Coronary Heart Disease
How Long do Your Angiographically Normal Coronary Arteries Remain Normal? A Pilot Study
Angiology 2015, Vol. 66(3) 262-264 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714531646 ang.sagepub.com
Jean Marc Weinstein, MB, BS, FRCP1, Carlos Cafri, MD1, Sergio Kobal, MD1, Michael Sherf, MD, MPH1, and Reuben Ilia, MD1
Abstract Coronary atherosclerosis is a progressive disease. We sought to determine whether this fact also applies to patients at an advanced age with normal coronary arteries (NCAs) undergoing repeat catheterization at least 5 years later. Of the 189 patients who were found to have NCAs, 154 (81%) remained with NCAs and 35 (19%) developed obstructive coronary artery disease (OCAD). Development of OCAD was observed at all ages. Isolated risk factors were not associated with the appearance of OCAD, but the combination of diabetes mellitus with age >65 years or with smoking was associated with the appearance of OCAD (P ¼ .04 for both). In conclusion, the finding of angiographically NCAs in elderly individuals does not prevent the later development of OCAD. Keywords normal coronary arteries, atherosclerosis, progression, risk factors
Introduction Coronary atherosclerosis is a progressive disease and even in its mild forms of expression as nonobstructive disease, it may further deteriorate. Angiographically normal coronary arteries (NCAs) are not infrequently found during cardiac catheterization.1-4 It may be assumed that if NCAs are found at a relatively advanced age, the chances of developing obstructive atheroma are very low. We sought to determine whether this assumption is true and whether other risk factors for atherosclerosis interact with age in the development of coronary disease.
Methods We performed a pilot study, retrospectively analyzing all patients who underwent 2 coronary angiography studies at our institution at least 5 years apart between 1996 and 2013, who had angiographically NCAs at the first study. Data collected included age at first and second catheterization, gender, presence of coronary risk factors, indication for catheterization, and the angiographic findings at the second catheterization regarding the appearance of obstructive coronary artery disease (OCAD, defined as stenosis 50%). The results of the second catheterization were also analyzed according to age groups.
Statistics Continuous variables were analyzed with independent samples 2-tailed t-test. Categorical variables were analyzed using
the chi-square test. A P < .05 was defined as significant. The statistical analysis was performed using SPSS software (version 18, SPSS Inc, Chicago, Illinois).
Results Of the 43 351 patients catheterized during this period, 189 patients who were found to have NCAs at their initial catheterization underwent an additional catheterization study at least 5 years after the first. The second catheterization was performed 9 + 3 years after the first. Of these patients, 154 (81%) remained with NCAs and 35(19%) developed OCAD. There was no difference in regard to the time interval between the 2 catheterizations in the groups. There were no significant differences between the 2 groups regarding age, gender, and individual risk factors for the development of atherosclerosis (Table 1). When looking at combinations of 2 risk factors regarding the development of OCAD using univariate analysis, only the combination of diabetes with smoking or diabetes with age >65 years was found to be significantly associated with the development of 1
Cardiology Department, Soroka Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel
Corresponding Author: Reuben Ilia, Cardiology Department, Soroka University Medical Center, BeerSheva, Israel. Email: [email protected]
Downloaded from ang.sagepub.com at UNIV OF PITTSBURGH on March 14, 2015
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Table 1. Demographic and Clinical Characteristics of Patients on Second Coronary Angiography at least 5 Years After the First Among 189 Patients With Initially Angiographically Normal Coronary Arteries.
Mean follow-up, years Age, years Male, % Diabetes mellitus, % Hypertension, % Dyslipidaemia, % Smoking, % Reason for second cath, % Stable angina ACS/STEMI Valve disease Chest pain
NCAs (n ¼ 154)
OCAD (n ¼ 35)
P
9+3 62 + 9 53 22 56 90 39
8+3 63 + 11 63 33 64 93 50
NS NS NS NS NS NS NS
20 33 19 28
24 42 16 18
NS
Abbreviations: NCAs, normal coronary arteries, OCAD, obstructive coronary artery disease, cath, catheterization, ACS/STEMI, acute coronary syndrome/ ST-segment elevation myocardial infarction; NS, not significant.
