Atypical presentation of acute and chronic coronary artery disease in diabetics

Table 1 Studies on silent myocardial ischemia as a mode of atypical presentation in diabetics

Ref.	Study population	Study type/country	Silent ischemia%	Conclusion
Arenja et al[36]	1621 pts in the derivation cohort + 338 pts in the validation cohort	Derivation cohort/ Switzerland	23.3%- 28.5% in DM and 21.5% in non-DM	DM is an independent predictor for the presence of SMI (OR = 1.5; 95%CI: 1.1-1.9, P = 0.004). In the validation cohort, the prevalence of SMI = 26.3% (n = 89), while the prevalencea in diabetics (35.8%) vs non-diabetics was 24% (P = 0.049)
Sheikh et al[37]	200 subjects, 31 diabetics vs 169 non-diabetics	A cross-sectional study/Pakistan	(19%) diabetics vs (13%) non-diabetics	No significant difference in the frequency of SMI in diabetics vs non-diabetics
Peña et al[38]	220 asymptomatic NIDDM patients	A prospective, observational, analytical study /Havana	29.10%	Type 2 diabetics with ischemia had ↑ levels of total cholesterol, LDL and triglycerides. HDL levels were significantly reducedb. The association of ↓ HDL with ↑ triglycerides was a strong indicator of SMI in NIDDM patients
Ruano Pérez et al[39]	56 asymptomatic diabetics	retrospective study	46.40%	Moderate-severe ischemia in 10.7%, necrosis with ischemia in 5.4% and necrosis in 7.1%, diabetic nephropathy was the only factor related to an abnormal SPECT (P = 0.043)
Blanchet Deverly et al[40]	147 NIDDM patients	cross-sectional study /France	23.10%	Multivariate logistic-regression analyses, the adjusted OR of SMI significantly ↑ in patients with a history of cardiovascular disease (4.36, 95%CI: 1.36-13.96, P = 0.01) and LVH (2.46, 95%CI: 1.03-5.86, P = 0.04)
Mbaye et al[41]	79 diabetics	Prospective/France	67.10%	Predominance of motion abnormalities in the anterior territory (83%). Cardiovascular risk factors associated with positivity of the test were microalbuminuria (P = 0.0001), inactivity (P = 0.0001), dyslipidemia (P = 0.0002), arterial hypertension (P = 0.001), smoking (0.003) and male sex (P = 0.004)
Bansal et al42]	1123 NIDDM patients	Prospective/Detection of Ischemia in Asymptomatic Diabetics ( DIAD) /United States and Canada (DIAD) study	21%-24% in the intermediate high risk group 19%-23% in the low risk group	Cardiac event ratesa in intermediate/high-risk. The annual cardiac event rate was ≤ 1% in all risk groups. In intermediate-/high-risk participants randomized to screening vs no screening, 4.8-yr cardiac event rates were similar (2.5%-4.8% vs 3.1%-3.7%)
Agarwal et al[43]	77 NIDDM	Prospective study/India	28.90%	The prevalence of SMI similar in males and females. Serum LDL levels > 140 mg % had a significant correlation with the prevalence of silent CAD (P = 0.04). The difference in CCA-IMT values was found to be statistically significant between the silent CAD and non-CAD groups (P = 0.019)
Ugur-Altun et al[44]	90 asymptomatic NIDDM patients	Prospective/Turkey	4%	Diabetics with SMI had ↑ fibrinogen level (372 ± 51 mg/dL vs 307 ± 71 mg/dL, P = 0.04), had b total exercise time and peak workload (375 ± 30 s vs 474 ± 115 s, P = 0.04; 7.3 ± 0.5 vs 8.9 ± 1.9, P = 0.04, respectively)
Chico et al[47]	353 NIDDM asymptomatic Caucasians	Prospective/Spain	8.50%	SMI patients were older, had ↑ prevalence of autonomic neuropathy, microalbuminuria, hypertension, and dyslipidemia than those without
Wackers et al[48]	1123 NIDDM patients	Prospective/United States	20%	Predictors for abnormal tests: abnormal Valsalva, male sex and diabetes duration (5.2). Traditional cardiac risk factors or inflammatory and prothrombotic markers were not predictive. Ischemic adenosine-induced ST-segment depression with normal perfusion in women
Falcone et al[50]	618 patients with CAD	Prospective/Italy	58%	SMI during exercise seen in 58% of diabetics and 64% of nondiabetics. Both diabetics and non-diabetics with exertional SMI had ↑ heart rate values (P < 0.01), SBP (P < 0.01), rate-pressure product (P < 0.001), work load (P < 0.01) and maximum ST depression at peak exercise (P < 0.05)
Coisne et al [51]	49 diabetics and 63 non-diabetics	Prospective/France	9%	Significant CAD detected in 9% of asymptomatic diabetics. Dynamic left ventricular obstruction observed in 59% of the diabetic population and in only 22% in the non-diabetic population
Sukhija et al[53]	30 diabetics/30 non diabetics	Prospective/India	46.70%	Diabetics had ↑ heart rate and a greater number of supraventricular and ventricular ectopics, aprevalence of multi-vessel involvement and diffuse disease compared to controls. 50% of diabetics and none of the controls had autonomic dysfunction. Autonomic dysfunction was present in 85.7% of diabetics with SMI vs 18.7% of diabetics without SMI (P = 0.001)
May et al[54]	240 diabetics	Prospective/Denmark	13.50%	Frequency of SMI did not differ significantly between diabetics and non-diabetics. Systolic blood pressure was predictive of SMI in diabetes
Tamez-Pérez et al[55]	60 NIDDM patients	Prospective/ Spain	17%	In a 2-yr follow-up, 4 diabetics developed symptomatic angina pectoris
Ahluwalia et al[56]	20 male diabetics	Prospective/India	50%	On exercise testing in diabetics, SMI was detected in 64% of the patients with 3 vessel disease, 50% of the patients with 2 vessel disease and 20% of the patients with one-vessel disease vs 18% of non-diabetic patients with three-vessel disease (P < 0.05) and in none of the patients with two- or one-vessel disease
Tanaka et al[61]	92 NIDDM patients	Prospective / Japan	38%	Diabetics with positive treadmill test were smokers, and had hypertension and ↑ triglyceride level compared to treadmill negative diabetics
Nesto et al[62]	30 diabetics with peripheral vascular disease	Prospective /United States	57%	57% had thallium abnormalities, with reversible thallium defects compatible with ischemia in 47% and evidence of prior, clinical SMI in 37%. Thallium abnormalities were seen more frequently in diabetics with concomitant hypertension and cigarette smoking (P = 0.001)
Koistinen et al[63]	136 diabetic subjects	Controlled study/ Finland	29%	Coronary angiography of 34 diabetics; 12 had significant coronary artery narrowing; seven had unimportant atherosclerosis; 15 had patent coronary arteries
Theron et al[64]	52 IDDM and 87 NIDDM subjects	Prospective /South Africa	See conclusion	No statistically significant relationship between any parameter and the presence of autonomic neuropathy. Atypical infarctions not limited to subjects with autonomic neuropathy, the incidence mucha than the general population
Touze et al[65]	50 black African diabetics	Prospective /Africa	10%	SMI was ↓ among black African diabetics compared with white diabetics. The coronary lesions were mostly limited. Proximal narrowing and one-vessel disease mostly encountered-

