Assessment of coronary heart diseases in diabetics in al-Madinah al-Munawarah.

BACKGROUND: Coronary heart disease is highly prevalent and a major cause of morbidity and mortality in diabetic patients. The aim of this study was to assess the major risk factors and their predictor score for coronary heart diseases in diabetic patients.
METHODS: The present study was conducted in al-Madinah, Kingdom of Saudi Arabia. Using a cross-sectional case control study, 262 outpatient diabetics and 264 matched control subjects were examined for the risk factors and risk predictor scores for ischemic heart disease. The mean age of the patient and control groups was 49.61 ± 12.93 years and 48.39 ± 11.60 years, respectively.
RESULTS: Diabetic patients had significantly higher positive family history of diabetes, but no significant difference regarding their family history of hypertension. There was a significantly higher body mass index (33.67 kg/m(2)), glycosylated hemoglobin (7.26%), significantly higher cholesterol, low-density lipoprotein, and triglyceride in diabetics compared to control. Diabetic patients had higher risk for developing coronary heart disease with a mean risk score of 6.07 while the control subject risk score was -6.81. However, females showed significantly higher risk for coronary heart diseases than did males.
CONCLUSION: Our study replicates the known fact of higher risk in diabetes, but higher risk of coronary heart disease in female diabetics compared with male diabetics.

Introduction

Cardiovascular disease is the leading cause of death among patients either with type I or type II diabetes mellitus (DM).1 The prevalence of coronary heart disease (CHD) is 5.5% in the Kingdom of Saudi Arabia, with a prevalence in males and females of 6.6% and 4.4%, respectively. Urban Saudis have a higher CHD prevalence (6.2%) compared to rural Saudis (4%).2 Patients with diabetes, but without other conventional risk factors for atherosclerosis, have a risk of death from CHD 2–4 times that of age-matched controls.3 Those with type II DM commonly have other associated risk factors, such as hypertension or dyslipidemia, thus further increasing their cardiovascular risk. Women with diabetes have an increased risk of cardiovascular death of up to 7.5 times that of nondiabetic women. Diabetic women do not have the premenopausal benefit seen in the general female population.3–5

Individuals with diabetes and CHD fare worse than do other patients with CHD. Those who present with a myocardial infarction (MI) are at increased risk of dying from their event or of developing heart failure.6,7 They benefit less from thrombolysis in the setting of an acute MI.5,6,8 Coronary artery bypass surgery and percutaneous transluminal coronary angioplasty are associated with greater long-term mortality in diabetic patients than in those without diabetes.7,9,10 Therefore, prevention or early detection of CHD is important to ensure early medical interventions to improve outcome.

The past decade has witnessed major strides in the prevention of CHD through modification of its causes. The most dramatic advance has been the demonstration that aggressive medical therapy will substantially reduce the likelihood of recurrent major coronary syndromes in patients with established CHD (secondary prevention). The American Heart Association (AHA) and the American College of Cardiology (ACC) have published joint recommendations for medical intervention in patients with CHD and other forms of atherosclerotic disease.11,12

The present statement is being published jointly by the AHA and ACC to outline current issues and approaches to global risk assessment for primary prevention. The approaches described in this statement can be used for guidance at several levels of primary prevention; however, the statement does not attempt to specifically link risk assessment to treatment guidelines for particular risk factors. Nonetheless, it provides critical background information that can be used in the development of new treatment guidelines.13,14

The quantitative relationship between these risk factors and CHD risk has been elucidated by the Framingham Heart Study.14 The predisposing risk factors are those that worsen the independent risk factors. Two risk factors, obesity and physical inactivity, are designated major risk factors by the AHA.15,16 The adverse effects of obesity are worsened when it is expressed as abdominal obesity,15 an indicator of insulin resistance.

The other predisposing risk factors are obesity, physical inactivity, and family history of premature CHD, ethnic characteristics, psychosocial factors, elevated serum triglycerides, elevated serum homocysteine, prothrombotic factors, and inflammatory markers.

The elevated inflammatory biomarkers such as high-sensitivity C-reactive protein predict CHD diseases,17 and death independently of other cardiovascular risk factors.18

Methods

This is a case-control study carried out in al-Madinah al-Munawarah, Kingdom of Saudi Arabia. The study was approved by the Scientific Research Deanship committee of Taibah University. Informed consent was obtained from all participants. The aim of this study was to assess the major risk factors and their predictor score for CHDs in diabetic patients.

