Effect of ageing on left ventricular compliance and distensibility in healthy sedentary humans

Abstract

Healthy, but sedentary ageing leads to marked atrophy and stiffening of the heart, with substantially reduced cardiac compliance; but the time course of when this process occurs during normal ageing is unknown. Seventy healthy sedentary subjects (39 female; 21–77 years) were recruited from the Dallas Heart Study, a population-based, random community sample and enriched by a second random sample from employees of Texas Health Resources. Subjects were highly screened for co-morbidities and stratified into four groups according to age: G(21−34): 21–34 years, G(35−49): 35–49 years, G5(0−64): 50–64 years, G(≥65): ≥65 years. All subjects underwent invasive haemodynamic measurements with right heart catheterization to define Starling and left ventricular (LV) pressure–volume curves. LV end-diastolic volumes (EDV) were measured by echocardiography at baseline, −15 and −30 mmHg lower-body negative pressure, and 15 and 30 ml kg(−1) saline infusion with simultaneous measurements of pulmonary capillary wedge pressure. There were no differences in heart rate or blood pressures among the four groups at baseline. Baseline EDV index was smaller in G(≥65) than other groups. LV diastolic pressure–volume curves confirmed a substantially greater LV compliance in G(21−34) compared with G(50−64) and G(≥65), resulting in greater LV volume changes with preload manipulations. Although LV chamber compliance in G(50−64) and G(≥65) appeared identical, pressure–volume curves were shifted leftward, toward a decreased distensibility, with increasing age. These results suggest that LV stiffening in healthy ageing occurs during the transition between youth and middle-age and becomes manifest between the ages of 50 to 64. Thereafter, this LV stiffening is followed by LV volume contraction and remodelling after the age of 65.

Figure 1. Frank–Starling relationship

Global ventricular performance for sedentary subjects in different age groups. Lines represent second linear regressions for G₂₁₋₃₄ (21–34 years) (r²= 0.99), G₃₅₋₄₉ (35–49 years) (r²= 0.96), G₅₀₋₆₄ (50–64 years) (r²= 0.95) and G_≥65 (≥65 years) (r²= 0.97). Note the largest stroke volume index for any pulmonary capillary wedge pressure (PCWP) and substantially upward shifted Starling curve in G₂₁₋₃₄.

Figure 2. Preload recruitable stroke work

Lines represent linear regressions for G₂₁₋₃₄ (21–34 years) (r²= 0.99), G₃₅₋₄₉ (35–49 years) (r²= 0.99), G₅₀₋₆₄ (50–64 years) (r²= 0.99) and G_≥65 (≥65 years) (r²= 0.97). No differences were noted in the slope of preload-stroke work relationships among the 4 groups.

Figure 3. Diastolic pressure–volume relationships

A, pressure–volume curves for G₂₁₋₃₄ (21–34 years) (r²= 0.99), G₃₅₋₄₉ (35–49 years) (r²= 0.99), G₅₀₋₆₄ (50–64 years) (r²= 0.98) and G_≥65 (≥65 years) (r²= 0.99). Note the steeper slope of pressure–volume curve for G₅₀₋₆₄ and G_≥65 compared to G₂₁₋₃₄, suggesting a stiffer ventricle. Although the LV chamber compliance in G₅₀₋₆₄ and G_≥65 appeared to be identical, LV pressure–volume curves shifted leftward with increasing age. B, transmural pressure–volume curves for G₂₁₋₃₄ (r²= 0.95), G₃₅₋₄₉ (r²= 0.98), G₅₀₋₆₄ (r²= 0.97) and G_≥65 (r²= 0.97). Note the steeper slope of the transmural pressure–volume curve for G₅₀₋₆₄ and G_≥65 compared to G₂₁₋₃₄, also suggesting a stiffer ventricle. Note the different scale used for Fig. 3A and B.

Figure 4. Relationship between LV stiffness constant and continuous age

LV stiffness constant was positively associated with age. •, male and ○, female.