|Year : 2019 | Volume
| Issue : 3 | Page : 797-802
Pattern of coronary artery disease in high-risk patients without prior myocardial infraction
Hala M Badran1, Naglaa F Ahamed1, Abd Elmoaty G. Kishk2
1 Department of Cardiology, Menoufia University, Menoufia, Egypt
2 Department of Cardiology, Bulak ELdekrour General Hospital, Cairo, Egypt
|Date of Submission||13-Jan-2018|
|Date of Acceptance||17-Mar-2018|
|Date of Web Publication||17-Oct-2019|
Abd Elmoaty G. Kishk
Source of Support: None, Conflict of Interest: None
This study aimed to assess the causes, risk factors, outcome, and recommendation of patients with coronary artery disease without prior obstruction.
Materials and methods
Medline databases (PubMed, Circulation, American Society of Echocardiography, Journal of American Colleague of Cardiology, and ScienceDirect) and also materials available on the internet. The search was performed in the electronic databases from 2012 to 2017. The initial search presented 60 articles of which 23 met the inclusion criteria. The articles studied the pattern of coronary artery disease in patients with risk factors without prior obstruction. If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, adequate information, and defined assessment measures. Comparisons were made by a structured review with the results tabulated.
In total, 27 potentially relevant publications were included. The studies indicate that cardiovascular risk factors have a differential effect on women, and some risk factors are more common in women than in men.
Patients with angina and nonobstructive coronary angiograms are predominantly women, and many have a prognosis that is not as benign as commonly thought. Therapy should be directed at symptom relief; aggressive anti-ischemic medication should be applied when risk factors are present or when the prognostic risk is high.
Keywords: atherosclerosis, coronary angiography, coronary artery disease, prognosis, risk factors
|How to cite this article:|
Badran HM, Ahamed NF, G. Kishk AE. Pattern of coronary artery disease in high-risk patients without prior myocardial infraction. Menoufia Med J 2019;32:797-802
|How to cite this URL:|
Badran HM, Ahamed NF, G. Kishk AE. Pattern of coronary artery disease in high-risk patients without prior myocardial infraction. Menoufia Med J [serial online] 2019 [cited 2020 Apr 4];32:797-802. Available from: http://www.mmj.eg.net/text.asp?2019/32/3/797/268867
| Introduction|| |
Chest pain may be associated with coronary arteries that appear 'normal'. Normal is defined here as no visible disease or luminal irregularities (<50%) as judged visually at coronary angiography.
Normal angiography in patients with chest pain is five times more common in women than in men .
Among patients with chest pain and normal angiography, an unknown number are suffering from cardiac pain of ischemic origin. Uncertainty is often difficult to allay, for medical attendants as well as for patients, resulting in the perpetuation of symptoms, difficulties in management, and establishment of risk of subsequent coronary events .
Recognition of ischemic heart disease is often delayed or deferred in women. Consequently, many at risk for related adverse outcomes are not provided specific diagnostic, preventive, and/or treatment strategies. In part, this lack of recognition is related to sex-specific cardiovascular disease pathophysiology in women that differs from the traditional male-pattern model. The latter model is based largely upon studies where the majority of the participants were men with flow-limiting atherosclerotic coronary artery disease (CAD). Women are less likely to have flow-limiting obstructive CAD compared with men presenting with similar symptoms .
This nonobstructive CAD pattern and the tendency among women to have plaque erosion with subsequent thrombus formation, along with coronary microvascular disease, are not well recognized. Importantly, data are emerging to show that more extensive nonobstructive CAD involvement is associated with a rate of major adverse cardiovascular events that may approximate that of obstructive CAD. However, there are many limitations to our understanding of nonobstructive CAD, a consequence of numerous gaps in the current knowledge .
This study aimed to assess the causes, risk factors, outcome, and recommendation of patients with CAD without prior obstruction.
| Materials and Methods|| |
We reviewed papers on CAD, risk factors, normal or near-normal coronary angiography from mid-line database which are PubMed, Circulation, American Heart Association, Journal of American College of Cardiology, and ScienceDirect and also materials available on the internet. We used CAD, risk factors, normal or near-normal coronary angiography. The search was performed in the electronic databases from 2012 to 2017.
All the studies were independently assessed for inclusion. They were included if they fulfilled the following criteria.
Published in English language.
Published in peer-reviewed journals.
Focused on CAD in patients without prior obstruction and discusses the relation between risk factors and severity and outcome of coronary disease without prior obstruction.
If the studies did not fulfill the above criteria, they were excluded such as report without peer-review or not within national research program, letters/comments/editorials/news.
