Risk Factors For Acs Of Patients

Published Date: 02 Nov 2017

To study the prevalence of patients with hyperfilteration (greater than 120ml/min eGFR) diagnosed with ACS and analyze associations of hyperfilteration with cardiac risk factors and angiographic findings.

INTRODUCTION:

In patients with chronic kidney disease (CKD), cardiovascular disease (CVD) is the most frequent cause of morbidity and mortality [1-2]. Such patients are more likely to experience cardiovascular deaths rather than developing terminal renal failure [2-3]. The risk of cardiovascular mortality, however, is highest in patients with end-stage renal disease (ESRD). More than 50% of deaths among patients with ESRD have been reported due to cardiovascular events [4]. This association between reduced kidney function and cardiovascular events may have several possible explanations.

The glomerular filtration rate (GFR) has been largely accepted as the best overall index of kidney function [5]. The National Kidney Foundation defines CKD as the presence of kidney damage with a persistent reduction in GFR to less than 60 ml per minute per 1.73 m2 of body-surface area [6]. This value represents a reduction by more than half of the normal value of ≈125 ml per minute per 1.73 m2. However, the interpretation of GFR estimates may depend on the clinical presentation [7]. Patients with proteinuria, haematuria, abnormal urinary sediment or other markers of kidney damage or abnormalities on imaging studies or on kidney biopsy have the disease, even if estimated GFR (eGFR) is 60 ml per minute per 1.73 m2 or greater. Likewise, patients with estimated GFR of 60 ml per minute per 1.73 m2 or greater without markers of kidney damage are not likely to have the disease [7].

An interesting finding whilst estimating GFR is seen in a fair amount of individuals who have eGFR values elevated above the normal. Although elevated GFR, or glomerular hyperfiltration, is a frequent finding in patients with diabetes [8] or metabolic syndrome [9-10], the clinical impact of greater-than-normal eGFR yet needs to be elucidated.

Given that impaired renal function is mostly associated with clinical outcomes, a proper relationship between the two extremes of the GFR spectrum with CVD has yet not been established. Especially relevant data from the Pakistani population is nonexistent. A prospective study conducted by Jula et al showed significant relationship of adverse cardiac outcomes in those patients who had a pre-calculated higher GFR.

NICVD is the biggest cardiac hospital in Karachi with a total bed strength of_____. Most of the cases admitted are of acute coronary syndrome. Baseline values such as serum creatinine are taken for most of the patients making the estimation of GFR easier.

We conducted this study to determine the association of increased GFR (greater than 120ml/min) with the number of vessel disease and other demographic factors in patients of acute coronary syndrome admitted during a period of past three years.

Subjects and Methods:

This was a retrospective study was carried out in National institute of Cardiovascular Diseases, Karachi, Pakistan for a period of 3 years from Jan 2009 to Dec 2011 during which a total of 1267 patients admitted into the hospital with the diagnosis of acute coronary syndrome and GFR greater than 90ml/min were enrolled by convenient sampling. All of the patients had undergone coronary angiography to determine the state of their vessels and these findings were associated with increased GFR.

Inclusion: Acute coronary syndrome was diagnosed when the patients had an acute MI, the diagnosis of unstable angina or an ischemic stroke confirmed by history, physical examination, electrocardiographic findings, computed tomographic or magnetic resonance imaging scan and biochemical analysis.

Exclusion: Patients with severe CKD (creatinine clearance [CrCl] 30 ml/min by Cockcroft-Gault formula) and patients with concomitant severe disease, such as neoplasm that was likely to limit life expectancy were excluded. Sudden cardiac death was not included as post-event angiography is not routinely performed. Patients who died during admission before an angiography could be performed were also excluded. Patients whose calculated GFR was below 90ml/min were also excluded.

The demographic data including age, bmi, health status, family history and even serum values like serum creatinine and angiographic findings were obtained from the patient records.

Measurement of Kidney Function: The MDRD equation was used to estimate GFR from the serum creatinine. In additional sensitivity analyses, CrCl was calculated using the Cockcroft-Gault equation using ideal body weight:

Coronary Angiography: Results of coronary angiography as to whether SVD, 2VD, 3VD or none were obtained from the records of the cath lab. The angiography had been performed by skilled interventional cardiologists. Stenosis of greater than 70% for LAD, RCA and 50% for left main was taken as the diagnostic criterion to determine vessel disease status of the patient.

