Predictors of Coronary Artery Disease Progression among High-risk Patients with Recurrent Symptoms.

BACKGROUND: Despite the availability of new potent medical therapies, the rate of progression of angiographic coronary artery disease (CAD) is not well described. The aim of this analysis is to describe the rate and predictors of progression of CAD among patients with recurrent symptoms.
MATERIALS AND METHODS: We reviewed 259 patients (mean age 61 ± 11 years, 70% males) who underwent two coronary angiograms between 2008 and 2013. Progressive CAD was defined as obstructive CAD in a previously disease-free segment or new obstruction in a previously nonobstructive segment. Patients who had coronary artery bypass surgery between these two angiograms were excluded from the analysis. Multivariate logistic regression was used to determine the independent predictors of progression of CAD.
RESULTS: The included cohort had a high prevalence of coronary risk factors; hypertension (71%), diabetes (69%), and dyslipidemia (75%). Despite adequate medical therapy, more than half of the patients (61%) had CAD progression. Using multivariate logistic regression, a drop in the left ventricular ejection fraction (LVEF) by more than 5% was the predictor of CAD progression (adjusted odds ratio 5.8, P = 0.042, 95% confidence interval 1.1-31.2).
CONCLUSION: Among high-risk patients with recurrent symptoms, the short-term rate of progression of CAD is high. A drop in LVEF >5% is a predictor of CAD progression. Further studies are needed to determine the prognostic value of CAD progression in the era of potent medical therapy.

INTRODUCTION

Coronary atherosclerosis is the leading cause of mortality and morbidity.[12] Coronary artery disease (CAD) progression may explain the severity of the progressive stenotic coronary arteries. Progressive stenotic lesions occur either in an initially normal coronary segment or previously diseased vessel. This is usually associated with rapid acute cardiac events leading to angina pectoris, acute myocardial infarction, and sudden cardiac death.[34]

Coronary angiography, as a diagnostic invasive modality, allows for an accurate detection and exclusion of CAD. It demonstrates the coronary morphology, determines the lesion, and shows its severity.[56] A significant group of patients undergoes a repeated coronary angiography during their life course. Repeated assessment of the coronaries provides an opportunity to study the progression of atherosclerosis over time.[78] These changes were related to the severity of initial angiography, the coronary endothelial function, and ongoing pathophysiologic processes.[910]

A series of risk factors including lifestyle, metabolic abnormalities, and other associated diseases has been associated with the incidence of CAD, but their role in the progression of CAD is not very clear.[1112]

In view of the limited knowledge about the predictors of CAD progression, the aim of this analysis is to describe the rate and predictors of progression of CAD in patients with recurrent symptoms.

MATERIALS AND METHODS

Study population

We conducted a retrospective study including 259 patients who had two clinically indicated coronary angiographies at least 1 year apart between 2008 and 2013. Patients with obstructive CAD at the baseline angiogram (more than 70% stenosis) or those who had coronary artery bypass grafting between the two angiograms were excluded from the study. Baseline characteristics (height, weight, and body mass index [BMI]), conventional cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, and prior history of peripheral vascular disease), echocardiographic parameters (ejection fraction, right ventricular systolic pressure, and presence of diastolic dysfunction), used mediations (beta-blockers, statins, clopidogrel, and angiotensin-converting enzyme inhibitors) and laboratory results (cholesterol, triglyceride, and high- and low-density lipoproteins) were collected. Most of patients were under regular follow-up in their specialized cardiac clinics during the period between the two angiographic studies.

Coronary angiographic assessment

The two coronary angiograms were reviewed. Evaluation of the coronary arteries was per segment based using the 17 anatomical segments.[13] Segments were coded according to the degree of obstruction from normal, nonobstructive (<70% stenosis) to obstructive disease (>70% stenosis).

Definition of coronary artery disease progression

Progressive CAD was defined as new obstructive CAD in a previously disease-free segment or new obstruction in a previously nonobstructive segment on consecutive angiographic studies.

