Abstract
Objectives. Ambulatory systolic–diastolic pressure regression index (ASDPRI) is a composite marker of cardiovascular properties. The study was conducted to investigate the relationship between ASDPRI and cardiovascular events in patients with significant coronary atherosclerosis confirmed in angiography. Methods. Associations between ASDPRI and cardiovascular events were examined in 891 subjects referred for diagnostic coronary angiography. ASDPRI was calculated as 1 minus the slope of the linear relation between 24-h DBP and 24-h SBP. Results. During follow-up (median 6.7 years), 135 acute coronary syndromes (ACS), including five deaths and 55 strokes occurred in the studied group. There was a higher 24-h ASDPRI in patients with ACS than in patients with no ACS (0.35 ± 01 vs 0.30 ± 0.1, p < 0.01); 24-h ASDPRI was the independent predictor for ACS (OR = 4.0; 95% CI 1.3–12.0). Conclusions. ASDPRI has an important role as a risk factor of ACS in patients with coronary atherosclerosis.
Introduction
Recently published large meta-analysis confirmed the crucial role of the ambulatory systolic–diastolic pressure regression index (ASDPRI) in the prognosis for atherosclerosis-dependent cardiovascular (CV) events, especially strokes (Citation1,Citation2). The role of ASDPRI to be a parameter of arterial stiffness is doubtful but it is considered a composite marker of CV properties (Citation1). Existing observational studies have been performed mainly in patients with hypertension or diabetes, but none of them included patients with confirmed atherosclerosis. Atherosclerosis is undeniably related to changes in arterial structure leading to arterial dysfunction, which enhances CV risk. Therefore, the present study was conducted to investigate the relationship between ASDPRI and CV events in patients with significant coronary atherosclerosis confirmed in angiography.
Methods
From June 2003 to August 2006, the study recruited 891 consecutive individuals with ≥ 70% coronary artery stenosis (CAS) of at least one coronary artery in angiography. Elective angiography was performed in patients who were referred to our department with typical angina symptoms and/or signs of myocardial ischemia in the non-invasive diagnostic procedures (ECG stress test, echocardiographic stress test or myocardial perfusion scintigraphy stress test) to evaluate the indication for invasive treatment (CABG or PCI). Subjects with atrial fibrillation or atrial flutter, congestive heart failure of NYHA class III or IV, significant valvular heart disease or valvular heart disease qualifying the patient for cardiosurgery, renal insufficiency with a creatinine level ≥ 2.0 mg/dl, and other chronic diseases leading to limited life expectancy were excluded. The study protocol was approved by the Ethics Committee of the Medical University of Gdansk. In a period of 2–4 weeks after coronary angiography, 24-h ambulatory BP monitoring was performed (SpaceLabs 90210, SpaceLabs Inc., Redmond, Washington, USA) with BP readings set at 20-min intervals (06:00–18:00 h) and at 30-min intervals (18:00–06:00 h). The non-dominant arm was used for measurement with cuff size adjusted to arm circumference (adult cuff 27–34 cm or large adult cuff 35–44 cm). All blood pressure recordings were obtained on working days and patients were instructed to maintain their usual activities but to refrain from strenuous exercise and emotional burden, and to hold the arm still by the side during blood pressure measurement and to return to the hospital 24 h later. The participant had no access to the ambulatory blood pressure values.
ASDPRI was calculated as 1 minus the slope of the linear relation between DBP and SBP, a value proposed by of Li et al. (Citation3) and Dolan et al. (Citation4). According to ASDPRI, the study group was divided into tertiles.
The subjects were followed from the dates of coronary angiography until December 31, 2011. The follow-up was performed during clinic visits. For the patients who were not able to come for the clinic visit, phone contact was performed. Data about comorbidities were verified by review of hospital discharge cards and if the hospital discharge cards were not available, it was verified by information from National Polish Health Service. Stroke diagnosis was performed according to European Stroke Organization guidelines, and acute coronary syndromes (ACS) were diagnosed according to European Society of Cardiology guidelines (Citation5–7). CV events included myocardial infarction and unstable angina. Major adverse CV events (MACE) included myocardial infarction, unstable angina, stroke and CV death.