Statistical Analyses: Demographic and clinical factors were summarized and compared between groups of subjects stratified on renal function as evaluated by eGFR. Continuous and categorical variables were compared using the Student t-test, Spearman correlation test and the Chi square test. Data was represented with tables and diagrams.

The study was approved by an institutional review committee.

Results:

A total of 1267 patients were included into the study. A total of 807 patients had an eGFR between 90-120ml/min while 460 subjects had an eGFR above 120ml/min. Mean eGFR of the two groups was 102ml/min and 146ml/min respectively. In general, subjects with the higher eGFR were more likely to be younger (mean age=45.6±7); males; have higher average BMI (30.9± 5.3); and a higher average blood pressure (130/80) than their normal eGFR counterparts. Table 1 shows the distribution with p-values of the student t-test.

Subjects with eGFR greater than 120ml/min were more likely to be diabetics, hypertensives and smokers as compared to their normal counterparts. Refer Table2.

A much higher percentage of patients with eGFR greater than 120 had a positive family history of obesity and cardiac disease as compared to their counterparts. Both these associations were found to be significant (p-value<0.001). However they had a much lesser incidence of previous infarcts. Refer Table2.

Patients with eGFR above 120ml/min reported greater number of cases of single vessel disease upon coronary angiography as compared to their normal counterparts (27.8% vs 21.8%), but reported lesser cases of three vessel disease (24.8% vs 28.5%). 27.8% of the higher eGFR group had no reported vessel disease as compared to the normal participants where 25.9% came clean on angiography. Refer Table 3 for details. The association of GFR with vessel disease was significant (p value=0.036).

Subjects with elevated eGFR between the ranges of 150 ml/min- 175ml/min had the worst angiographic findings with the least negative results (20%) and greatest percentage of SVD (30.5%) and 3VD (30.5%) within all groups of all the patients.

I wanted to include the correlation of eGFR with age, bmi, diabetic years and smoking years. We could make scatter diagrams for them. However I don’t know how to make scatter plot in SPSS.

Please read the results again. Do tell me if any figure can be drawn as such?

Table1: Demographic and physical findings of patients

eGFR less than 90-120

eGFR equal and greater 120

p-value

Total

N= 807

N= 460

Gender (male)

666(82.5%)

395(85.9%)

0.133

Gender (female)

141(17.5%)

65(14.1%)

Age

49.5± 8.5

45.6± 7.8

<0.001

BMI

28.1± 4.4

30.9± 5.3

<0.001

eGFR

102.8

146.2

<0.001

BP

110/80

130/80

-

Table 2: Risk factors for ACS of Patients

eGfr less than 90-120

eGfr equal and greater 120

p-value

N= 807

N= 460

Diabetic

Total

Oral hypoglycemic

Insulin

Diet controlled

203 (25.15%)

120 (26%)

0.875

181 (22.4%)

108 (23.5%)

11 (1.4%)

5 (1.1%)

11(1.4%)

7 (1.5%)

Smoker

230 (28.5%)

139 (30.2%)

0.853

Hypertensive

342 (42.4%)

209 (45.4%)

0.117

FH of cardiac disease

142 (17.6%)

101 (22%)

0.064

FH of Obesity

103 (12.8%)

87 (18.9%)

0.004

Previous infarct

224 (27.7%)

123 (26.7%)

0.863

Table 3: Relationship of eGFR with CVD

eGFR less than 90-120

eGFR equal and greater 120

N= 807

N= 460

NONE

210 (26%)

128 (27.8%)

SVD

176 (21.8%)

128 (27.8%)

2VD

191 (23.7%)

90 (19.6%)

3VD

230 (28.5%)

114 (24.8%)

DISCUSSION:

Decreased GFR has been consistently found to be an independent risk factor for cardiovascular outcomes and all-cause mortality in high-risk populations. Several studies, such as the HOPE trial [11], the Second National Health and Nutrition Examination Survey (NHANES II), the Hypertension Optimal Treatment (HOT) Study [13], and the Atherosclerosis Risk In Communities (ARIC) Study [14] have shown decreased GFR to be associated with increased risk for cardiovascular events. However, the prognostic impact of above-the-normal GFR has not been much studied.

