Surviving a Decade or More after Coronary Revascularization in a Middle Eastern Population: The Impact of Diabetes Mellitus.

Introduction: Studies that evaluate Middle Eastern patients who have long-term survival after coronary artery revascularization are scarce. The prevalence of diabetes mellitus (DM) is high and rapidly increasing in our region.
Methods: The study enrolled consecutive ambulatory or in-patients who had percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery at least 10 years earlier. Collected data included cardiovascular risk factors at the time of the index revascularization and evolution of risk factors since then, the occurrence of cardiovascular events, and the need for coronary revascularization after the index procedure. Events were compared between patients with DM and no DM at baseline.
Results: The study population consisted of 891 consecutive patients with 351 patients (39.4%) had DM and 540 patients (60.6%) had no DM. The mean age at baseline was 53.9 ± 8.8 years for DM patients and 53.0 ± 9.8 years for no DM patients (P = 0.16). At baseline, the DM group had more hypertension (70.9% vs. 27.6%, P < 0.0001), more dyslipidemias (12% vs. 5.2%, P = 0.001) but less smokers compared to no DM group (44.4% vs. 58.3%, P < 0.001). DM and no DM groups had similar proportion of PCI (65.5% vs. 68.3%, P = 0.42) and CABG (34.5% vs. 31.7%, P = 0.43) at baseline. Following the index revascularization procedure, acute coronary events, heart failure, and stroke developed in similar proportions in the two groups. Repeat revascularization after the index procedure showed that the DM group had more PCI compared to no DM group (52.7% vs. 45.4%, P = 0.04) but similar proportions of CABG (7.1% vs. 9.8%, P = 0.20). Conclusions: In this retrospective observation of Middle Eastern patients who survived at least a decade after coronary revascularization, the DM group had more hypertension and dyslipidemias but fewer smokers compared to no DM at baseline. During follow-up, the DM group required more PCI revascularization compared with no DM group. Copyright:

INTRODUCTION

Coronary artery disease (CAD) is the leading cause of death in the Middle East[123] and many patients require coronary artery revascularization by either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). Diabetes mellitus (DM) is a major risk factor for the development and progression of CAD and adverse cardiovascular outcomes. The prevalence of DM is high and rapidly increasing in the Middle Eastern region.[4567] There is a scarcity of studies that addressed the impact of DM on the evolution of risk factors and the need for further coronary revascularization after the initial revascularization procedure in the Middle East.

The current study enrolled Middle Eastern patients who had undergone coronary revascularization at least one decade earlier to determine the impact of DM on the prevalence and evolution of cardiovascular risk factors, the occurrence of cardiovascular events, and the need for further coronary revascularizations.

METHODS

We enrolled consecutive Middle Eastern patients who had coronary revascularization by either PCI or CABG at least 10 years before enrollment. Patients were included if they were >18 years old at the time of the index coronary revascularization with available medical records and adequate documentation of patients’ events.

Patients were enrolled during routine outpatient evaluation or in-patient settings when they sought medical care for cardiovascular or noncardiovascular health issues. A case report form for each patient was filled out by the physician assigned by the study steering committee in each participating center. Data were collected from patients, relatives, and medical records according to predefined criteria for each variable. Patients were categorized at the time of the index coronary revascularization as having DM or not having DM. Data were analyzed and compared accordingly for clinical characteristics at baseline, the evolution of cardiovascular risk factors, cardiovascular events, and further coronary revascularization from the time of the index procedure until the time of enrollment.

Cardiovascular risk factors were defined according to the standard definitions published by the American College of Cardiology/American Heart Association.[8] Hypertension was defined as having either systolic blood pressure elevated above 140 mmHg and/or diastolic blood pressure above 90 mmHg on several occasions during the hospital stay, being diagnosed to have hypertension, or being prescribed antihypertension medications by a treating physician.

DM was defined as fasting serum glucose ≥126 mg/dl, 2-h glucose level ≥200 mg/dl, or glycosylated hemoglobin (HbA1c) value ≥6.5%. DM was also diagnosed in patients who had unequivocal hyperglycemia and classical symptoms of DM (polyuria, polydipsia, and unexplained weight loss) and casual plasma glucose >200 mg/dL, and those with a prior diagnosis of DM or who were prescribed antidiabetic medications by a treating physician. Patients who were cigarette smokers at enrollment were considered current smokers. Patients who never smoked and past smokers who quit at least 1 month before enrollment were considered nonsmokers. Family history of premature cardiovascular diseases (CVD) was defined as myocardial infarction, coronary revascularization, or sudden death before 55 years of age in the father or other male first-degree relative, or before 65 years of age in the mother or other female first-degree relative. Hypercholesterolemia was determined by a diagnosis by a physician or/and a lipid-lowering agent prescription, serum cholesterol >200 mg/dL, or low-density lipoprotein cholesterol level >130 mg/dL.