Data from groups of subjects were compared using the Student t-test for unpaired observations and the χ2 test of proportions. Average differences in the tertiles of ASDPRI were compared by analysis of variance (ANOVA) using the Tukey HSD test. The logistic regression model was used to identify predictors of ACS in the study group. Variables were selected in a stepwise forward selection manner with entry and retention set at a significance level of 0.05. The risk of a variable was expressed as an odds ratio (OR) with a corresponding 95% confidence interval (CI). Throughout the text, the symbol ± refers to the standard deviation (SD) of the mean and p < 0.05 was taken as the level of statistical significance.
Results
During follow-up (median 6.7 years, 5th–95th percentile interval, 5.4–7.8 years), 135 ACS (44 unstable angina and 91 myocardial infarctions), including five deaths and 55 strokes (11 deaths), occurred in the studied group. The median period from inclusion up to ACS was 1.6 years (5th–95th percentile interval, 0.1–6.1 years), and up to stroke was 3.5 years (5th–95th percentile interval, 0.8–5.7 years).
shows the baseline characteristics of the cohort group. There was a higher 24-h ASDPRI in patients with developed ACS than in patients with no ACS.
Table I. Baseline characteristics of the studies groups.
presents the prevalence of CV events in the tertiles of ASDPRI. The highest tertile characterizes the highest incidence of ACS and MACE in comparison with the lowest tertile.
Table II. Cardiovascular events and mortality in 24-h ASDPRI tertiles.
After adjustment for sex, age, diabetes mellitus, history of myocardial infarction and antihypertensive treatment [beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, diuretics, calcium-channel blockers], the independent predictor from clinical variables in the logistic regression model for ACS was 24-h ASDPRI (OR = 3.6; 95% CI 1.2–11.0), for stroke was 24-h diastolic blood pressure (OR = 1.04; 95% CI 1.0–1.1), for MACE was 24-h ASDPRI (OR = 2.5; 95% CI 1.2–7.9) and age (OR = 1.1; 95% CI 1.0–1.2), and for all-cause death was 24-h ASDPRI (OR = 2.7; 95% CI 1.2–9.9).
Discussion
ASDPRI is a composite index reflecting CV properties. Previous studies have confirmed the crucial role of this parameter in predicting strokes and CV mortality in patients with hypertension or diabetes as well as in general populations (Citation4,Citation8–11). To date, it has not been the purpose of any clinical trials to evaluate ASDPRI as a predictor of CV events in patients with significant coronary atherosclerosis established by angiography.
To our knowledge, the present study is the first to show the important role of ASDPRI as a predicting factor for ACS in subjects with confirmed coronary atherosclerosis. Hansen et al. showed that there was no relationship between ASDPRI and coronary heart disease or CV events in a random sample of 1829 subjects in 9.4 years of follow-up (Citation8). In contrast to our study, Hansen et al. (Citation8) included subjects randomly recruited from the general population. In that study sample, only less than 10% of subjects had a history of CV disease, about 50% a history of hypertension, about 3% diabetes, and only about 25% of subjects were taking antihypertensive drugs. The difference in the structure of the study populations is likely to be connected with the significant relationship between ASDPRI and ACS in the present study. Furthermore, our results are consistent with the findings from the research included hypertensive population in which ASDPRI was correlated with CV events (Citation10). However, in the study the relationship between ACS and ASDPRI was not reported.
