Our data demonstrate that higher LVM and RWT in adolescents and young adults are associated with increased arterial stiffness independently of traditional CV risk factors such as age, sex, obesity, BP, lipids and metabolic control. There is also a trend for a higher prevalence of eccentric hypertrophy in the adolescents and young adults with stiffer arteries which may be driven by the greater level of adiposity in the stiff artery group.
Abnormal LVM and geometry are well-established risk factors for CV events.(7
) Hypertensive adults have a higher prevalence of left ventricular hypertrophy (LVH)(7
) but increased arterial stiffness is also a risk factor for development of LVH independent of BP levels.(29
) Even in healthy adults, a positive relationship is found between arterial stiffness measured by PWV and LVM(30
) that remains after adjustment for traditional CV risk factors.(31
) Alterations in wave reflections combined with increased central stiffness may also contribute to LVH. Studies in hypertensive adults(32
) found a significant correlation between AIx and LVM. The relationship was independent of BP in males although the relationship was not seen in older subjects (> 65 years of age); AIx tends to plateau around age 60 regardless of continued changes in CV risk factors.(32
The importance of arterial stiffness in the evolution of LVH is evident in intervention studies in hypertensive adults. In the REASON study, 212 subjects were randomized to either an angiotensin converting enzyme (ACE) inhibitor or a beta-blocker.(34
) The subjects on the ACE inhibitor had greater reduction in LVM than those on a beta-blocker (−13.6 v −4.3 g, P = .027), with the difference retaining significance after adjustment for final BP level.(34
) Improvement in arterial stiffness explained the difference because only ACE inhibition, but not beta-blockade, improved wave reflection (AIx) in this study cohort.(35
) Improvement in other measures of arterial stiffness with treatment of hypertension has also been linked to lower LVM. ACE inhibition in combination with calcium channel blockade improved brachial artery distensibility, resulting in reduced LVM in subjects with mild-to-moderate hypertension.(36
) Similarly, improvement in PWV with anti-hypertensive therapy has been linked to regression of LVH.(37
) These data demonstrate the clinical utility of arterial stiffness measures in optimizing blood pressure treatment to effect the greatest regression of LVM in hypertensive patients.
A link between arterial stiffness and LVM has been identified in other adult diseases. Obese subjects with obstructive sleep apnea were found to have higher LVM and aortic stiffness than subjects with normal sleep studies. Aortic stiffness was an independent determinant of LVM even after adjustment for the respiratory disturbance index.(38
) Similar to data from hypertensive subjects, treatment of obesity with bariatric surgery resulted in parallel improvement in aortic stiffness and LVM.(39
) Diabetic adults tend to have faster carotid-femoral transit time (similar to PWV) and higher AIx (significant in men), indicating increased stiffness. These changes are associated with higher LVM as compared with controls (176 vs 147 gm, p<0.001 females, 199 vs 188 gm, p<0.096 males).(40
) In subjects with chronic kidney disease (CKD), there was a linear rise in LVM across tertiles of PWV and this increase in arterial stiffness remained an independent predictor of LVM after adjustment for renal impairment.(41
) Other investigators found AIx was an independent predictor of LVM in both sexes after adjustment for CV risk factors such as blood pressure.(42
) Prospectively, a higher AIx at baseline predicted greater decline in creatinine clearance after 1-year of follow-up.(43
) In patients with CKD, treatment with medications affecting the renal-angiotensin-aldosterone system (angiotensin receptor blockers) resulted in a decrease in LVM that was associated with a concomitant reduction in PWV and AIx,(44
) providing more supportive evidence to the concept that regression of LVH may be best accomplished through reduction of arterial stiffness.
Few data are available examining the relationship between arterial stiffness and LVM in adolescents and young adults. Patients with bicuspid aortic valve (age 16 to 39 years of age) were found to have higher PWV, reduced aortic root distensibility and significantly increased LVM compared with controls.(45
) Coarctation of the aorta (CoA) may share a genetic and developmental etiology with bicuspid aortic valve disease and has been similarly related to intrinsic arterial stiffness abnormalities. De Devitiis studied patients after repair of CoA at an average age of 19.8 years.(46
) Both LVM and PWV were elevated in patients as compared with controls.(46
) This finding was replicated in a younger cohort (average age 12 years), with elevations in PWV significantly correlated with higher LVM index (84 vs 73 g/m2
) Altered wave reflections may also play a role in development of LVH. When measured with MRI, teenaged subjects with CoA who had augmented systolic wave reflection (similar to increased AIx) had higher LVM than patients without this finding.(48
) Children with renal failure also demonstrate cardiac and vascular abnormalities. A linear increase in carotid thickness, stiffness and LVM was found comparing healthy children (average age 14 years) with those with stable CKD and to youth with severe CKD on dialysis.(49
) Type of dialysis may also be important as one study found a trend for higher LVM in pediatric patients on hemodialysis as compared with peritoneal dialyses with a significantly reduced aortic distensibility in the hemodialysis group.(50
) Therefore, processes that produce significant increases in arterial stiffness, even at a young age, can increase risk for development of LVH. Our study extends these observations by demonstrating a relationship between arterial stiffness and LVM in adolescents and young adults with less severe pediatric diseases including obesity, and obesity-related CV risk factors.
Our cross-sectional study cannot determine if increased arterial stiffness preceded the development of higher LVM or if these abnormalities in CV structure and function developed simultaneously. There may also have been other non-measured confounders (activity pattern and fitness level, for example) which affected the arterial-cardiac relationship. However, our findings are similar to the limited studies performed in youth and parallel results obtained in adults with CV risk factors. Additionally, due to the original study design (examining CV outcomes in diabetics compared with non-diabetic adolescents and young adults) our cohort contains a large proportion of subjects with T2DM. Because there was no difference in LVM among diabetics only, it is possible that the adverse effects of diabetes, either through elevation in traditional CV risk factors or directly on the heart, may have a greater effect on LVM than arterial stiffness. Larger studies are needed to elucidate these relationships. Finally, equipment and expertise in collecting ultrasound measures of carotid stiffness and non-ultrasound measures of arterial stiffness may not be readily available to many pediatric care providers thus limiting the applicability of the GSI calculation to the clinical setting.
In conclusion, adolescents and young adults with a stiffer arterial tree demonstrate a more adverse CV risk profile and higher LVM. The increase in cardiac mass, however, is related to greater arterial stiffness independent of traditional risk factors (demographics, BP, anthropometrics, lipids, inflammation). Because both LVH(7
) and increased arterial stiffness(51
) are significant predictors of CV mortality, addition of arterial stiffness measurements to echocardiography may assist in risk stratification in adolescents and young adults with elevated CV risk factor levels.