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Abstract

Objective

Long-standing diabetes mellitus is often associated with cardiovascular complications. We aimed to evaluate the presence, extent and composition of subclinical atherosclerotic plaques in coronary arteries by Computed Tomography in patients with newly diagnosed type 2 diabetes mellitus (NDT2DM), and to identify the predictors.

Methods

In this study 101 consecutive patients with NDT2DM were included. Patients were categorized into five groups based on their Coronary Artery Calcium Score (CACS) ranging from 0, 0-10, 11-100, 101-400 to >400. All parameters were compared across these groups.

Results

The average patient age was 54.4 ± 11.6 years and 48 (47.5%) were females. Eight (7.9%) patients had CACS 0, 6.9% CACS 1-10, 42.6% CACS 11-100, 22.8% CACS 101-400 and 19.8% had CACS >400. Multiple regression analysis for the general data identified weight (p = .04) and systolic blood pressure (p = .033) as independent predictors for CACS.

Conclusions

Asymptomatic patients with NDT2DM in more than 90% of cases may present with calcified atherosclerotic plaques and this may be predicted by: patient weight and the level of systolic arterial pressure. Our study emphasizes the need for comprehensive care and early prevention of cardiovascular complications in individuals with NDT2DM.

Keywords

Newly diagnosed type 2 diabetes mellitus coronary artery calcium score body weight arterial hypertension erythrocyte sedimentation rate

Introduction

In 2021 the global prevalence of type 2 diabetes mellitus (T2DM) among 20-79 year olds was estimated to be 10.5% (536.6 million people), while in 2045 it is expected to increase to 12.2% (783.2 million).¹ About half of all patients suffering from diabetes are undiagnosed.²

Studies indicate that individuals can experience an asymptomatic pre-diabetes and T2DM phase for 5-6 years before receiving a diagnosis.³ Throughout this period, there is a possibility of the development of micro- and macrovascular complications.⁴ However, complications generally appear after long-standing diabetes mellitus.

The calcium score in the coronary arteries is a reliable predictor of coronary heart disease events. It has become a widely available, accurate, and dependable tool for determining the risk of major cardiovascular events, particularly in asymptomatic individuals.⁵

The aim of this study was to assess the presence, extent and composition of subclinical atherosclerotic plaques in coronary arteries by means of Computed Tomography in patients with NDT2DM, asymptomatic for cardiac disease, as well as to identify the predictors for their emergence.

Material and methods

This was a prospective cross-sectional study conducted in our tertiary health care center from October 2019 until December 2022, which included 101 consecutive patients with NDT2DM and without cardiovascular symptoms. Diabetes mellitus was diagnosed according to American Diabetes Association (ADA) criteria. Demographic and history data, physical examination, basic laboratory tests, and coronary artery calcium score (CACS) were obtained for each patient. Among the laboratory tests, we included: erythrocyte sedimentation rate, red blood cell count, white blood cell count, hemoglobin level, hematocrit, platelet count, blood urea nitrogen, creatinine, glycaemia, cholesterol, triglyceride, and HbA1c level.

Exclusion criteria included patients with stable angina pectoris, acute coronary artery disease, severe anemia, patients with history of stroke, moderate/severe renal insufficiency, liver insufficiency, patients in whom adequate heart rate could not be obtained prior to CACS procedure, claustrophobic patients, and pregnant women. Only one patient was excluded due to inability to achieve adequate heart rate.

CACS was performed on all patients by 64-slice cardiac computed tomography (Brilliance 64; Philips Medical Systems, Best), with a thickness of 2-5 mm. Calcification was identified as a structure >1 mm attached to or located within the lumen of a coronary vessel with intensity >130 HU. The patients' heart rate was reached below 65 beats per minute during the procedure. The Agatston method was used to determine the CACS score. CACS 0 reflects absent risk for coronary artery disease, 1-10 minimal, 11-100 mild, 101-400 moderate and >400 suggests high risk for developing coronary artery disease (such as myocardial infarction) in the near future. Calcium Volume Score was calculated by multiplying the number of calcified voxels by the volume of each voxel, considering all voxels with an attenuation more significant than 130 HU. The relative calcium mass score was calculated by multiplying the calcified plaque’s mean attenuation by the plaque volume in each image.⁶

The patients were categorized into five groups based on their calcium levels and all parameters were subsequently compared across these groups.

The research received approval from our institution’s Ethical Board, and written informed consent was obtained from each participant.

Statistical analysis

The data were analyzed with the statistical package SPSS Statistics 22.0 Software (IBM, Chicago, IL, USA). Data were presented as percentage, mean and standard deviation. Qualitative variables were tested with chi-square test or Fisher’s exact test. Quantitative variables with normal distribution were tested with Student's T-test or One Way ANOVA, while those with non-normal distribution with Mann-Whitney test or Kruskal Wallis test. Spearman’s correlation and multiple regression analysis were also calculated. The statistical difference was considered significant if p < .05.

