Cardiovascular Disease: Risk Factors, Regulation, and Treatment

Posted on May 6, 2024 in Biology

1. Risk Factors for Atherosclerosis

Metabolic

Other

  • High Blood Pressure (HBP)
  • Central Obesity
  • Hyperinsulinemia
  • Diabetes Mellitus (DM)
  • Hypercoagulation
  • Dyslipidemia
  • Hyperlipoproteinemia
  • Increased Prothrombotic Factors
  • Increased Proinflammatory Factors
  • Smoking
  • Age, Male Gender

2. Acute Phase Proteins and Their Role in CVD Diagnosis

Type & Function

  • Fibrinogen (Increased Coagulation, Local Thrombus Formation, Decreased Microbe Spread)
  • A1-Antitrypsin (Counters Local Proteases, Decreased Tissue Destruction)
  • C-Reactive Protein (CRP) (Opsonization of Pathogens, Phagocytosis, Complement Activation)
  • Haptoglobin (Binds to Hemoglobin, Decreased Renal Excretion and Strain)
  • Ceruloplasmin (Decreased Free Radical Formation)
  • C3 Complement (Opsonization & Chemotaxis)
  • Ferritin (Removes Fe2+, Decreased Pathogen Growth)
  • Hepcidin (Decreased Ferroportin, Decreased Fe2+ Absorption)
  • Thrombopoietin (Increased Megakaryopoiesis, Increased Thrombocytes)

3. Regulation of Arterial Blood Pressure

Local Regulation

Systemic Regulation

  • Myogenic Factors:

    Mechanical Stretching -> Contraction

  • Metabolites:

    H+, K+, ADP -> Dilation

  • Endothelial-Derived Factors:

    NO, PGI2 -> Dilation

  • Nervous System:

    • Baroreceptor Reflex
    • Cardiopulmonary Reflex

  • Endocrine System:

    • Catecholamines
    • Renin-Angiotensin-Aldosterone System (RAAS)
    • Vasopressin
    • Atriopeptin

4. Molecular Basis of Drugs Affecting High Blood Pressure

Drugs Inducing High Blood Pressure:

Effect

  • Direct-Acting Norepinephrine (NE) Agonists:
    Bind to A + B receptors -> Sympathetic-like effects (NE release)
  • Indirect-Acting NE Agonists:
    Block NE uptake, Increase NE release
  • Oral Contraceptives:
    Estrogen activates RAAS
  • Nonsteroidal Anti-inflammatory Drugs (NSAIDs):
    Decrease Prostaglandin (PG) synthesis -> Decreased Vasodilation
  • Exogenous Glucocorticoids/Mineralocorticoids:
    Same as endogenous hormones
  • Erythropoietin:
    Increased Red Blood Cell (RBC) production -> Increased blood viscosity

Drugs Treating High Blood Pressure:

Effect

  • Diuretics:
    Decreased Renal Water + Electrolytes -> Decreased Blood Volume (BV)
  • Beta-Blockers:
    Decreased Cardiac Output (CO), Renin, Sympathetic Outflow
  • Alpha-Blockers:
    Decreased Peripheral Vascular Resistance (R)
  • Clonidine:
    A2-Agonist -> Decreased NE Outflow
  • Angiotensin-Converting Enzyme (ACE) Inhibitors:
    Decreased Conversion of Angiotensin I to II, Increased Bradykinin
  • Angiotensin II Receptor Blockers (ARBs):
    Block Receptors -> Decreased Action of Angiotensin II
  • Calcium Channel Blockers (CCBs):
    Block Ca2+ Receptors -> Decreased Ca2+ Inflow -> Decreased Smooth Muscle Cell (SMC) Contraction
  • Nitrates:
    Decreased Coronary Vasoconstriction, Decreased Cardiac Preload

5. Peculiarities of Heart Muscle Structure & Metabolism

The heart consists of cardiac muscle cells and specialized conduction fibers. Atrial and ventricular cells form two syncytia with tightly interconnected cells, allowing excitation of one cell to activate surrounding cells. The two syncytia are separated by a fibrous ring to prevent uncontrolled conduction. Cardiac muscle cells are separated by intercalated discs with gap junctions for free ion diffusion. Conduction cells contract weakly due to fewer contractile fibers. The AV bundle enables electrical conduction from atria to ventricles with a physiological delay in the AV node. Cardiac muscle, unlike skeletal muscle, cannot rest and relies almost entirely on aerobic metabolism, primarily using free fatty acids (FFAs) and lactate. High mitochondria and myoglobin levels support this metabolic demand.

6. