data using the standard 
formula: dividing weight (kg) by square height (m2) 
(2). Furthermore, BMI was noted as increased if it ex-
ceeded 25.0 kg/m2.
GD and ST were diagnosed by an experienced thy-
roid specialist. GD was diagnosed based on the follow-
ing: clinical symptoms and signs of hyperthyroidism; 
laboratory findings: decreased serum level of TSH, el-
evated serum level of free T4 and/or free T3, elevated 
TSH-R Ab; thyroid ultrasound: hypoechoic and het-
erogeneous thyroid structure with increased paren-
chymal vascularity; in selected cases, increased uptake 
on thyroid scan with technetium-99m pertechnetate. 
ST was diagnosed based on the following: swelling 
with pain and tenderness of the thyroid gland; labo-
ratory findings: elevated sedimentation rate (SR), de-
creased serum level of TSH, elevated serum level of 
free T4 and/or free T3; thyroid ultrasound: hypoecho-
ic lesions in the painful region of the thyroid gland; 
and, in selected cases, suppressed thyroid scintigraphy 
with technetium-99m pertechnetate (2). Only overtly 
hyperthyroid patients (TSH below and free T4/free T3 
level above normal value) were included in the final 
analysis. A CV complication was registered according 
to data in the patient’s paper and electronic documen-
tation if, in the period 3 months before or 3 months 
after the diagnosis of ST or GD, the patient suffered 
one of the following: sudden cardiac death, AMI (both 
non-ST-elevation myocardial infarction or ST-eleva-
tion myocardial infarction), unstable angina pectoris, 
AF, tachycardia (except sinus tachycardia and AF), 
atrioventricular block, transient ischemic attack (TIA), 
stroke, deep vein thrombosis or pulmonary embolism. 
AMI, sudden cardiac death or stroke were considered 
major adverse CV events.
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2.1 Laboratory measurements
All laboratory measurements were performed at the 
biochemical laboratory of the Department of Nuclear 
Medicine at the University Medical Centre Ljubljana. 
Serum concentrations of TSH, free T4, and free T3 were 
measured using a chemiluminescence immunoassay 
(Advia Centaur till January 2021, afterward Atellica, 
both Siemens Healthineers). Ranges of TSH 0.59–4.23 
mIU/L, free T4 11.5–22.7 pmol/L, and free  T3  3.5–
6.5 pmol/L were considered normal. SR was measured 
semi-automatically (Sediko m10, Laboratorijska tehni-
ka Burnik, Slovenia).
2.2 Statistical analysis
Data is expressed as mean (SD). A two-way t-test 
for independent samples was used for normally dis-
tributed variables, and the Mann-Whitney u-test 
for variables that were not normally distributed. The 
analysis of descriptive variables was performed with 
Pearson’s χ2-test or Fisher’s exact test, the choice of 
test depending on the value of the expected frequen-
cies. Multivariate logistic regression was performed to 
assess the relative contribution of variables to cardio-
vascular complications; p-value <0.05 was considered 
statistically significant.
Statistical processing was performed with the GNU 
PSPP version 1.2.0-g0fb4db, Free Software Founda-
tion) (PSPP). Pivot tables of the Excel program and 
the online tool Easy Fisher Exact Test Calculator (Web 
tool 1, Social Science Statistics, version 2022) were al-
so used. Fisher Exact Probability Test: 2x4 was calcu-
lated by Web Tool 2, Vassarstats.net, Richard Lowry 
2001-2022).
3 Results
The final analysis included 1028 hyperthyroid pa-
tients (247 with ST and 781 with GD) (Figure 1).
Baseline demographic data, risk factors for CV dis-
ease, and TSH and thyroid hormone values at the diag-
nosis are outlined in Table 1. The mean value of the SR 
in the ST group was 64 (27) mm/h.
The CV complications registered in the ST and the 
GD groups are depicted in Figure 2, respectively. The 
incidence of CV complications in the GD group was sig-
nificantly higher than in the ST group (p<0.001).
As evident from Figure 2, CV complications were re-
corded in 78 (7.6%) patients. In the ST group, 4 (1.6%) 
had a CV complication, their average age was 44.8 (19.1) 
years, and 3 (75%) were women. In the GD group, 74 
(9.5%) patients suffered a CV complication, their average 
age was 53.2 (17.6) years, and 43 (58.1%) were women. 
The groups of patients with GD and ST who suffered a 
CV complication did not differ statistically significantly 
by age (p=0.87) or gender (p=0.64). The patient’s average 
age at the time of thyroid disease with the CV complica-
tion was 52.8 (17.7) years which was statistically signifi-
cantly higher than the average age in patients without a 
CV complication: 45.9 (14.0) years, p=0.002.
In both groups, 37 patients (47.4% of CV compli-
cations) had AF (absolute values and proportions are 
shown in Figure 2). The ST and GD groups did not differ 
significantly in the incidence of AF (p=0.62). The ST and 
GD groups did not differ significantly in the occurrence 
of two out of three major adverse CV events (AMI and 
stroke while no sudden cardiac death was recorded): 
one event (AMI) occurred in the ST group and 17 in the 
GD group (14 patients suffered AMI, 3 patients stroke) 
(p>0.99).
Figure 1: Flowchart for the study sample. One patient fulfilled the diagnostic criteria for subacute thyroiditis and Graves’ 
disease simultaneously and was not included in further analysis.
19 491 
patients screened in the 
period 1/1/2018 and 
31/12/2021
1 454
patients diagnosed with 
subacute thyroiditis 
and/or Graves’ disease
341
patients with subacute 
thyroiditis
1 112
patients with Graves’ 
disease
247 
hyperthyroid patients 
with subacute 
thyroiditis
781
hyperthyroid patients 
with Graves’ disease
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ORIGINAL SCIENTIFIC ARTICLE
Cardiovascular complications in hyperthyroid patients with Graves’ disease or subacute thyroiditis
Legend: ST – subacute thyroiditis; GD – Graves’ disease.
* In the ST group, type 2 diabetes was diagnosed in 1 patient. In the GD group, type 1 diabetes was diagnosed in 5 patients, type 
2 diabetes in 22 patients and gestational diabetes in 7 patients.
Parameter Subacute thyroiditis
(N=247)
Graves’ disease
(N=781)
p-value
Gender (female/male; % female) 182/65 (73.7%) 604/177 (77.3 %) 0.24
Age (years) 46.8 (11.9) 46.2 (15.2) 0.61
Body mass index (kg/m2) 24.2 (3.8) 24.2 (5.9) 1.0
Hyperlipidemia (%) 5 (2.0%) 33 (4.2%) 0.12
Diabetes* (%) 1 (0.4%) 34 (4.3%) 0.001
Arterial hypertension (%) 14 (5.7%) 95 (12.2%) 0.004
Smoking (%) 19 (8.7%) 188 (26.7%) <0.001
TSH (mIU/L) 0.024 (0.044) 0.010 (0.006) <0.001
Free T4 (pmol/L) 37.0 (14.7) 44.1 (26.6) <0.001
Free T3 (pmol/L) 16.85 (69.57) 19.50 (11.33) 0.32
Table 1: Clinical characteristics of patients with hyperthyroidism due to subacute thyroiditis or Graves’ disease. Data is 
reported as mean (SD) or number of cases (% of whole sample).
Figure 2: Cardiovascular complications in patients with subacute thyroiditis (N=4) and in patients with Graves’ disease (N=74).
0
3
5
7
8
10
Acute Ischemia of a Limb
14
15
Number of patients
Ca
rd
io
va
sc
ul
ar
 c
om
pl
ic
at
io
n
20 25 30 35 40
0
0
0
0
0
1
1
1
1
1
1
1
3
36
Acute Myocardial Infarction
Atrial Fibrilation
Atrioventricular Block
Deep Vein Thrombosis
Stroke
Tahycardias (except Sinus Tahycardia and
Atrial Fibrillation)
Transient Ischemic Attack
Unstable Angina Pectoris
Graves’ disease
Subacute thyroiditis
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CARDIOVASCULAR SYSTEM
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Legend: ST – subacute thyroiditis; GD – Graves’ disease; 
BMI – Body Mass Index.
Predictor Odds ratio
(95% confidence 
interval)
p-value
Gender
(0=female, 1=male)
1.44
(0.85–2.44)
0.171
Age 1.02
(1.00–1.04)
0.063
Arterial hypertension
(0=no, 1=yes)
2.83
(1.46–5.48)
0.002
Smoking
(0=no, 1=yes)
1.39
(0.98–1.98)
0.065
Hyperlipidaemia
(0=no, 1=yes)
1.17
(0.41–3.34)
0.763
Diabetes
(0=no, 1=yes)
0.79
(0.44–1.42)
0.427
Increased BMI
(0=no, 1=yes)
2.99
(1.43–6.26)
0.004
TSH 70.61
(0.02–80.4)
0.295
Free T4 1.00
(0.99–1.01)
0.442
Free T3 1.00
(0.98–1.01)
0.817
Thyroid disease
(0=ST, 1=GD)
5.82
(2.07–16.3)
0.001
Table 2: Results of a logistic regression model to test the 
specific effect of independent variables (predictors) on 
cardiovascular complication ocurrence. The Nagelkerke R2 
value of the model was 0.14.
Table 2 shows the results of a logistic regression 
model to test the specific effect of independent vari-
ables on CV complication occurrence. The Nagelkerke 
R2 value of the model was 0.14. GD, AH, and increased 
BMI were found to be independently associated with 
CV complications.
4 Discussion
In our study, the incidence of CV complications in 
a large cohort of hyperthyroid patients with ST or GD 
comparable by age, sex, and BMI was analyzed. A sta-
tistically significantly higher incidence of CV compli-
cations was found in the GD group compared to the ST 
group, and a logistic regression model confirmed that 
the type of thyroid disease, AH, and increased BMI 
were independent predictors of CV complications. To 
our best knowledge, our study is the first to evaluate 
the incidence of CV complications in patients with ST 
compared to patients with GD.