Results

Of the 101 asymptomatic patients with NDT2DM, 48 (47.5%) were female, the average age of the patients was 54.4 ± 11.6 years. The risk factors were as follows: arterial hypertension 61.4%, smokers 37.6%, dyslipidemia 36.6%, positive family history for coronary artery disease 34.7%, body mass index 31.0 ± 5.6 kg/m2, while time since diagnosis of T2DM was 2.8 ± 5.3 months. Only 8 (7.9%) patients did not have calcified atherosclerotic plaques or had a CACS of zero, 7 (6.9%) patients had a CACS of 1-10, 43 (42.6%) patients had a CACS of 11-100, 23 (22.8%) patients had CACS 101-400 and 20 (19.8%) patients had CACS >400 (Figure 1). The mean total volume and mass of calcium in these patients was 210 and 180, respectively. LAD had the highest CACS score, followed by RCA, LCx and left main coronary artery.

Figure 1.

Coronary Artery Calcium Score (CACS) with high amount of calcium in the coronary arteries in our patient with newly diagnosed type 2 diabetes mellitus (total CACS: 7587).

In Table 1 the differences between the five groups are depicted. As shown in Table 2, our analysis using Spearman’s correlation revealed a significant correlation between the CACS and a few general parameters, although some of these correlations exhibited weak statistical power. With multiple regression analysis, we evaluated the impact of the general data on the CACS values. In the model with 13 parameters, we found that all of them together had a 16.6% impact on the CACS, without a synergistic impact (p = .210). In this model, weight (p = .04) and systolic blood pressure (p = .033) had a significant impact (Table 2).

Table 1.

Comparison of general characteristics of the patients included in the study according to the groups.

Parameters Mean ± SD; N(%)	CACS					p-value
Parameters Mean ± SD; N(%)	0	1-10	11-100	101-400	>400
Total	8	7	43	23	20
Gender, Females	3 (37.5%)	7 (100.0%)	21 (48.8%)	7 (30.4%)	10 (50.0%)	.028
Gender, Males	5 (62.5%)		22 (51.2%)	16 (69.6%)	10 (50.0%)
Age	49.5 ± 11.8	51.9 ± 10.8	50.8 ± 11.7	55.3 ± 9.8	64.1 ± 7.7	.0002
Smokers	3 (37.5%)	3 (42.9%)	16 (37.2%)	10 (43.5%)	6 (30.0%)	.922
Hypertension	1 (12.5%)	5 (71.4%)	23 (53.5%)	16 (69.6%)	17 (85.0%)	.005
DM-duration (months)	2.3 ± 2.8	0.4 ± 0.3	2.6 ± 2.5	2.5 ± 2.4	2.0 ± 1.8	.0837
Family history for CAD		4 (57.1%)	18 (41.9%)	9 (39.1%)	4 (20.0%)	.063
Dyslipidemia			19 (44.2%)	8 (34.8%)	10 (50.0%)	.023
BMI (kg/m2)	30.2 ± 6.2	28.2 ± 5.1	30.7 ± 4.6	33.1 ± 6.7	30.8 ± 5.8	.5025
Waist (cm)	91.9 ± 14.5	86.4 ± 7.7	96.3 ± 10.1	102.3 ± 12.8	97.3 ± 8.3	.0092
Hips (cm)	99.8 ± 11.0	98.3 ± 6.8	104.5 ± 9.1	107.6 ± 11.2	106.9 ± 9.0	.0906
SAP (mmHg)	115.6 ± 11.8	119.3 ± 10.2	121.6 ± 15.2	129.3 ± 18.0	132.3 ± 24.5	.0999
DAP (mmHg)	71.3 ± 8.3	77.9 ± 9.1	78.4 ± 8.9	80.9 ± 9.0	81.3 ± 9.4	.1126

DM: diabetes mellitus; CAD: coronary artery disease; BMI: body mass index; SAP: systolic arterial pressure; DAP: diastolic arterial pressure. The significance for the use of bold is for p < 0.05.

Table 2.

The Spearman correlation between CACS and general data, and CACS predictors.