OCAD (18% vs 7% and 32% vs 16%, respectively; P ¼ .04 for both combinations). We further analyzed the appearance of OCAD in different age groups (70 years) and found no differences in any of the age groups (38% vs 40%, 57% vs 57%, and 5% vs 3%, respectively).
Discussion Coronary atherosclerosis is a progressive disease as demonstrated at repeat catheterizations. Despite this knowledge, there may be a ‘‘gut feeling’’ among cardiologists that if a patient is found to have NCAs when catheterized at an advanced age, the chances of developing OCAD are very low. Therefore, when such a patient presents with a suspected coronary syndrome, the threshold to recommend repeat catheterization is often high. It should be remembered, however, that the demonstration of angiographically NCAs does not exclude the presence of atheroma,5 which is the precursor of OCAD. Often minimal plaques are unnoticed on angiography, and plaque rupture may lead to healing with progression to obstruction. There is a paucity of data in the literature regarding angiographic follow-up of patients with apparently NCAs. Marchandise et al6 described such a series but with a very small number of patients (n ¼ 22 with NCAs) who were also considerably younger (mean age 49 years) than our study population and with a much shorter period of follow-up (< 4 years mean follow-up). In contrast to our findings, no progression was demonstrated in their patients, presumably due to the aforementioned differences. We have no precise data regarding risk factor management in the population studied, but the fact that OCAD developed in patients with NCAs even at an advanced age emphasizes the need for appropriate treatment. Thus, we believe that elderly patients with NCAs on catheterization should have risk factor management as in the general population, although this approach is not strongly supported by the recent American College of
Cardiology/American Heart Association Blood Cholesterol Guideline.7
Limitations This is a retrospective analysis. The assessment of the presence or absence of NCAs was on the basis of visual analysis alone, and no advanced methods were utilized to confirm the findings. In the group of patients who went on to develop OCAD, there was a slightly higher frequency of atherosclerotic risk factors, although there were no statistically significant differences between the groups, probably due to the small number of patients included. This observation has encouraged us to extend the study to a larger population with a longer follow-up. Our study found that the age at which the coronary arteries were found to be normal on catheterization has no relationship with the future development of OCAD. The decision to recatheterize should be based on clinical judgment. 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.
References 1. Bradley SM, Maddox TM, Stanislawski MA, et al. Normal coronary rates for elective angiography in the VA health care system: insights from the VA CART program. J Am Coll Cardiol. 2014; 63(5):417-426. 2. Kemp HG, Kronmal RA, Vlietstra RE, Frye RL. Seven year survival of patients with normal or near normal coronary arteriograms: a CASS registry study. J Am Coll Cardiol. 1986;7(3): 479-483.
Downloaded from ang.sagepub.com at UNIV OF PITTSBURGH on March 14, 2015
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Angiology 66(3)
3. Douglas PS, Patel MR, Bailey SR, et al. Hospital variability in the rate of finding obstructive coronary artery disease at elective, diagnostic coronary angiography. J Am Coll Cardiol. 2011;58(8):801-809. 4. Levitt K, Guo H, Wijeysundera HC, et al. Predictors of normal coronary arteries at coronary angiography. Am Heart J. 2013; 166(4):694-700. 5. Mintz GS, Painter JA, Pichard AD, et al. Atherosclerosis in angiographically ‘‘normal’’ coronary artery reference segments: an intravascular ultrasound study with clinical correlations. J Am Coll Cardiol. 1995;25(7):1479-1485.
6. Marchandise B, Bourassa MG, Chaitman BR, Lesperance J. Angiographic evaluation of the natural history of normal coronary arteries and mild coronary atherosclerosis. Am J Cardiol. 1978;41(2):216-220. 7. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines. J Am Coll Cardiol. 2014;63(25 Pt B): 2889-2934.
