Aging and Cardiovascular Disease

Aging and the Cardiovascular System

• The aging cardiovascular system is examined at structural, functional, and molecular levels.
• Analyzing ECG traces and identifying heart conditions through scenarios enables the evaluation of heart health.

Cardiovascular Disease (CVD) Risk Factors

• CVD encompasses coronary artery disease, stroke, hypertension, heart valve problems, heart failure, cardiomyopathy, and congenital heart conditions.
• Risk factors include race, ethnicity, genetics, gender, age, high blood cholesterol, smoking, physical inactivity, and obesity.
• By 2030 there is an estimated medical cost of $818.1B for additional people having hypertension, coronary heart diseases, stroke and heart failure.
• The global population of people over 65 is 10% of 8 billion people.
• In North America and Europe 17-19% of the population is over 65.
• CVD is a major burden for the older population and on health care systems.

Age as CVD Risk Factor

• Age is a primary risk factor for cardiovascular diseases.
• Heart failure incidence rises above 10% in individuals over 70 years old.
• The highest incidence of sudden cardiac arrest occurs in people over 60 years old.
• Sudden Cardiac Death is roughly 100-fold lower in persons under 30 years old.
• Cardiovascular system changes are divided into structural, functional and molecular changes in the heart and vasculature.

Structural Changes in Aged Cardiovascular Systems

• The normal heart anatomy includes SA node, AV node, Bundle of His, Left and right bundle branches and Purkinje fibres.
• Anatomical features of the heart include the systemic and coronary circulations, and the four chambers.
• The right side of the heart receives deoxygenated blood and pumps it to the lungs via the pulmonary circuit for oxygenation.
• The left side receives oxygenated blood and pumps it to all tissues through the systemic circuit.
• Two atria, two ventricles form the hearts four chambers, acting as two simultaneous pumps.
• Key events in the cardiac cycle include atrial systole, ventricular systole, and ventricular diastole.
• Histopathology features include the endocardium, myocardium, epicardium and the pericardium.
• The endocardium is a thin, smooth epithelial layer.
• The Myocardium the thickest layer, contracts to pump blood.
• The Epicardium is the thin and outer most layer of the heart wall.
• The pericardium is the sac that encloses the heart.
• Left ventricular hypertrophy can happen through increased wall thickness or enlargement of LV cavity.
• Atrial structure changes encompass atrial hypertrophy and dilation.
• valve structure is affected by fibrosis, collagen accumulation, and calcification.

Normal Vascular Anatomy

• Arteries and veins have three layers: tunica intima, tunica media, and tunica externa/adventitia,
• The tunica intima (inner most) contains endothelial cells around the lumen where blood flows.
• The tunica media (middle) contains smooth muscle and elastic fibres.
• The Tunica externa/adventitia (outer most) contains collagen and elastic fibres for stretch and flexibility.
• Capillaries facilitate exchange between blood and the body.

Aged Cardiovascular System

• General aging effects on arteries include arterial wall thickening, lumen dilation, and stiffness.
• Endothelial dysfunction occurs with reduced nitric oxide and decreased smooth muscle proliferation.
• Aortic stiffening occurs as elastic arteries lose elasticity, leading to higher systolic and lower diastolic blood pressure.
• Collagen accumulation and decreased elastin contribute to aortic stiffening.
• Vascular structure changes occur primarily in arteries closest to the heart, affecting proximal before distal systemic arteries, and left before right side.

Functional Changes in Aged Cardiovascular Systems

• Blood pressure regulation is affected by impaired baroreceptor-reflex function.
• Systolic blood pressure increases with age, while diastolic blood pressure decreases slowly.
• Systolic heart failure involves decreased myocardial contractility, maximum heart rate, and ejection fraction.
• Systolic heart failure is associated with reduced ejection fraction (HFrEF) and is measured by echocardiography.
• Diastolic heart failure involves decreased LV diastolic function with ventricle filling shifting to atrial contraction.
• Diastolic heart failure is associated with preserved ejection fraction (HFpEF) and is measured by echocardiography.
• HFrEF heart failure is has a reduced ejection fraction, at 40% of less.
• HFmrEF heart failure is mildly reduced ejection fraction, between 41-49%.
• HFpEF heart failure is preserved ejection fraction, at 50% or more.
• Coronary artery perfusion, primarily during diastole, is affected by increased systolic pressure raising myocardial oxygen demand.
• Electrical function declines with the reduction of pacemaker cells in the sinoatrial node (SAN).
• Electrical function declines with increased incidence of palpitation, dizziness and syncope.
• Remodeling of tissue in the AV node, bundle of His, and bundle branches leads to altered depolarization and repolarization.

Molecular Changes in Aged Cardiovascular System

• Cellular senescence, a hallmark of aging, involves irreversible cell cycle arrest and telomere shortening.
• Accumulation of senescent cells impairs heart function and promotes atherosclerosis.
• Mitochondrial function declines, with clonal expansion of dysfunctional mitochondria, increased reactive oxygen species (ROS), and mitophagy suppression.
• Calcium signaling is associated with mitochondrial dysfunction, including decreased activity/expression of sarcoplasmic reticulum Ca2+ ATPase (SERCA).
• There is reduced calcium sequestration in the sarcoplasmic reticulum and altered ryanodine receptor (RyR).
• Neurohormonal signaling is chronically activated, involving the renin-angiotensin-aldosterone system (RAAS) and β – adrenergic receptors.

Summary of Aging Effects on the Heart

• The aged heart can still supply blood adequately, but is less able to tolerate increased workloads in response to stressful situations.
• Aging cardiovascular system: shortness of breath, decreased quality of life, and heart failure.
• Structural changes include fibrosis and ventricular hypertrophy.
• Functional changes include ventricular/atrial dilation and impact electrical conduction and baroreceptor reflex.
• Molecular changes include cellular senescence, mitochondrial dysfunction, RAAS activation, and RyR dysfunction, with increased ROS.