Cardiovascular events that occurred since the index coronary revascularization included (a) acute coronary syndrome (ACS) diagnosed by documented typical chest pain, electrocardiographic changes of ST-segment elevation or depression, T-wave inversion, and with or without elevated cardiac enzymes; (b) heart failure, diagnosed by a physician based on clinical, radiological, and echocardiographic features of left ventricular systolic dysfunction (ejection fraction <40%); (c) stroke, diagnosed by a neurologist; (d) chronic renal impairment, defined as the presence of kidney damage or an estimated glomerular filtration rate <60 ml/min/1.73 m2 persisting for 3 months or more, irrespective of the cause.

Further coronary revascularization included all documented repeat PCI or CABG after the index procedure. The use of guideline-directed secondary cardiovascular prevention medications was documented. Medications included antiplatelet medications (aspirin, clopidogrel, and ticagrelor), beta-blockers, renin-angiotensin system blockers (angiotensin-converting enzyme inhibitors, angiotensin II blockers, and valsartan-sacubitril), lipid-lowering agents (statins, fibrates, and ezetimibe).

The study was approved by the Internal Review Board in all participating centers and informed consent was obtained for all patients.

Statistical analysis

Patients’ characteristics were described using frequency and percentages for categorical variables and in mean ± standard deviation for continuous variables. The differences in percentages between DM and no DM groups were analyzed using the Chi-square test and the differences in the means between the two groups were analyzed using the two-tailed Student's t-test. A P < 0.05 was considered statistically significant. All P values were the results of two-tailed tests.

RESULTS

Table 1 shows baseline clinical characteristics at the time of the index coronary revascularization according to DM status. Patients in the DM group were more likely to have hypertension and dyslipidemia and were less likely to be smokers compared with patients with no DM group. The no DM group had a longer time elapsed from the index revascularization to enrollment compared with the DM group and that was mainly driven by more patients in the no DM who had over 20 years elapsed since the index procedure. There were no significant differences in the other characteristics between the two groups.

Table 1

Baseline clinical characteristics at the time of the index coronary revascularization according to diabetes mellitus status

Clinical feature	DM (n=351; 39.4%), n (%)	No DM (n=540; 60.6%), n (%)	P
Age at first coronary revascularization (years)	53.9±8.75	53.0±9.82	0.164
≤45	51 (14.5)	98 (18.1)	0.578
>45	300 (85.5)	442 (81.9)	0.196
Coronary revascularization at baseline
PCI	230 (65.5)	369 (68.3)	0.399
CABG surgery	121 (34.5)	171 (31.7)	0.426
Years since the first coronary revascularization	13.5±3.5	14.4±4.8	0.025
10	105 (29.9)	149 (27.6)	0.689
11-20	235 (67)	339 (62.8)	0.301
>20	11 (3.1)	52 (9.6)	<0.001
Women	69 (19.7)	54 (10)	<0.001
Hypertension	249 (70.9)	149 (27.6)	<0.001
Dyslipidemia	42 (12)	28 (5.2)	<0.001
Cigarette smoking	157 (44.4)	315 (58.3)	<0.001
Family history of premature CAD	30 (8.5)	35 (6.5)	0.252

CAD: Coronary artery disease, PCI: Percutaneous coronary intervention, CABG: Coronary artery bypass graft, DM: Diabetes mellitus

Table 2 demonstrates the evolution of major risk factors and the development of major adverse events among the two groups from the index procedure till enrollment. The no MD group was more likely to develop hypertension compared to the DM group. There were no significant differences in the evolution of other risk factors of clinical events among the two groups.

Table 2

Emerging risk factors and cardiovascular events since the first coronary revascularization

Event	DM, n (%)	No DM, n (%)	P
Emerging risk factors after the initial procedure
No DM initially developed DM	-	167 (30.9)	-
Developed hypertension	33 (9.4)	107 (19.8)	<0.001
Became smoker	2 (0.6)	3 (0.6)	1.000
Quit smoking	70 (19.9)	129 (23.9)	0.519
Cardiovascular events after the initial procedure
Acute coronary syndrome	143 (40.7)	225 (41.7)	0.820
Congestive heart failure	44 (12.5)	72 (13.3)	0.511
Stroke	16 (4.6)	32 (5.9)	0.748
Renal failure	7 (2)	19 (3.5)	0.479

DM: Diabetes mellitus

Table 3 summarizes the need for further coronary revascularization after the index procedure till enrollment. The DM group was more likely to require PCI procedures compared to no DM group. CABG was required similarly in the two groups.