A study by Inrig et al [15] in 8,941 patients with atherosclerotic cardiovascular disease reported an elevated risk of cardiovascular outcomes (MI, stroke, CHF and all-cause mortality) in patients with increased eGFR (estimated by Cockcroft-Gault formula and MDRD). This study showed that among subjects with an eGFR ≥ 100ml/min per 1.73 m2, each 10ml/min per 1.73 m2 increase in eGFR was associated with an increase of 9% of that risk. In Inrig's study the population with eGFR>120ml/min were younger, females and non-white. Whereas in our study they were younger and males as compared to their counterparts. These findings need to be justified… non-whites in American populations constitute blacks, Hispanics, Asians and Indians hence the similar physiology and results. More males in our study just show the greater male dominated pattern of ACS in our society. However we still need to prove why more males.

Other studies have suggested increased eGFR to be associated with other target organ damage. In 111 patients with essential hypertension and normal renal function, glomerular hyperfiltration was associated with a significant increase in left ventricular mass index, suggesting that elevated GFR may be an indicator for early target organ damage in these patients [16]. Elevated eGFR in our population was also associated with hypertension (Diastolic > 100mm Hg) and a mean recorded blood pressure of 130/90 mm Hg as compared to a relatively normal profile in the normal patients. This further increases the risk of adverse cardiac outcomes in patients as was noted in our study.

Another study reported glomerular hyperfiltration in hypertensive patients to increase the risk of developing microalbuminuria [17]. In diabetic patients, glomerular hyperfiltration predicts the subsequent development of nephropathy, independently of the degree of metabolic control [18-19]. Our study showed a greater percentage of diabetics present in the hyperfilteration group as compared to the normal. A majority of these were on oral Hypoglycemics.

Obesity has also been associated with hyperfiltration [20]. A study by Tomaszewski et al suggested that increased metabolic risk in young healthy males is associated with a 6.9-fold increase in the likelihood of glomerular hyperfiltration occurring before the overt manifestations of cardiovascular disease [21]. Indeed our subjects with eGFR>120ml/min had a mean BMI of 31 which by international standards is borderline Obese.

Our patients who demonstrated hyperfilteration also showed a greater positive family history of Obesity and Cardiac disease. They also reported to be more smokers. Indeed elevated GFR may be an early marker of population at risk for cardiovascular events. However due to the retrospective nature of the study it could not be determined whether eGFR was a risk factor for the cardiac outcomes or a mere predictor, nevertheless the association is too strong to be negated.

The association of eGFR with vessel disease came as significant. Our study showed that those with hyperfilteration had greater chance of single vessel disease but lesser of 2VD and 3VD. Moreover their numbers overall for vessel findings were lesser than the normal counterparts. The fact that eGFR was most associated with SVD could be justified by the fact that due to the greater cardiac risk in these patients, they presented early in the course of their disease when the coronary obstructions were minimal but enough to cause ACS events like MI and unstable angina. Meanwhile normal patients usually presented late in the course of their disease when they had multiple blockages all collectively contributing to their cardiac outcomes. eGFR was also associated with a lesser percentage of previous infarcts as compared to the normal. This could also explain why slightly more normal patients reported 2VD and 3VD and lesser SVD. Need references.

Limitations:

Being a retrospective analysis, our study had many limitations of recording bias. They were minimized by tallying the data of the cath lab with the patient files. We used the Cockcroft-Gault and Modification of Diet in Renal Disease (MDRD) equations to estimate GFR in our study [22-25]. Two hypotheses have been suggested to explain the results found in our study. Evidence suggests overestimation of GFR with the Cockcroft-Gault formula, especially in obese individuals, and underestimation of GFR with the MDRD equation. Hence, the difference in cardiac disease analysis among subjects with elevated eGFR may be due to hyperfiltration or alternatively may be identifying a subgroup of subjects in whom kidney function is falsely overestimated.

Conclusion:

eGFR greater than 120ml/min is more common in younger males in our society. Its associated with Diabetes, Hypertension, Obesity, smoking and single vessel disease.