The analyzed publications were evaluated according to evidence-based medicine (EBM) criteria using the classification of the US Preventive Services Task Force and UK National Health Service protocol for EBM in addition to the evidence pyramid [Figure 1]. US Preventive Services Task Force format includes:
|Figure 1: Evidence pyramid. MA, meta-analysis; RCT, randomized controlled trial; SR, systematic review.|
Click here to view
- Level I: evidence obtained from at least one properly designed randomized, controlled trial
- Level II-1: evidence obtained from well-designed controlled trials without randomization
- Level II-2: evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group
- Level II-3: evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence
- Level III: opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
The quality of all the studies was assessed. Important factors included study design, attainment of ethical approval, evidence of power calculation, specified eligibility criteria, appropriate controls, adequate information, and specified assessment measures. It was expected that the confounding factors would be reported and controlled for and appropriate data analysis made in addition to an explanation of missing data.
A structured systematic review was performed with the results tabulated.
| Results|| |
Study selection and characteristics
In total, 60 potentially relevant publications were identified. Thirty-seven articles were excluded as they did not meet our inclusion criteria. A total of 23 studies were included in the review as they were deemed eligible by fulfilling the inclusion criteria. The majority of the studies evaluated the relationship between risk factors and both incidence and severity of CAD. Some studies examined the effect of drug therapy on CAD outcome. The studies were analyzed with respect to the study design using the classification of the US Preventive Services Task Force and UK National Health Service protocol for EBM.
Association atherosclerosis and coronary microvascular dysfunction on coronary artery disease
Two case–control studies , showed acute coronary syndromes (ACSs) often result from disruption of modestly stenotic plaques, not detectable by angiography, but only by intravascular ultrasound [Table 1].
|Table 1: Association of atherosclerosis and coronary microvascular dysfunction and nonobstructive coronary artery disease|
Click here to view
One case–control study  showed that coronary microvascular dysfunction has been documented among symptomatic women.
One cohort study  showed that atherosclerosis risk factors and coronary microvascular dysfunction with adverse outcome of nonobstructive CAD without flow-limiting coronary stenosis; one case–control study  showed among individuals with obstructive coronary.
Artery disease, noninvasive imaging has documented abnormal perfusion in myocardial regions supplied by vessels without apparent obstructive CAD.
Association of conventional risk factors and nonobstructive coronary artery disease
One case–control study  showed that depression is more common in women with myocardial infarction (MI) than in men. This sex-specific difference is particularly pronounced at young ages (<55 years; [Table 2]).
|Table 2: Association of conventional risk factors and nonobstructive coronary artery disease|
Click here to view
One case–control study  showed age-specific and sex-specific differences in baseline risk factors vary by age. Among the patients with ACS, women generally are older than men .
Hypertension women with ACS are more likely to have hypertension than men with ACS .
One case–control study  showed that smoking is a stronger risk factor for MI in women than in men. The risk difference is even greater in women aged less than 45 years.
One case–control study  showed that diabetes mellitus among patients with ACS and diabetes is more common in women than in men. The risk of MI and coronary heart disease is higher in women with diabetes than in men with diabetes.
One case–control study  showed obesity in patients with ACS, the prevalence of obesity is higher in young women (aged <55 years) than in men in the same age group.
One case–control study  showed that chronic kidney disease approximately is twofold more frequent in women than in men among patients with ST elevation MI.
Short-term and long-term prognosis in patients with ischemia without obstructive coronary artery disease
One case–control study  showed that the prognosis of 'normal' coronary arteries in the setting of signs and symptoms of myocardial ischemia is not as benign as reported. One case–control study  showed that short-term prognosis of patients with unstable angina and nonobstructive CAD includes a 2% risk of death or MI at 30 days of follow-up [Table 3].
|Table 3: Short-term and long-term prognosis in patients with ischemia without obstructive coronary artery disease|
Click here to view
One case–control study  showed women with nonobstructive coronary disease and evidence of myocardial ischemia have a relatively poor prognosis compared with women with nonobstructive coronary disease and no myocardial ischemia.
One case–control study  showed that patients with nonobstructive CAD are at increased risk for traditionally defined major cardiovascular events including premature death, MI, and stroke.
Management strategies in patients without obstructive coronary artery disease
One case–control study  showed that calcium antagonists not be used in patients with 'normal' angiograms because they seem to do little to prevent chest pain during daily life in these patients [Table 4].
|Table 4: Management strategies in patients without obstructive coronary artery disease|
Click here to view
One case–control study  showed β-blockers have been shown to be highly effective for reduction of chest pain episodes during daily life. There are several potential mechanisms by which β-blockers may act in reducing chest pain recurrences.