Parameters	CACS
Parameters	r (95% CI)	p-value
Smoker	r = −0.0487 (95% CI -0.247-0.154)	.628
Arterial hypertension	r = 0.282(95% CI 0.086-0.457)	.004
Duration of DM (months)	r = 0.0407 (95% CI -0.162-0.239)	.686
Positive family history for CAD	r = 0.069 (95% CI -0.266 - 0.133)	.491
Dyslipidemias	r = 0.230 (95% CI 0.031 - 0.412)	.020
BMI (kg/m2)	r = 0.062 (95% CI -0.140 - 0.261)	.531
Waist/hip ratio	r = 0.091 (95% CI -0.113 - 0.286)	.367
Systolic arterial pressure	r = 0.281 (95% CI 0.085-0.456)	.004
Diastolic arterial pressure	r = 0.232 (95% CI 0.032-0.414)	.019
Heart rate	r = −0.121 (95% CI -0.315 - 0.081)	.227

Parameters	t-ratio	p-value
CACS	1.325	.1886
Smokers	0.1765	.8603
Arterial hypertension	0.2196	.8267
Duration of DM (months)	0.6674	.5063
Positive family history for CAD	0.9349	.3524
Dyslipidemias	0.8134	.4182
Body height	1.783	.0781
Body weight	2.078	.0406
BMI (kg/m2)	1.797	.0759
Waist (cm)	0.5016	.6172
Hips (cm)	0.5706	.5697
Waist/Hip ratio	0.527	.5995
Systolic arterial pressure	2.165	.0331
Diastolic arterial pressure	0.037	.9703

CACS: Coronary artery calcium score; DM: diabetes mellitus; CAD: coronary artery disease; BMI: body mass index. The significance for the use of bold is for p < 0.05.

The basic laboratory results, with exception of erythrocyte sedimentation rate, did not reveal significant difference between the five groups. The difference of erythrocyte sedimentation rate starting from 0 CACS to the most severe CACS group was as follows: 18.1 ± 21.5 mm/h, 20.1 ± 27.4 mm/h, 23.7 ± 22.9 mm/h, 29.2 ± 20.7 mm/h and 26.3 ± 18.8, p = .044. The correlation between CACS and laboratory parameters, showed significance for the erythrocyte sedimentation rate [r = 0.280 (95% CI 0.083-0.455), p = .0046] and triglyceride level [r = 0.196 (95% CI -0.005 - 0.382), p = .049]. Whereas, the multiple regression model for laboratory results revealed that the 12 parameters that were used had a 32.8% influence in CACS, without significance (p = .561). None of the laboratory parameters were shown to be independent predictors.

Discussion

In our study, asymptomatic patients with NDT2DM in more than 90% of cases presented with some degree of calcium burden determined by CACS, while the most loaded artery was the LAD. Whereas, in random population of age groups 45–54 years and 55-64 years, CACS 0 was shown in 51% and 36% of patients, respectively.⁷ These figures differ largely from our results in NDT2DM patients. Screening of CACS in asymptomatic persons with diabetes mellitus may more promptly and reliably identify those at highest risk who could benefit from intensified therapeutic options.⁸ A small number of studies have analyzed cardiac complications in patients with NDT2DM without cardiac symptoms. The VALIANT (VALsartan In Acute myocardial iNfarcTion) trial showed that 3400 patients with previously known diabetes had similar risk of mortality and cardiovascular events as 580 patients with NDT2DM.⁹

Our data showed that there were significant differences between the CACS groups regarding gender, age, arterial hypertension, dyslipidemia and waist circumference, whereas there was significant correlation between CACS level and arterial hypertension, dyslipidemias, systolic and diastolic arterial pressure. Patient weight and systolic arterial pressure were shown to be independent predictors for CACS among this category. Raggi et al suggest that high age- and sex-adjusted CACS percentiles appear to be closely related to the occurrence of subsequent hard events.¹⁰ CACS equal to zero does not reliably exclude obstructive CAD in younger patients, who are known to have a higher burden of non-calcified plaque.¹¹ Regarding weight, similarly to our results Lim et al. suggest that a greater rate of prior weight gain may accelerate the development of subclinical vascular complications depicted by CACS in patients with NDT2DM.¹² Tomizawa et al. compared severity and extent of coronary artery plaques in 1161 patients with either hypertension, diabetes mellitus or dyslipidemia and it resulted that patients with diabetes mellitus had more extensive disease than hypertension and dyslipidemia patients.¹³ However, CACS was similar in patients with hypertension and diabetes mellitus. Moreover, recent findings indicate that the coexistence of T2DM and hypertension not only elevates the risk of partially calcified plaques but also contributes to the extent of coronary artery disease.¹⁴ This explains the fact that in our study arterial hypertension and in particular systolic arterial pressure predicts CACS in patients with NDT2DM.