Downloaded from ang.sagepub.com at UNIV OF PITTSBURGH on March 14, 2015
How Long do Your Angiographically Normal Coronary Arteries Remain Normal? A Pilot Study
Angiology 2015, Vol. 66(3) 262-264 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714531646 ang.sagepub.com
Jean Marc Weinstein, MB, BS, FRCP1, Carlos Cafri, MD1, Sergio Kobal, MD1, Michael Sherf, MD, MPH1, and Reuben Ilia, MD1
Abstract Coronary atherosclerosis is a progressive disease. We sought to determine whether this fact also applies to patients at an advanced age with normal coronary arteries (NCAs) undergoing repeat catheterization at least 5 years later. Of the 189 patients who were found to have NCAs, 154 (81%) remained with NCAs and 35 (19%) developed obstructive coronary artery disease (OCAD). Development of OCAD was observed at all ages. Isolated risk factors were not associated with the appearance of OCAD, but the combination of diabetes mellitus with age >65 years or with smoking was associated with the appearance of OCAD (P ¼ .04 for both). In conclusion, the finding of angiographically NCAs in elderly individuals does not prevent the later development of OCAD. Keywords normal coronary arteries, atherosclerosis, progression, risk factors
Introduction Coronary atherosclerosis is a progressive disease and even in its mild forms of expression as nonobstructive disease, it may further deteriorate. Angiographically normal coronary arteries (NCAs) are not infrequently found during cardiac catheterization.1-4 It may be assumed that if NCAs are found at a relatively advanced age, the chances of developing obstructive atheroma are very low. We sought to determine whether this assumption is true and whether other risk factors for atherosclerosis interact with age in the development of coronary disease.
Methods We performed a pilot study, retrospectively analyzing all patients who underwent 2 coronary angiography studies at our institution at least 5 years apart between 1996 and 2013, who had angiographically NCAs at the first study. Data collected included age at first and second catheterization, gender, presence of coronary risk factors, indication for catheterization, and the angiographic findings at the second catheterization regarding the appearance of obstructive coronary artery disease (OCAD, defined as stenosis 50%). The results of the second catheterization were also analyzed according to age groups.
Statistics Continuous variables were analyzed with independent samples 2-tailed t-test. Categorical variables were analyzed using
the chi-square test. A P < .05 was defined as significant. The statistical analysis was performed using SPSS software (version 18, SPSS Inc, Chicago, Illinois).
Results Of the 43 351 patients catheterized during this period, 189 patients who were found to have NCAs at their initial catheterization underwent an additional catheterization study at least 5 years after the first. The second catheterization was performed 9 + 3 years after the first. Of these patients, 154 (81%) remained with NCAs and 35(19%) developed OCAD. There was no difference in regard to the time interval between the 2 catheterizations in the groups. There were no significant differences between the 2 groups regarding age, gender, and individual risk factors for the development of atherosclerosis (Table 1). When looking at combinations of 2 risk factors regarding the development of OCAD using univariate analysis, only the combination of diabetes with smoking or diabetes with age >65 years was found to be significantly associated with the development of 1
Cardiology Department, Soroka Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel
Corresponding Author: Reuben Ilia, Cardiology Department, Soroka University Medical Center, BeerSheva, Israel. Email: [email protected]
Downloaded from ang.sagepub.com at UNIV OF PITTSBURGH on March 14, 2015
Weinstein et al
263
Table 1. Demographic and Clinical Characteristics of Patients on Second Coronary Angiography at least 5 Years After the First Among 189 Patients With Initially Angiographically Normal Coronary Arteries.
Mean follow-up, years Age, years Male, % Diabetes mellitus, % Hypertension, % Dyslipidaemia, % Smoking, % Reason for second cath, % Stable angina ACS/STEMI Valve disease Chest pain
NCAs (n ¼ 154)
OCAD (n ¼ 35)
P
9+3 62 + 9 53 22 56 90 39
8+3 63 + 11 63 33 64 93 50
NS NS NS NS NS NS NS
20 33 19 28
24 42 16 18
NS
Abbreviations: NCAs, normal coronary arteries, OCAD, obstructive coronary artery disease, cath, catheterization, ACS/STEMI, acute coronary syndrome/ ST-segment elevation myocardial infarction; NS, not significant.