One case–control study  showed that statins and angiotensin-converting enzyme inhibitors improve endothelial dysfunction, may counteract oxidative stress, and may be of benefit in patients with 'normal' angiograms.
One case–control study  showed that clinical guidelines recommend managing all patients with ACSs with a standard set of therapies, independent of what coronary anatomy looks like.
| Discussion|| |
ACSs often result from disruption of modestly stenotic plaques, not detectable by angiography, but only by intravascular ultrasound ,. Plaque rupture and erosion often leads to thrombotic complications.
Coronary microvascular dysfunction has been documented among symptomatic women without flow-limiting coronary stenosis in the Women's Ischemia Syndrome Evaluation .
These studies have linked coronary microvascular dysfunction and atherosclerosis risk factors with adverse outcomes over follow-up coronary microvascular dysfunction have also been replicated in another female cohort .
Even among individuals with obstructive CAD, noninvasive imaging has documented abnormal perfusion in the myocardial regions supplied by vessels without apparent obstructive CAD .
Women with ACS have long been described as being 'older and sicker' than their male counterparts .
Smoking is a stronger risk factor for MI in women than in men (relative risk 3.3 vs. 1.9), and the difference in risk is even greater in women aged less than 45 years (relative risk 7.1 vs. 2.3) . Interestingly, smoking is the biggest risk factor for coronary plaque erosion, which is a particularly common mechanism of ACS in women. Less traditional comorbidities also affect the likelihood of women developing ACS in patients with ST elevation MI .
A seminal analysis of the GUSTO-IIb trial showed that women with ACS were older and had higher rates of traditional risk factors such as diabetes mellitus, hypertension ,,, and previous congestive heart failure compared with men with ACS differences in baseline risk factors seem to vary by age. A study from the US National Registry of Myocardial Infarction, a registry including greater than one million patients with MI between 1994 and 2006, showed that women aged less than 65 years were more likely to present with a history of diabetes, heart failure, or stroke, and with a higher Killip class than men in the same age group ,, These differences in presentation were less pronounced or absent altogether as patients aged. Several lifestyle and psychosocial factors also carry a differential risk of ACS in women and men, particularly in young women. Obesity is more common in young (aged <55 years) female patients with ACS than in their male counterparts (prevalence 51 vs. 45%) , although this difference does not seem to exist in older women  chronic kidney disease is approximately twofold more frequent in women than in men, and is associated with worse outcomes .
The prognosis of 'normal' coronary arteries in the setting of signs and symptoms of myocardial ischemia is not as benign as reported by preliminary cohort studies .
Short-term prognosis of patients with unstable angina and nonobstructive CAD includes a 2% risk of death or MI at 30 days of follow-up .
Most recently, outcome data from the National Heart, Lung, and Blood Institute-sponsored the Women's Ischemia Syndrome Evaluation study documents that women with nonobstructive coronary disease and evidence of myocardial ischemia have a relatively poor prognosis compared with women with nonobstructive coronary disease and no myocardial ischemia .
These patients are at increased risk for traditionally defined major cardiovascular events including premature death, MI, and stroke .
Observational evidence does not support the widespread use of calcium antagonists in patients with 'normal' angiograms because they seem to do little to prevent chest pain during daily life in these patients . Other work has documented that calcium antagonists fail to ameliorate the diminished coronary blood flow reserve of these patients .
β-Blockers have been shown to be highly effective for the reduction of chest pain episodes during daily life . There are several potential mechanisms by which β-blockers may act in reducing chest pain recurrences. They may counteract the proischemic effects of increased adrenergic tone or may simply reduce myocardial oxygen demand. β-Blockers are endothelium-dependent vasodilators as well. The proven benefit of exercise training in this population suggests that the mechanism of adrenergic modulation plays a role .
Statins and angiotensin-converting enzyme inhibitors improve endothelial dysfunction and may counteract oxidative stress, and may be of benefit in patients with 'normal' angiograms. The beneficial effects of statins on coronary microcirculation have been documented in other clinical studies .
The authors recommend managing all patients with ACSs with a standard set of therapies, independent of what coronary anatomy looks like .