Patients

The study included 526 subjects, who were sorted into two groups: Group A included 262 patients (118 males and 144 females) diagnosed as diabetics according to the American Diabetes Association (ADA) definition of diabetes, and who were selected by using a simple random sample at the outpatient clinic of the Diabetic Patients Center in King Fahad Hospital; a matched Group B for age and sex included 264 patients (122 males and 142 females) with no diabetes or cardiac problems, who were randomly selected from other outpatient clinics.

Blood analysis

Each subject in both groups provided demographic data using a structured questionnaire in Arabic. All subjects were examined clinically and information pertaining to age, sex, habits, and health status was recorded. Weight was measured in kilograms using a standard beam scale with subjects barefoot and wearing light clothes. Weight was recorded to the nearest 100 g. Height was measured in centimeters on a calibrated height board attached to the beam scale. Obesity was assessed using body mass index (BMI) and patients were classified as overweight (BMI = 25.0–29.9 kg/m2), obese (BMI = 30.0–39.9 kg/m2), and morbid obesity (BMI = 40.0 kg/m2).16

Blood samples were collected from both control and patient groups for a series of laboratory investigations using standard protocols for estimation of fasting and postprandial blood glucose, serum total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, serum creatinine, and glycosylated hemoglobin (HbA1C) (Bio-Rad DiaSTAT Hemoglobin A1C Program; Bio-Rad Laboratories, Hercules, CA). The normal range for people without diabetes (4.4%–6.4%) was estimated. HbA1Cof <7% was considered as good glycemic control, and above 7% considered as poor control.19,20 Cholesterol levels below 5.18 mmol/L of blood were considered normal, between 5.18 and 6.18 mmol/L were considered borderline high, and above 6.18 mmol/L were high. Triglyceride levels <150 mg/dL (<1.7 mmol/L) were defined as normal, 150–200 mg/dL (1.7–2.3 mmol/L) as increased risk, and >200 mg/dL (>2.3 mmol/L) as high risk. HDL levels >40 mg/dL (>1.04 mmol/L) were taken as normal and a desirable level, between 30–40 mg/dL as increased risk, and <30 mg/dL as high risk. LDL levels were optimal if less than 100 mg/dL (<1.3 mmol), borderline high at 130–159 mg/dL (3.3–4.1 mmol), and high >160–189 mg/dL (>4.1 mmol).21–24

The major independent risk factor assessed was cigarette smoking. Smoking was classified as current smokers, ex-smokers (having stopped at least 1 year before),25 and nonsmokers. Another independent risk factor was elevated blood pressure; two readings of blood pressure were made on the right arm using a standard mercury sphygmomanometer in the physician’s consulting room after the person was seated for 5 minutes. Hypertension was defined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Elevated serum, total cholesterol, LDL cholesterol, low serum HDL cholesterol, DM, and advancing age were also considered risk factors. The Global Risk Assessment Score and the low-risk state were defined according to the Framingham Heart Study.14

Statistical analysis

Data were analyzed using SPSS software (v. 13; SPSS Inc, Chicago, IL). Descriptive statistics (mean, standard deviation, frequency, and relative frequency) were used to describe demographic and observational data. Student’s t-test for continuous variables was used.

Results

The mean age value was 49.61 ± 12.93 years and 48.39 ± 11.60 years in patient and control groups, respectively. Both groups were matched by number, sex, mean age, nonsmokers, and family history of hypertension and diabetes. The results show that diabetic patients have higher family history of diabetes, while the analysis showed no significant differences regarding family history of hypertension (Table 1).

Table 1

Distribution of the descriptive statistics data of the family history of hypertension and diabetes mellitus in patient and control groups

History	Number of patients
	Patients	Control	Total
Family history of hypertension
Negative	186	191	377
Positive	76	73	149
Family history of diabetes mellitus
Negative	135*	151	286
Positive	127	117	240

Note:

P ≤ 0.05.

