Arterial compliance plateaus in healthy aging women--in time for preventive treatment.

Abstract

The upward trend in proportion of cardiovascular diseases with advancing age represents a growing burden to society and health care systems worldwide making it crucial to identify optimal lifetime period for effective prevention. The process of healthy vascular ageing can be distorted to its unsuccessful form that causes structural and functional alterations in the vasculature resulting in decreased arterial compliance, capacity to strain and accommodate changes in blood pressure (BP). It has been shown that the turn point is most frequently associated with risk factors such as age, sex, race, family history, hypertension, diabetes mellitus, heart disease, serum lipid levels, central obesity, physical inactivity, alcohol abuse and smoking. , , Deficiency of systematic vascular research in women, 2, 3 encouraged design of this study to assess the temporal outline of common carotid mechanics with vascular ageing profile for women using several biomarkers since they show a tendency for age-associated changes.1 One hundred clinically healthy women from Croatia, aged from 25 to 75 years and subdivided into five 10-year age groups, participated in the study after they signed the Informed consent previously approved by the Hospital Ethic Committee. Exclusion criteria were any previously established vascular disease and/or evident early atherosclerotic changes (IMT of the distal CCA wall > 0.8 mm) but included controlled hypertension (23.08%), higher BMI (29.81%) and smoking (19.23%). The mean of the three non-invasive brachial BP readings was used and pulse pressure (PP) calculated.1 Ultrasound measurements were performed on distal CCA (1.5 cm proximal to the carotid bifurcation) with 13 MHz linear transducer on Aloka 5500-SSD Prosound (Aloka CO., LTD.) in B and M modes using standard protocols and recommendations. Evaluated carotid biomarkers were: IMT, systolic and diastolic inter-adventitial diameters (CID) and the difference between the two (CIDc) as measures of arterial compliance ; and circumferential arterial strain (CAS) and beta stiffness index (BSI) as measures of carotid stiffness. The latter two were calculated using standard formulas. The Analysis of Variance (RM-ANOVA) was conducted on the BSI, BP and BMI across age groups after the Kolmogorov - Smirnov and Bartelletov - Box tests confirmed the normality of distribution. Multiple regression analysis and nonlinear regression modeling were conducted using Curve Expert 1.3. Statistical significance was verified by F-test (α=0.05, F0=10.13). Average BP was 121.88±11.45/76.83±6.72 mmHg (24% of women were hypertensive), average PP was 45.05±7.09 mmHg and average BMI was 25.19±3.98 kg/m2, 29.81 % of women were overweight (>25 kg/m2) and 12.5 % obese (>30 kg/m2). Twenty women (20%) were active smokers (average 16.85 pack-year) and 64% were never smokers. CID was rather uniform bilaterally, and ranged between 6.507.05 mm (right) and 6.206.78 mm (left). Figure 1 shows detailed descriptive data for IMT, CIDc, CAS and BSI bilaterally across age groups with significant side-to-side difference. Multivariate regression analysis showed no association of BSI, BP or BMI to investigated parameters across age groups (ANOVA, F(3.16)=0.19, p=0.65), as was previously reported. We confirmed a very strong linear (r=0.994, S=0.012, F=122.74) temporal IMT increase of average 0.0021±0.0003 mm/year. Linear regression was also found in BSI-age analysis (r=0.986, S=0.479, F=51.34) with average yearly increase of 8.48±0.38. This is the first report of very strong linear relationship of increased stiffness in a muscular artery in women, so far it was reported that stiffness increases proportionally to age only in large elastic arteries. Furthermore, modeling of CIDc and CAS data showed a cubic spline behavior which is another novel and most intriguing result of this study. We described these cubic curves by three separate linear functions: slope coefficients were equal bilaterally for CAS (b= -0.002) and CIDc (b= -0.009). Inflection point at which the curvature changes the sign of form is followed by value plateau between 40-60 yrs after which a sharp decrease of CAS and CIDc were noted again, suggesting the existence of temporal biological stability for CAS and CIDc with no observed side-to-side difference. Our data confirmed the existence of arterial remodeling due to increase in PP that altered intrinsic CCA viscoelastic properties. Such changes were previously established as early indicators of vascular damage and vascular event prediction.7, Additionally, change of one standard deviation for CIDc and BSI indicated increased risk of hypertension development by 15% (ARIC prospective study). Our ultrasound based modeling in women suggests that temporal window between 40-60 yrs of age is the optimal timing for the beginning of preventive and protective cerebrovascular strategies during which carotid strain and compliance remain stable. Moreover, reported results would help to create “population's vascular profile“ that could allow the assessment of personal biological vascular age.