Ambulatory arterial stiffness index as a predictor of cardiovascular events.

Ambulatory arterial stiffness index as a predictor of cardiovascular events. A meta-analysis of longitudinal studies. Konstantinos Aznaouridis, Charalambos Vlachopoulos, Christodoulos Stefanadis. 1 st Department of Cardiology, Hippokration Hospital, Athens Medical School, Athens, Greece. August 31, 2011 No conflict of interest

Arterial stiffness and risk stratification Increased pulse wave velocity is added to the list of factors influencing prognosis as an early index of hypertension-related target organ (large artery) damage

Arterial stiffness and risk stratification

Ambulatory BP and risk stratification Prospective studies have shown that a higher ambulatory systolic or diastolic BP predicts CV events even after adjustment for office BP. Clement DL et al, N Engl J Med. 2003;348:2407-2415. Fagard RH et al, Hypertension. 2008;51:55-61. Recently, a large epidemiological study showed that ambulatory systolic pressure, and especially nighttime pressure, is an important predictor of cardiovascular events and all-cause mortality. Boggia J et al, Hypertension. 2011;57:397-405.

Ambulatory arterial stiffness index (AASI) AASI: 1 minus the slope of diastolic on systolic pressure during 24- hour ambulatory monitoring Dolan E et al, Hypertension. 2006;47:365-370 Li Y et al, Hypertension. 2006;47:359-364

Ambulatory arterial stiffness index (AASI) There is a general impression that AASI has a significant predictive role based on the results of individual studies. However, no overall quantitative estimate of this role exists.

Purposes of meta-analysis To calculate quantitative estimates of the predictive value of AASI for outcomes (total CV events, stroke, allcause mortality). To investigate whether publication bias could have affected the estimated predictive ability of AASI

Outcomes of meta-analysis 1) total CV events 2) stroke 3) total (all-cause) mortality Study eligibility 1) full-length publications in peer-reviewed journals 2) evaluated AASI 3) reported a combined CV outcome or stroke or total mortality

Literature search Systematic review of the English literature in the PubMed and Cochrane databases until February 2011. The search terms were ambulatory arterial stiffness, ambulatory arterial stiffness index, arterial elasticity, or arterial stiffness and prediction, risk, death, mortality, outcome, or events.

Data & Statistics Aggregate data reported in published articles were used for analysis (no data of individual patients). The risk estimates of each study were reported as a hazard ratio, relative risk (RR) or odds ratio. The predictive ability of AASI was evaluated for - high (vs low) AASI - increase of 1 SD Patients were allocated to high or low AASI groups according to cutoffs provided by each study (median, upper tertile or quartile, optimal cutoff derived by ROC curves) When possible, adjusted risk estimates from multivariate models were used to control for possible selection bias in the original studies. According to the observed heterogeneity, a fixed or a random effects model was used to obtain the pooled RR. All analyses were performed with Comprehensive Meta Analysis Version 2 (Biostat, Englewood, New Jersey).

Results Qualitative summary Our search identified 58 publications, which were narrowed by preliminary review to 19 potentially relevant original articles. Of those, 12 studies were excluded because of 1) cross-sectional study design (n = 11), or 2) had the whole population or part of the population in common (n=1). Our meta-analysis included 7 original articles following 20,505 subjects for a mean follow-up of 7.8 years All studies were published since 2006

Author, year Population- Sample size Followup Events AASI cut-off (high vs. low) Dolan 2006 Hypertension (most) (N=11,291) 5.3 y (median) 566 CV deaths (151 stroke deaths, 358 cardiac deaths) upper boundary of the 95 prediction interval of individual data points in relation to age Hansen 2006 Community based adults (half hypertensives) (N=1,829) 9.4 y (median) 212 CV events 40 strokes 150 CHD events upper boundary of the 95 prediction interval of individual data points in relation to age Kikuya 2007 General population (half hypertensives) (N=1,542) 13.3 y (median) 345 deaths 126 CV deaths 63 stroke deaths upper quartile compared with whole population Ben-Dov 2008 Hypertension (most)(n=2,918) 7.0 y (mean) 215 deaths (all-cause) median Palmas 2009 Elderly with diabetes (N=1,178) 6.6 y (mean) 287 deaths (110 CV deaths) upper vs. lower tertile Bastos 2010 Hypertension (N=1,200) 8.2 y (mean) 62 deaths 152 CV events 79 strokes median Muxfeldt 2010 Resistant hypertension(n=547) 4.8 y (median) 65 deaths 45 CV deaths 101 CV events median

Results (high vs low AASI) CV outcome Stroke All-cause mortality Compared to low AASI, the pooled RR of total CV events, stroke and all-cause mortality for high AASI patients was 1.51, 2.01 and 1.25, respectively.

Results (total CV events vs stroke) High vs. low AASI The pooled RR was higher for stroke than for total CV events

Results (1 SD increase) CV outcome Stroke For an increase in AASI by 1 SD, the pooled RR of total CV events and stroke is 1.15 and 1.30, respectively (the risk increases by 15% and 30%).

Results (hypertensives vs normotensives) RR of stroke for a 1 SD-increase in AASI The pooled RR of stroke was significantly higher in normotensives

Results Publication bias analysis - Funnel plots of precision - Trim-and-fill method (imputes theoretically missing studies and recalculates the pooled RR) Publication bias is not sufficient to influence our findings in a meaningful way

Summary of findings In populations with high AASI, the risk of CV events, stroke and all-cause mortality is higher compared with the risk in patients with low AASI. The predictive ability of increased AASI is higher for stroke than for total CV events. The predictive value of increased AASI is higher in normotensive patients.

Limitations Use of aggregate summary- data (no data of individual patients). To define high and low AASI, we used the cutoff values used by each study, because there are no established cutoffs for AASI. Although stroke and all-cause mortality were uniformly defined, the definition of total CV events differed among the studies.

Conclusions AASI is a strong predictor of future CV events, stroke and all-cause mortality. Future studies should provide data on a wider range of populations and they should elaborate on the ability of AASI to discriminate, calibrate and reclassify the risk of patients.