Edward G. Lakatta

Aortic Stiffness Is Associated With Visceral Adiposity in Older Adults Enrolled in the Study of Health, Aging, and Body Composition

The central arteries stiffen with age, causing hemodynamic alterations that have been associated with cardiovascular events. Changes in body fat with age may be related to aortic stiffening. The association between vascular stiffness and body fat was evaluated in 2488 older adults (mean age, 74 years; 52% female; 40% black) enrolled in the Study of Health, Aging, and Body Composition (Health ABC), a prospective study of changes in weight and body composition. Clinical sites were located in Pittsburgh, Pa, and Memphis, Tenn. Aortic pulse wave velocity was used as an indirect measure of aortic stiffness. A faster pulse wave velocity indicates a stiffer aorta. Body fat measures were evaluated with dual energy x-ray absorptiometry and computed tomography. Independent of age and blood pressure, pulse wave velocity was positively associated with weight, abdominal circumference, abdominal subcutaneous fat, abdominal visceral fat, thigh fat area, and total fat (P <0.001 for all). The strongest association was with abdominal visceral fat. Elevated pulse wave velocity was also positively associated with history of diabetes and higher levels of glucose, insulin, and hemoglobin A1c (P <0.001 for all). In multivariate analysis, independent positive associations with pulse wave velocity were found for age, systolic blood pressure, heart rate, abdominal visceral fat, smoking, hemoglobin A1c, and history of hypertension. The association between pulse wave velocity and abdominal visceral fat was consistent across tertiles of body weight. Among older adults, higher levels of visceral fat are associated with greater aortic stiffness as measured by pulse wave velocity.

Mechanisms of Relaxation: Perspectives from Studies in Single Cardiac Cells

Sarcomere shortening and relaxation in heart cells depend upon myofilament interaction, that is, crossbridge formation and dissociation between actin and myosin, which is regulated in a complex manner by numerous mechanico-chemical factors (Figure 16-1). These factors include the extent of Ca2+ binding to troponin C, concentrations of ATP, inorganic phosphate, Mg2+ and H+, isoforms of myosin and troponins, the phosphorylation status of some of these, sarcomere length, and the mechanical load borne [1]. Intracellular loading factors, that is, forces, are generated within sarcomeres and opposed by other intracellular structures, and other tissue loading factors are generated by intercellular connections and extracellular matrix, for example, by the amount, type, and geometry of collagen network.

Functional Sequelae of Diastolic Sarcoplasmic Reticulum Ca2+ Release in the Myocardium

Routine cardiac catherization and angiography in patients with cardiac disease have permitted the measurement of not only systolic function but also of ventricular filling pressure and volume. The advent of ultrasound and radionuclide techniques has rendered the assessment of diastolic function, i.e. filling rates and volumes, and systolic function still more common. While these technological developments have verified the notion of variable diastolic compliance and the coexistence of “abnormal diastolic” function with normal or abnormal systolic “function,” the nature of the former and its relation to the latter still remain obscure.

Novel Perspectives on Cardiac Pacemaker Regulation: Role of the Coupled Function of Sarcolemmal and Intracellular Proteins

Recent experimental and theoretical studies demonstrate that the sinoatrial node cells (SANCs), the primary pacemaker cells of heart, operate as a complex system of functionally coupled sarcolemmal and intracellular proteins. The proteins of this system dynamically (beat-to-beat) interact throughout the entire pacemaker cycle via membrane voltage and local subsarcolemmal Ca2+ changes. Furthermore, functions of the sarcolemmal (SL) electrogenic proteins and sarcoplasmic reticulum (SR) Ca2+ cycling proteins are coupled and regulated enzymatically via Ca2+-, PKA-, and CaMKII-dependent protein phosphorylation. The system is not only robust (i.e., fail-safe within wide parameter range), but simultaneously flexible, because the autonomic neural modulation of the beating rate, via G protein-coupled receptor (GPCR) signaling, acts upon the very same regulatory factors (i.e., the coupling factors, Ca2+, PKA, and CaMKII) that ensure and regulate robust system function in the basal state. This chapter summarizes the experimental and theoretical evidences for this novel pacemaker concept.