OCAD (18% vs 7% and 32% vs 16%, respectively; P ¼ .04 for both combinations). We further analyzed the appearance of OCAD in different age groups (70 years) and found no differences in any of the age groups (38% vs 40%, 57% vs 57%, and 5% vs 3%, respectively).
Discussion Coronary atherosclerosis is a progressive disease as demonstrated at repeat catheterizations. Despite this knowledge, there may be a ‘‘gut feeling’’ among cardiologists that if a patient is found to have NCAs when catheterized at an advanced age, the chances of developing OCAD are very low. Therefore, when such a patient presents with a suspected coronary syndrome, the threshold to recommend repeat catheterization is often high. It should be remembered, however, that the demonstration of angiographically NCAs does not exclude the presence of atheroma,5 which is the precursor of OCAD. Often minimal plaques are unnoticed on angiography, and plaque rupture may lead to healing with progression to obstruction. There is a paucity of data in the literature regarding angiographic follow-up of patients with apparently NCAs. Marchandise et al6 described such a series but with a very small number of patients (n ¼ 22 with NCAs) who were also considerably younger (mean age 49 years) than our study population and with a much shorter period of follow-up (< 4 years mean follow-up). In contrast to our findings, no progression was demonstrated in their patients, presumably due to the aforementioned differences. We have no precise data regarding risk factor management in the population studied, but the fact that OCAD developed in patients with NCAs even at an advanced age emphasizes the need for appropriate treatment. Thus, we believe that elderly patients with NCAs on catheterization should have risk factor management as in the general population, although this approach is not strongly supported by the recent American College of
Cardiology/American Heart Association Blood Cholesterol Guideline.7
Limitations This is a retrospective analysis. The assessment of the presence or absence of NCAs was on the basis of visual analysis alone, and no advanced methods were utilized to confirm the findings. In the group of patients who went on to develop OCAD, there was a slightly higher frequency of atherosclerotic risk factors, although there were no statistically significant differences between the groups, probably due to the small number of patients included. This observation has encouraged us to extend the study to a larger population with a longer follow-up. Our study found that the age at which the coronary arteries were found to be normal on catheterization has no relationship with the future development of OCAD. The decision to recatheterize should be based on clinical judgment. 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.
References 1. Bradley SM, Maddox TM, Stanislawski MA, et al. Normal coronary rates for elective angiography in the VA health care system: insights from the VA CART program. J Am Coll Cardiol. 2014; 63(5):417-426. 2. Kemp HG, Kronmal RA, Vlietstra RE, Frye RL. Seven year survival of patients with normal or near normal coronary arteriograms: a CASS registry study. J Am Coll Cardiol. 1986;7(3): 479-483.
Downloaded from ang.sagepub.com at UNIV OF PITTSBURGH on March 14, 2015
264
Angiology 66(3)
3. Douglas PS, Patel MR, Bailey SR, et al. Hospital variability in the rate of finding obstructive coronary artery disease at elective, diagnostic coronary angiography. J Am Coll Cardiol. 2011;58(8):801-809. 4. Levitt K, Guo H, Wijeysundera HC, et al. Predictors of normal coronary arteries at coronary angiography. Am Heart J. 2013; 166(4):694-700. 5. Mintz GS, Painter JA, Pichard AD, et al. Atherosclerosis in angiographically ‘‘normal’’ coronary artery reference segments: an intravascular ultrasound study with clinical correlations. J Am Coll Cardiol. 1995;25(7):1479-1485.
6. Marchandise B, Bourassa MG, Chaitman BR, Lesperance J. Angiographic evaluation of the natural history of normal coronary arteries and mild coronary atherosclerosis. Am J Cardiol. 1978;41(2):216-220. 7. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines. J Am Coll Cardiol. 2014;63(25 Pt B): 2889-2934.
Downloaded from ang.sagepub.com at UNIV OF PITTSBURGH on March 14, 2015