Erythrocyte sedimentation rate was shown to correlate with CACS in our patients. Several other authors have demonstrated that erythrocyte sedimentation rate is a predictor of both coronary atherosclerosis and mortality associated with coronary heart disease.^15,16 Similar to our findings, other researchers have reported elevated triglyceride levels in individuals with diabetes mellitus undergoing assessment for CACS.^17,18

Conclusions

In over 90% of cases, asymptomatic individuals with NDT2DM may present with calcified atherosclerotic plaques identified by CACS, and nearly half of these patients fall into the second category of calcium burden. Predictors for the calcium burden in coronary arteries in our patients with NDT2DM are patient weight and the level of systolic arterial pressure. Our study emphasizes the significance of comprehensive care for individuals with NDT2DM. In addition to maintaining glycemic control, there is a crucial need for early prevention of cardiovascular complications.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Shpend Elezi

Aurora Bakalli

References

Sun

Saeedi

Karuranga

, et al. IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 2022; 183: 109119.

Stadler

Prager

. Typ 2 Diabetes mellitus--Screening und Prävention [Type 2 diabetes mellitus--screening and prevention]. Acta Med Austriaca 2004; 31(5): 158–159.

Heydari

Radi

Razmjou

, et al. Chronic complications of diabetes mellitus in newly diagnosed patients. Int J Diabetes Mellit 2010; 2: 6163.

Gedebjerg

Almdal

Berencsi

, et al. Prevalence of micro- and macrovascular diabetes complications at time of type 2 diabetes diagnosis and associated clinical characteristics: a cross-sectional baseline study of 6958 patients in the Danish DD2 cohort. J Diabetes Complications 2018; 32(1): 34–40.

Shreya

Zamora

Patel

, et al.

Coronary artery calcium score - a reliable indicator of coronary artery disease?

Cureus 2021; 13(12): e20149.

McCollough

Ulzheimer

Halliburton

, et al. Coronary artery calcium: a multi-institutional, multi-manufacturer international standard for quantification at cardiac CT. Radiology 2007; 243(2): 527–538.

Blaha

Silverman

Budoff

. Is there a role for coronary artery calcium scoring for management of asymptomatic patients at risk for coronary artery disease? Clinical risk scores are not sufficient to define primary prevention treatment strategies among asymptomatic patients. Circ Cardiovasc Imaging 2014; 7(2): 398–408.

Tehrani

Malik

Wong

. Coronary artery calcium screening in persons with metabolic syndrome and diabetes: implications for prevention. Metab Syndr Relat Disord 2013; 11(3): 143–148.

Aguilar

Solomon

Køber

, et al. Newly diagnosed and previously known diabetes mellitus and 1-year outcomes of acute myocardial infarction: the VALsartan in Acute myocardial iNfarcTion (VALIANT) trial. Circulation 2004; 110(12): 1572–1578.

10.

Raggi

Callister

Cooil

, et al. Identification of patients at increased risk of first unheralded acute myocardial infarction by electron-beam computed tomography. Circulation 2000; 101(8): 850–855.

11.

Sheppard

Lakshmanan

Lichtenstein

, et al. Age and the power of zero CAC in cardiac risk assessment: overview of the literature and a cautionary case. Br J Cardiol 2022; 29(3): 23.

12.

Lim

Choi

Kim

, et al. The association of rate of weight gain during early adulthood with the prevalence of subclinical coronary artery disease in recently diagnosed type 2 diabetes: the MAXWEL-CAD study. Diabetes Care 2014; 37(9): 2491–2499.

13.

Tomizawa

Nojo

Inoh

, et al. Difference of coronary artery disease severity, extent and plaque characteristics between patients with hypertension, diabetes mellitus or dyslipidemia. Int J Cardiovasc Imag 2015; 31(1): 205–212.

14.

Jiang

Shi

, et al. The additive effect of essential hypertension on coronary artery plaques in type 2 diabetes mellitus patients: a coronary computed tomography angiography study. Cardiovasc Diabetol 2022; 21(1): 1.

15.

Natali

L'Abbate

Ferrannini

. Erythrocyte sedimentation rate, coronary atherosclerosis, and cardiac mortality. Eur Heart J 2003; 24(7): 639–648.

16.

Erikssen

Liestøl

Bjørnholt

, et al. Erythrocyte sedimentation rate: a possible marker of atherosclerosis and a strong predictor of coronary heart disease mortality. Eur Heart J 2000; 21(19): 1614–1620.

17.

Salem

Moneir

Adly

, et al. Study of coronary artery calcification risk in Egyptian adolescents with type-1 diabetes. Acta Diabetol 2011; 48(1): 41–53.

18.

Gunczler

Lanes

Soros

, et al. Coronary artery calcification, serum lipids, lipoproteins, and peripheral inflammatory markers in adolescents and young adults with type 1 diabetes. J Pediatr 2006; 149(3): 320–323.

Predictors of coronary artery calcium burden in asymptomatic patients with newly diagnosed type 2 diabetes mellitus

Abstract

Objective

Methods

Results

Conclusions

Keywords

Introduction

Material and methods

Statistical analysis

Results

Discussion

Conclusions

Footnotes

Declaration of conflicting interests

Funding

ORCID iDs

References