Statistical analysis

The continuous variables were reported as mean ± standard deviation, and the categorical variables were reported as frequencies and percentages. Chi-square test was used to assess the significance of the categorical data and independent sample t-test for the contentious data. Multivariate logistic regression was used to detect the predictors of CAD progression. Cofounders' selection was based on both univariate analysis and clinical judgment, including age, gender, hypertension, diabetes, dyslipidemia, ejection fraction on echocardiography, and diastolic dysfunction. The results considered significant with a significance level <0.05. The data analysis was done using SPSS, version 21 (IBM Statistics, IL, USA).

RESULTS

A total of 259 patients (mean age was 60 ± 11 years and 69.5% were male) had two clinically indicated angiographic studies. The mean duration between the two angiograms was 30 ± 14 months (12–64 months apart). In the initial angiogram, most patients had evidence of nonobstructive CAD with only 14 patients (5.4%) having disease-free coronary arteries. A total of 159 (61.4%) patients had evidence of progression of CAD. At the baseline, the mean ejection fraction on the echocardiography was 47 ± 10. One-third of patients had a systolic blood pressure more than 140 mmHg and BMI more than 30 kg/m2.

In univariate analysis, male patients, history of prior myocardial infarction, and patients with systolic heart failure have a higher prevalence of progressive CAD (75%, 20%, and 18% vs. 61%, 11%, and 4%, respectively). Most of study cohort had a control risk factors, (60%) had low-density lipoprotein (LDL) <100 mg/dl, (65%) had triglyceride <150 mg/dl, and (80%) had cholesterol <200 mg/dl [Table 1].

Table 1

Progressive and nonprogressive coronary artery disease; traditional cardiovascular risk factor distribution

In a multivariate logistic regression, a drop in the left ventricular ejection fraction (LVEF) >5% was a predictor of CAD progression (adjusted odds ratio 5.8, 95% confidence interval 1.1–31.2, P = 0.042) [Figure 1].

Figure 1

Reduction of the left ventricular ejection fraction in the interval period between the two angiographies with rate <5 in difference has a good statistical relation with the progression of the coronary artery lesion that can be utilized as a predictor and useful on regular follow-up

DISCUSSION

Our paper shows that the rate of progression among high-risk patients with recurrent symptoms is high. Our study demonstrated that a drop of the ejection fraction of more than five present using echocardiography in a symptomatic patient is a good predictor for the CAD progression.

Despite comprehensive risk factor intervention, progression of CAD was up to 77.9% in the SWISS II study.[14] Haft and Bachik[15] reported that the incidence of progression in symptomatic patients was 58.8%. Moise et al.[16] showed that a progression rate of 15% for patients with initially normal coronaries at baseline and 50% for those with initial minimal CAD at baseline. Our study progression rate lies in between. This can be approached by the differences in the current lifestyle, reliability in using medication, and appropriate management and risk factor.

The accuracy of the predictive investigation and the investigation used for evaluation of the coronary progression are the leading parts. We labeled progression in our study based on an angiographic assessment. Nissen et al.[17] used an intravenous ultrasound in the initial assessment. They got that intensive LDL cholesterol (LDL-C) lowering with high-dose statin therapy holds atheroma progression. Furthermore, other analysis achieved LDL-C levels <70 mg/dl with a regression on forming atheroma.[17] In our study, the significant results in predicting CAD progression were functional showed on echocardiographic finding. Besides, it gives a lightening pathophysiological process of the disease.

The crucial role of CAD risk factors in the pathogenesis of initial atherosclerotic cardiovascular diseases, some previous studies demonstrate that the intensive monitoring lipid profile and blood pressure, managing the causes through regular follow-up, and controlling lifestyle can decrease the rate of progression or even promote the atherosclerosis regression.[18] Other studies highlighted a direct relationship between reduction in LDL-C and cardiovascular morbidity and mortality.[19] Therefore, recent guidelines focus on stain therapy as a principal target for primary and secondary prevention of cardiovascular disease.[17]

Benefits and limitations

On the other hand, the coronary angiography assessment could underestimate the presence of the occluded CAD. These raised with small size coronaries, contrast dilution, or with technical complexities. Furthermore, the normal coronary segments could easily be missed in the diffuse nature of the CAD.

CONCLUSION

Among high-risk patients with recurrent symptoms, the short-term rate of progression of CAD is high. A drop in LVEF >5% is the best predictor of progression of CAD. Further studies are needed to determine the prognostic value of CAD progression in the era of potent medical therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.