Table 3

Repeat coronary revascularization after the index procedure

Procedure	DM, n (%)	No DM, n (%)	P
PCI
Total patients	184 (52.4)	246 (45.6)
One occasion	106 (30.2)	152 (28.1)	0.039
Two occasions	45 (12.8)	71 (13.1)
Three or more occasions	33 (9.4)	23 (4.3)
CABG
Total patients	25 (7.1)	53 (9.8)
One occasion	25 (7.1)	51 (9.4)	0.202
Two occasions	0	2 (0.4)
Three or more occasions	0	0

PCI: Percutaneous coronary intervention, CABG: Coronary artery bypass graft, DM: Diabetes mellitus

Table 4 shows cardiometabolic medications used in diabetic versus nondiabetic patients at the time of enrollment. In general, there was a high utilization of guideline-directed secondary preventive therapies with no significant difference between the two groups except for higher utilization of clopidogrel in the DM group compared to no DM.

Table 4

Utilization of cardiometabolic medications at enrollment

Medication	DM, n (%)	No DM, n (%)	P
Aspirin	295 (92)	449 (89.6)	0.609
Second antiplatelet agent
Clopidogrel	124 (38.6)	175 (34.9)	0.023
Ticagrelor	16 (5)	13 (2.6)	0.081
Beta-blocker	257 (80)	383 (76.4)	0.192
ACEI or ARB	190 (54.1)	292 (54)	1.000
Lipid-lowering agent
Statin	287 (89.4)	459 (91.4)	0.355
Fibrate	9 (2.8)	23 (4.6)	0.327
Ezitimibe	3 (0.9)	10 (2)	0.935
Combination	3 (0.9)	2 (0.4)	0.948

ACEI: Angiotensin-converting enzyme inhibitor, ARB: Angiotensin receptor blocker, DM: Diabetes mellitus

DISCUSSION

This is the first report, up to our knowledge, that addressed the impact of DM on the prevalence and evolution of cardiovascular risk factors, the occurrence of cardiovascular events, and the need for further coronary revascularizations among long-term survivors of coronary revascularization in a Middle Eastern population. Almost 40% of the study population had DM at baseline with close to an additional 30% developed DM during the elapsed time between the index procedure and enrollment. This finding speaks to the alarmingly high prevalence of DM in our region. With the addition of the high smoking rate among our population, it is not surprising to see the baseline index revascularization was performed at a very young age compared to the Western population.

The DM group required more repeat PCI compared to the no DM group; however, CABG and adverse cardiovascular outcomes were similar among the two groups. This may be related to the retrospective nature of the current study and the longer time elapsed after the index revascularization in the no DM group. The retrospective nature of this study may have downplayed or missed more serious adverse events in the DM group like mortality or major disability that prevents enrollment of such patients. This is partially supported by the longer time elapsed after the index revascularization in the no DM group, thus many adverse events and repeat revascularizations are related to the time factor diminishing the impact of DM. Furthermore, extended survival in this report after the index revascularization could be related to a relatively young age of patients at the time of index procedure, adoption of contemporary percutaneous and surgical coronary revascularization strategies, and the high utilization of secondary cardiovascular prevention medications.

The global burden of DM has more than doubled over the past three decades[5] with a greater escalation over the same period seen in the Middle East.[456] The ascending trends of DM prevalence in our region lead to more premature heart disease, stroke, and other vascular disorders.[910] CVD had become the leading cause of death in the Middle East,[12310] with almost one to two-thirds of patients admitted with ACS being diabetics.[111213] These alarming trends in the prevalence of DM and premature CVD in the region should be addressed and overturned through national and regional preventive health policies.

Coronary atherosclerosis in patients with DM is usually diffuse and rapidly progressive disease. Revascularization in these patients is usually faced with augmented risk related to DM itself, type of treatment, and the angiographic complexity of CAD. Thus, it is not surprising to find that DM patients required more coronary revascularization compared to no DM.[141516]

Limitations

The major limitation of the study is inherited in its retrospective design. Enrollment was limited to patients encountered after at least 10 years after coronary revascularization. The information may be affected by survival bias, random selection, and lack of prospective controlled data collection.

CONCLUSIONS

In this retrospective observation of Middle Eastern patients who survived at least a decade after coronary revascularization, the initial revascularization procedure was performed at a younger age compared to the Western population mostly related to an abundance of risk factors. Almost 40% of the population had DM at baseline and an additional 30% acquired DM during the elapsed time. During follow-up, the DM group required more PCI revascularization compared with no DM group. Preventive strategies targeting the Middle East populations are essential to minimize the burden of the disease and its consequences.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.