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sullivan AK, Holdright DR, Wright CA, Sparrow JL, Cunningham D, Fox KM. Chest pain in Sparrow women: clinical, investigative, and prognostic features. BMJ 1994; 308
Bugiardini R, Bairey Merz CN. Angina with 'normal' coronary arteries: a changing philosophy. JAMA 2005; 293
Jespersen L, Hvelplund A, Abildstrøm SZ, Pedersen F, Galatius S, Madsen JK, et al
. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J 2012; 33
Bittencourt MS, Hulten E, Ghoshhajra B, O'Leary D, Christman MP, Montana P, et al
. Prognostic value of no obstructive and obstructive coronary artery disease detected by coronary computed tomography angiography to identify cardiovascular events. Circ Cardiovasc Imaging 2014; 7
Lin FY, Shaw LJ, Dunning AM, LaBounty TM, Choi JH, Weinsaft JW, et al
. Mortality risk in symptomatic patients with no obstructive coronary artery disease: a prospective 2-center study of 2,583 patients undergoing 64-detector row coronary computed tomographic angiography J Am Coll Cardiol 2011; 58
Shah S, Bellam N, Leipsic J, Berman DS, Quyyumi A, Hausleiter J, et al
. CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) Investigators. Prognostic significance of calcified plaque among symptomatic patients with nonobstructive coronary artery disease. J Nucl Cardiol 2014; 21
Pepine CJ, Anderson RD, Sharaf BL, Reis SE, Smith KM, Handberg EM, et al
. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia: results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. J Am Coll Cardiol 2010; 55
Agarwal M, Shufelt C, Mehta PK, Gill E, Berman DS, Li D, et al
. Cardiac risk factors and myocardial perfusion reserve in women with microvascular coronary dysfunction. J Am Coll Cardiol 2013; 3
Uren NG, Marraccini P, Gistri R, de Silva R, Camici PG. Altered coronary vasodilator reserve and metabolism in myocardium subtended by normal arteries in patients with coronary artery disease. J Am Coll Cardiol 1993; 22
Smolderen KG, Strait KM, Dreyer RP, D'Onofrio G, Zhou S, Lichtman JH, et al
. Depressive symptoms in younger women and men with acute myocardial infarction: insights from the VIRGO study. J Am Heart Assoc 2015; 4
Hochman JS, Tamis JE, Thompson TD. Sex, clinical presentation, and outcome in patients with acute coronary syndromes. J Vasc Interv Radiol 2000; 341
Njølstad I, Arnesen E, Lund-Larsen PG. Smoking, serum lipids, blood pressure, and sex differences in myocardial infarction. A 12-year follow-up of the Finnmark study. Circulation 1996; 93
Kappert K, Böhm M, Schmieder R, Schumacher H, Teo K, Yusuf S, et al.
Impact of sex on cardiovascular outcome in patients at high cardiovascular risk: analysis of the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects With Cardiovascular Disease (TRANSCEND) and the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET). Circulation 2012; 126
Pelletier R, Khan NA, Cox J, Daskalopoulou SS, Eisenberg MJ, Bacon SL, et al.
Gender differences in pre-event health status of young patients with acute myocardial infarction: a VIRGO study analysis. Eur Heart J Acute Cardiovasc Care 2016; 5
Lawesson SS, Alfredsson J, Szummer K, Fredrikson M, Swahn E. Prevalence and prognostic impact of chronic kidney disease in STEMI from a gender perspective: data from the SWEDEHEART register, a large Swedish prospective cohort. BMJ 2015; 5
Lichtlen PR, Bargheer K, Wenzlaff P. Long-term prognosis of patients with anginalike chest pain andnormal coronary angiographic findings. J Am Coll Cardiol 1995; 25
Diver DJ, Bier JD, Ferreira PE, Sharaf BL, McCabe C, Thompson B, et al
. Clinical and arteriographic characterization of patients with unstableangina without critical coronary arterial narrowing (from the TIMI-IIIA trial). Am J Cardiol 1994; 74
Johnson BD, Shaw LJ, Buchthal SD. Prognosis in women with myocardial ischemia in the absence of obstructive coronary disease: results from the National Institutes of Health-National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). Circulation 2004; 109
Halcox JP, Schenke WH, Zalos G, Mincemoyer R, Prasad A, Waclawiw MA, et al
. Prognostic value of coronary vascular endothelial dysfunction. Circulation 2002; 106
Masumoto A, Mohri M, Takeshita A. Three-year follow-up of the Japanese patients with microvascular angina attributable to coronary microvascular spasm. Int J Cardiol 2001; 81
Lanza GA, Colonna G, Pasceri V, Maseri A. Atenolol versus amlodipine versus isosorbide-5-mononitrate on anginal symptoms in syndrome X. Am J Cardiol 1999; 84
Kayikcioglu M, Payzin S, Yavuzgil O, KultursayH, Can LH, Soydan I. Benefits of statin treatment incardiac syndrome-X1. Eur Heart J 2003; 24
Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, et al
. American College of Cardiology; American Heart Association. Committee on the Managementof Patients with Unstable Angina. ACC/AHA2002 guideline update for the managementof patients with unstable angina and non-STsegmentelevation myocardial infarction – summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol 2002; 40
[Table 1], [Table 2], [Table 3], [Table 4]