In hyperthyroid patients, increased metabolism, 
oxidative stress, and consequent inflammation lead to 
structural and functional cell and tissue changes that 
affect cardiomyocytes and atrial fibroblasts. These 
changes lead to the development of arrhythmogenic 
zones, including inflammation-induced fibrosis, with 
electrical remodeled cardiomyocytes and consequent-
ly abnormal electrical conduction, ectopy and re-en-
try phenomenon (12). In our study, the most common 
CV complication in patients with GD was AF, which is 
consistent with data from the literature (17). Hyperthy-
roidism is associated with increased oxygen demand in 
the target organs, hyperdynamic circulation, elevated 
systolic blood pressure, and hypercoagulability (6). In a 
patient with a pre-existent non-occlusive atherosclerot-
ic disease, the combination of adverse effects of these 
factors can lead to an acute complication. In our study, 
the incidence of adverse risk factors for CV disease – 
smoking, arterial hypertension, and diabetes was also 
statistically significantly higher in the GD group than 
in the ST group. This finding could explain the higher 
frequency of CV complications other than AF in the 
GD group. Smoking is a known dose-dependent risk 
factor for GD (18-20). Increased systolic blood pres-
sure in hyperdynamic circulation in patients with overt 
hyperthyroidism was reported (9,21,22). One possible 
explanation for the higher incidence of arterial hy-
pertension in the GD group in our study could be the 
more severe hyperthyroidism in this group. The other 
possible reason could be the longer duration of hyper-
thyroidism in the GD group; however, the exact onset 
of either disease could not be estimated and is not re-
ported in the study. Type 1 diabetes and GD are both 
autoimmune endocrine diseases, and the association 
between type 1 diabetes and a higher incidence of GD 
is well documented (23). A higher incidence of hyper-
thyroidism in type 2 diabetes was also reported (24,25).
Systemic inflammation is a known risk factor for a 
higher incidence of sudden CV complications, such as 
AMI (16). The latter event was recorded in our group of 
patients with ST, although it was not statistically more 
frequent than in the GD group. However, the results of 
our study suggest that the severity of hyperthyroidism 
and clustering of adverse CV risk factors contribute to 
CV complications more than systemic inflammation.
In one patient in the GD group, a second-degree 
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ORIGINAL SCIENTIFIC ARTICLE
Cardiovascular complications in hyperthyroid patients with Graves’ disease or subacute thyroiditis
atrio-ventricular (AV) block was recorded, which was 
not an expected finding in a hyperthyroid patient. It 
seems most likely that the patient had an underlying 
disease of the cardiac conduction system or the pres-
ence of one of the other triggers of AV block and that 
this complication was not related to hyperthyroidism.
Only hyperthyroid patients with GD and ST were 
included in our study. Other patients with ST were 
probably already in the second, i.e., recovery phase of 
the disease at the time of diagnosis (2,26,27). In the fi-
nal sample, approximately a quarter of the patients had 
a diagnosis of ST and three-quarters a diagnosis of GD, 
which is also expected in terms of Slovenian popula-
tion incidence – the incidence of GD is between 30–35 
cases/100,000 inhabitants, and the incidence of ST be-
tween 9–10 cases/100,000 inhabitants (2,28,29). The 
ratio between the incidences in the population and in 
both samples is thus 1:3 in favor of GD.
One of the strengths of our study is the large study 
sample. Furthermore, the two groups of patients with 
GD and ST did not significantly differ with respect to 
gender, age and BMI. In compliance with data from 
the literature, the ratio between men and women in 
the sample was about 1:3, which is expected for thy-
roid disease (30). The average age of the patients was 
in the middle age range, which is also in agreement 
with other published data, as both diseases occur most 
often between the ages of 35 and 55 (31). Our study 
deepens the knowledge about the association between 
individual thyroid diseases that cause hyperthyroid-
ism and CV complications (32). Although several ep-
idemiological studies report the association between 
hyperthyroidism and adverse CV complications, large 
epidemiological studies rarely report specific thyroid 
diseases leading to thyroid dysfunction. However, the 
specific pathophysiological mechanisms are different in 
different thyroid diseases (e.g., autoimmune processes 
in GD, systemic inflammation in ST, etc).
One of the weaknesses of our study is its retrospec-
tive nature. Despite the careful review of the patients’ 
paper and electronic documentation, there is a possi-
bility that all the CV complications the patients suf-
fered were not recorded. This influence is estimated to 
be at least partially attenuated by the large number of 
patients included in the study. Furthermore, hospital 
admissions and poorly documented outpatient treat-
ments due to heart failure decompensation, which is 
also a CV complication, could not have been included. 
Also, for methodological reasons, only patients who 
were newly diagnosed with one of the investigated dis-
eases between 2018 and 2021 were included in the re-
search, and not all patients with GD and ST treated at 
our centre during that time period.
5 Conclusion
In conclusion, our study found a higher incidence 
of CV complications in hyperthyroid patients with GD 
in comparison to hyperthyroid patients with ST. Ac-
cording to the results of our study, patients with GD are 
more hyperthyroid and have more adverse risk factors 
for CV disease. 
Conflict of interest
None declared.
Editorial comment
The article was based on Prešeren’s award-winning 
student research paper in 2022.
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