Though both groups were obese, BMI in diabetics (33.63 ± 5.97 kg/m2) was more than in control group (31.05 ± 6.76 kg/m2), where there was a highly significant difference (P < 0.001). Statistical analysis shows that there were highly significant differences (Figure 1) in fasting, postprandial blood glucose and glycosylated hemoglobin measurements among both groups. Diabetics had higher fasting and postprandial blood glucose mean values (222.79 and 236.16 mg/dL, respectively). An analysis of variance test showed this was highly statistically significant (P < 0.001). On the other hand, HbA1C was also high in the diabetic group (7.26%) compared to the control (5.58%) and this was highly significant (P < 0.001) (Table 2).

Figure 1

Body mass index for patient and control groups.

Table 2

Distribution of the descriptive statistics of the fasting and postprandial blood glucose and HbA1C in patient and control groups

	Patients (Mean ± SD)	Control (Mean ± SD)
Fasting blood sugar (mg/dL)	86.49 ± 9.34***	85.45 ± 9.04
Postprandial blood sugar (mg/dL)	110.82 ± 25.35***	78.40 ± 9.31
Glycosylated hemoglobin (%)	7.26 ± 1.36***	5.58 ± 0.81

Notes: Significance at ***P ≤ 0.001

Abbreviations: HbA1C, glycosylated hemoglobin; SD, standard deviation.

We found that the mean systolic and diastolic blood pressure values for diabetics were highest, at 137.39 ± 20.98 mmHg and 81.29 ± 10.12 mmHg, respectively, compared to 115 ± 18 mmHg and 72 ± 13 mmHg for the control group, which was highly statistically significant (P < 0.005) (Figure 2).

Figure 2

Blood pressure for patient and control groups.

Figure 3 shows the blood lipid profile (total cholesterol, HDL, LDL, and triglycerides) measures for both groups. Diabetes patients had higher LDL levels, where the mean was 3.21 ± 0.98 mmol/dL (P < 0.005). On the other hand, regarding total cholesterol, LDL, triglycerides, and HDL there were no significant differences between diabetic and control groups (P > 0.05).

Figure 3

Lipid profile for patient and control groups.

Abbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein; T. Chol., total cholesterol; TG, triglycerides.

Figure 4 shows the total risk for patient and control groups. Diabetics have a higher total risk (2.57) compared to the control (−6.81) and this was highly statistically significant (P < 0.001).

Figure 4

Total mean risk values for subjects in patient and control groups.

Figure 5 shows the sex differences for patient and control groups. Female subjects in the diabetic group have a significantly higher risk for coronary disease as their risk prediction score within 10 years was 5% compared to 2% for males, while the coronary disease risk prediction score within 10 years in the control group was 1% for both males and females.

Figure 5

CHD risk prediction score for patient and control groups according to sex.

Abbreviation: CHD, coronary heart disease.

Discussion

This study was carried out to evaluate the risk factors of CHD in diabetic patients through demographic data, health habits, and anthropometric and biochemical profiles.

DM is known to be associated with a high risk of developing vascular complications that can lead to premature death and/or disability mainly by increasing the risk of MI, stroke, and peripheral vascular disease.26 Moreover, the National Cholesterol Education Program report from United States and guidelines from Europe consider type II diabetes to be a CHD equivalent, thereby elevating it to the highest risk category.27 Patients with DM are two to four times more likely to develop cardiovascular disease than those in the general population and have two to five times greater risk of dying from these diseases.28,29 There is now growing consensus that nondiabetic hyperglycemia measured by fasting glucose, postload glucose or HbA1C is a progressive, continuous risk for cardiovascular outcomes.30 Apart from the traditional risk factors such as hypertension, hyperlipidemia, and obesity, hyperglycemia is an independent risk factor for the development of ischemic heart disease. Long-term hyperglycemia leads to vascular damage through several mechanisms as oxidative stress, formation of advanced glycation end products, activation of nuclear factor kappa B, and decreased production of nitrogen monoxide.31

Despite most of our patients having almost normal fasting and postprandial blood sugar levels (86.49 ± 9.34 mmHg and 110.82 ± 25.35 mmHg, respectively), they still have increased risk for death from ischemic heart disease as they are already known to be diabetic and their HbA1C was 7.2 6 ± 1.36 mmHg. These still could be explained by Honolulu Heart Program, where they found that the deaths from CHD and total deaths were higher in the asymptomatic hyperglycemic and known diabetics compared with low normal euglycemics.32 On the other hand, it is reported that intensive blood glucose control that significantly reduces HbA1C compared to conventional treatment does not reduce significantly the risk of diabetes-related death, all-cause mortality, and risk of MI.33 Hyperinsulinemia and hyperglycemia might affect patients through the comorbidities of hypertension, dyslipidemia, and central body fat distribution.34,35