^aIncrease/higher;

^bDecreased/lower. CAD: Coronary artery disease; IDDM: Insulin dependent diabetes mellitus; NIDDM: Non-insulin dependent diabetes mellitus; MI: Myocardial infarction; HDL: High density lipoprotein; LDL: Low density lipoprotein; SMI: Silent myocardial ischemia/infarction; CCA-IMT: Common carotid artery intimal medial thickness

Table 2 Studies which have shown that diabetes mellitus is a predictor of atypical presentation of acute coronary syndrome

Ref.	Study population/	Study type/country	Atypical presentation %	Conclusion
Stern et al[68]	2113 ACS patients	Nationwide survey/Israel	21.7% had no chest pain	In multivariate analysis, variables associated with no anginal pain/atypical symptoms on presentation (ina order): history of heart failure, age, no past angina, diabetes and non-smoking. 18.7% of male patients had no chest pain on presentation vs 29.7% of females
Culić et al[69]	1996 MI patients	A prospective, observational study/Croatia	14.8% had no chest pain	The independent predictors of atypical presentation in both gender; alevels of CK-MB fraction (P < 0.0001 and P = 0.0003, respectively), NIDDM (P = 0.0002 and P = 0.002, respectively), older age (P = 0.001 and P = 0.01, respectively), and no smoking in men (P = 0.005) The independent predictors of the presence of non-pain symptoms; DM (P = 0.048 and P = 0.005, respectively), alevels of CK-MB (P = 0.01 and P = 0.049, respectively) and hypercholesterolemia (P =0.01) in both men and women
Hwang et al[70]	931 newly diagnosed as ACS	Retrospective/ South Korea	7.8% of younger pts and 13.4% of older pts	A logistic regression analysis after adjustment for gender and ACS type indicated that diabetes and hyperlipidemia significantly predicted atypical symptoms in younger patients
MacKenzie et al[71]	64 (12 women with DM)	Descriptive, cross-sectional/Canada	See conclusion	Less chest pain in diabetics vs non-diabetics (P = 0.02) No difference in pain intensity in diabetics with MI vs non-diabetics (P≥ 0.05) Diabetics with UA or MI were more likely to report mid-sternal chest pain (P = 0.04) and chest pain that radiated to the back of the left arm (P = 0.01) than non-diabetics Diabetics with UA or MI reported more SOB (53.1% vs 31.3%; NS) In diabetics with UA or MI, SOB was a factor in deciding to seek care
Coronado et al[72]	2541 (1058 women, 410 women with DM);	Secondary analysis of multisite a prospective clinical trial/United States	6.2% of patients with ACS and in 9.8% of AMI.	DM independent predictor of painless presentation in acute MI, but not in the ACS group. Diabetes more common in non-pain ACS (35% vs 26%; P = 0.01) Shortness of breath most common in the painless presentation group (72%) and women were more likely to have painless ACS (53%) (P = 0.007)
Vaccarino et al[73]	384878 patients	Prospective, observational study/ National Registry of MI/United States	33%	Atypical presentation patient: older, ↑ proportion of women and diabetics without a significant interaction between sex and diabetes (P = 0.30). HF comorbidities and less likely to have coronary intervention with bchance of anticoagulants, aspirin and β blocker usage
Canto et al[74]	434877 MI ptsJune 1994-March 1998	Prospective observational study United States	33% had no chest pain	Patients without chest pain on presentation: Likely to be diabetics (32.6% vs 25. 4%) Older (74.2 yr vs 66.9 yr). Likely to be female (49.0% vs 38.0%) Likely to have prior HF (26.4% vs 12.3%)Had a longer delay before hospital presentation (mean, 7.9 h vs 5.3 h) Less likely to be diagnosed with confirmed MI at the time of admission (22.2% vs 50.3%) Less likely to receive thrombolysis or PCI (25.3% vs 74.0%), aspirin (60.4% vs 84.5%), BB (28.0% vs 48.0%), or heparin (53.4% vs 83.2%). 23.3% in-hospital mortality vs 9.3% in patients with chest pain