In the present study, ASDPRI was not related to incidence of stroke. This fact may be connected with medications. The study population characterizes a high percentage of treated individuals. Over 90% of patients were taking acetylsalicylic acid and lipid-lowering drugs, over 80% were taking beta-blockers and over 70% were taking ACE inhibitors. Likewise, Muxfeldt et al. did not observe any prognostic effect of ASDPRI on cerebrovascular events in the intensively treated hypertensive population (Citation12). The results of the present study and those of the study of Muxfeldt et al. suggest that treated hypertensive subjects are likely to be more effectively protected against cerebrovascular events than against CV events. Clinical trials assessing the influence of particular groups of antihypertensive drugs on ASDPRI and CV and cerebrovascular events are needed.
The limitation of this study is an inability to assess the influence of drugs and their dosages on ASDPRI and the occurrence of end points. Although groups with ACS and those without ACS did not differ in prevalence of treatment with particular antihypertensive and anti-atherosclerotic drugs, analysis of drug dosages was not performed. However, it should be emphasized that in the present study there was no statistical difference in clinical variables including 24-h blood pressure values and lipid fractions between ACS and non-ACS groups.
In conclusion, the results of the present study revealed the important role of ASDPRI as a risk factor of ACS in patients with coronary atherosclerosis. In contrast to studies performed in general populations, our results did not confirm the relationship between ASDPRI and stroke in this group of patients. However, more research is needed to determine the influence of antihypertensive and anti-atherosclerotic treatment on ASDPRI in patients with established atherosclerosis.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
This study was supported by state committee for scientific research – KBN from the Ministry of National Education in Poland.
Related Research Data
References
- Kollias A, Stergiou GS, Dolan E, O’Brien E. Ambulatory arterial stiffness index: A systematic review and meta-analysis. Atherosclerosis. 2012.
- Aznaouridis K, Vlachopoulos C, Protogerou A, Stefanadis C. Ambulatory systolic–diastolic pressure regression index as a predictor of clinical events: a meta-analysis of longitudinal studies. Stroke. 2012;43:733–9.
- Li Y, Wang JG, Dolan E, Gao PJ, Guo HF, Nawrot T, et al. Ambulatory arterial stiffness index derived from 24-hour ambulatory blood pressure monitoring. Hypertension. 2006;47: 359–64.
- Dolan E, Thijs L, Li Y, Atkins N, McCormack P, McClory S, et al. Ambulatory arterial stiffness index as a predictor of cardiovascular mortality in the Dublin Outcome Study. Hypertension. 2006;47:365–70.
- Olsen TS, Langhorne P, Diener HC, Hennerici M, Ferro J, Sivenius J, et al. European Stroke Initiative Recommendations for Stroke Management – update 2003. Cerebrovasc Dis. 2003;16:311–37.
- Bertrand ME, Simoons ML, Fox KA, Wallentin LC, Hamm CW, McFadden E, et al. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2002;23:1809–40.
- Van de Werf F, Ardissino D, Betriu A, Cokkinos DV, Falk E, Fox KA, et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2003;24: 28–66.
- Hansen TW, Staessen JA, Torp-Pedersen C, et al. Ambulatory arterial stiffness index predicts stroke in a general population. Journal of hypertension 2006;24:2247–53.
- Kikuya M, Staessen JA, Ohkubo T, et al. Ambulatory arterial stiffness index and 24-hour ambulatory pulse pressure as predictors of mortality in Ohasama, Japan. Stroke; a journal of cerebral circulation 2007;38:1161–6.
- Gosse P, Papaioanou G, Coulon P, Reuter S, Lemetayer P, Safar M. Can ambulatory blood-pressure monitoring provide reliable indices of arterial stiffness? American journal of hypertension 2007;20:831–8.
- Palmas W, Pickering TG, Teresi J, et al. Ambulatory blood pressure monitoring and all-cause mortality in elderly people with diabetes mellitus. Hypertension 2009;53: 120–7.
- Muxfeldt ES, Cardoso CR, Dias VB, Nascimento AC, Salles GF. Prognostic impact of the ambulatory arterial stiffness index in resistant hypertension. Journal of hypertension 2010;28:1547–53.