The anthropometrical variables, as observed in the BMI values obtained, show excessive weight in most patients in all groups where BMI of control and patients were 31.05 ± 6.76, and 33.67 ± 6.02, respectively. These results are similar to those found in a multicenter study carried out with more than 2500 type II DM patients in 12 cities in different Brazilian regions.36 The high prevalence of overweight diabetic patients was observed by epidemiological research, which estimated that between 80% and 90% of individuals with type II DM are obese or overweight.36 The prevalence of obesity in diabetic patients is three times higher than in the population in general, highlighting the higher significant body mass index observed in our study.37

However, despite awareness about the importance of excessive body weight for morbidity and mortality of patients with type II DM, the control of this variable in diabetic populations has rarely been emphasized in most studies.36 In addition, the approach to this problem in basic health care has been neglected, since recommendations on the control of these variables exist in most services, but are not accompanied by resources that can adequately support individuals in an effective change that results in weight loss.

Laboratory data indicate high prevalence of dyslipidemia in the patients evaluated, similar to that found in a survey with type II DM patients performed in Rio Grande do Sul: 67% presented total cholesterol >200 mg/dL; 65% triglycerides >150 mg/dL, and 47% low HDL cholesterol >50 mg/dL.38 It is known that the two main components of diabetic dyslipidemia are the elevated levels of triglycerides and the low levels of HDL-cholesterol, both considered the main predictors of cardiovascular diseases.2

The mean values of triglycerides and LDL cholesterol observed in Figure 3 were above those recommended by the ADA.39 For diabetic patients, ADA recommends that HDL cholesterol values must be higher than 45 mg/dL; however, in this study, mean HDL was below this level (2.94 and 2.02 mmol/dL) in outpatient and intensive care unit diabetic subjects, respectively. This study also presented mean values of LDL-cholesterol above recommendations (133.66 mg/dL) in the patients evaluated, as LDL-cholesterol was 3.21 and 1.61 mmol/dL in outpatient diabetic subjects. These results are similar to the results of Carolino et al31 and Gomes et al,40 where the prevalence of dyslipidemia was (72.5%) in the patients evaluated. The mean values of triglycerides and LDL cholesterol were above those recommended by the ADA, as mean values of LDL-cholesterol above recommendations (133.66 mg/dL) in the patients evaluated.

Such lipid profiles, accompanied by the use of medication, strongly suggests inadequate diet and lack of physical activity. However, the need for better control of lipid levels has to be considered through a more effective and safe follow-up of the medications in use, which can even require dosage alteration.41

Regarding alteration in the lipid profile, the unfavorable impact of dyslipidemia on cardiovascular morbidity and mortality are largely acknowledged, as well as the frequent association of these conditions with diabetes.43 Moreover, a significant increase occurs in morbidity of individuals with types I and II DM in the presence of dyslipidemia. On the other hand, there is plenty of evidence that the treatment of dyslipidemia has a favorable effect on the control of macrovascular disease in diabetic individuals.39,44

The Framingham Study shows the relative impact of diabetes is substantially greater for women than for men. Nondiabetic women have lower relative CHD risk compared to nondiabetic men. The risk of cardiovascular mortality and morbidity was about as great for diabetic women as for diabetic men.44 Our study found the total risk among the diabetic patients was 2.57 (female main total risk was 5.195 ± 3.671 and the main total risk of the male patients was −0.60 ± 1.680). Also, the results of the present study are going with the results of Esteghamati et al,42 who studied the prevalence of cardiovascular risk factors in an Iranian population. Although it is suggested that the excess relative risk of CHD mortality in women versus men with diabetes might disappear after adjusting for classic CHD risk factors.46,47

In another study, which showed the high risk in females, the authors concluded that the sex difference was largely explained by the persistently more favorable survival rate of women.44

Conclusion

The risk predictors for CHD are high in diabetic patients and higher in diabetic females.