Medalie et al[75]	9509 healthy adult subjects	Israeli Heart Attack study, cohort/ Israel	3.6 unrecognized MI/ 1000 persons and 5.3 clinical MI/1000 persons	By multivariate analysis, age, left axis deviation, LVH, cigarette smoking, systolic or diastolic BP, and PVD were the most significant risk factors. Cholesterol, DM, anxiety, and psychosocial problems, do not play a significant role in unrecognized MI
Brieger et al[76]	20881 ACS patients	Global Registry of Acute Coronary Events/multinational, prospective, observational study (in 14 countries)	8.4% presented without chest pain	23.8% not initially recognized as having an ACS, < 33% of the population with atypical symptoms were diabetics. Less likely to receive effective cardiac medications ahospital morbidity and mortality (13% vs 4.3%, respectively; P < 0.0001) ahospital mortality rates in patients with presenting symptoms of pre-syncope/syncope. Nausea or vomiting, dyspnea and in those with painless presentations of UA

^aIncrease/higher;

^bDecreased/lower. MI: Myocardial infarction; UA: Unstable angina; AMI: Acute myocardial infarction; ACS: Acute coronary syndrome; DM: Diabetes mellitus; SOB: Shortness of breath.

Table 3 Studies which have not shown that diabetes mellitus is a predictor of atypical presentation of acute coronary syndrome

Ref.	Study population/	Study type/country	Atypical presentation %	Conclusion
Meshack et al[77]	589 patients, aged 25 to 74 yr, with AMI	A community-based surveillance program/ United States	Sweating (64.2%), fatigue (62.6%), dyspnea (60.3%), and arm or jaw pain (58.2%).	Adjusting for age, DM, gender, and relative to non-Hispanic whites, Mexican Americans were more likely to report chest pain, upper back pain, and palpitations, and less likely to report arm or jaw pain
Richman et al[78]	216 (19 women with DM); AMI	A prospective, observational study/United States	No statistical difference in diabetics vs non-diabetics in terms of the presence chest pain	No difference in the frequency of chest pain or associated symptoms by diabetic status (P≥ 0.05) -no chest pain symptoms was more common in diabetic patients (NS)
Kentsch et al[79]	1042 (330 women; 155 women with DM) with STEMI	Secondary analysis of MITRA PLUS (18786 pts.; North German Registry, NGR, 1042 pts.)/ Germany	16.9% of DM and 15.0% of non-DM	No difference in the frequency or intensity of chest pain by diabetic status Patients with DM reported significantly more dyspnea than those without DM (29.5% vs 19.5%; P < 0.01)
DeVon et al[80]	100 (50 women, 23 women with DM); DM	rospective secondary analysis; descriptive, cross-sectional; structured interview/United States	3%	No difference in the frequency and severity of chest pain in diabetics vs non-diabetics (P ≥ 0.05) No differences in UA symptoms by diabetic status Patients with DM reported weakness as the second most common symptom and more likely to describe chest pain as squeezing (P = 0.02) or aching (P = 0.04) than non-diabetics Diabetics had ↑ frequency of hyperventilation (P = 0.04) and afrequency of nausea (P = 0.04) than non-diabetics
Thuresson et al[81]	N = 1939 (480 women, 82 women with DM)	Descriptive, cross-sectional study/Sweden	See conclusion	No difference in chest pain or other ACS symptoms by DM status Women reported more tiredness/weakness, anxiety/fear, vomiting, back pain, left arm pain and neck or jaw pain than men (P = 0.01).

^aDecreased/lower. STEMI: ST elevation myocardial infarction; UA: Unstable angina AMI: Acute myocardial infarction; ACS: Acute coronary syndrome; DM: Diabetes mellitus; PVD: Peripheral vascular disease.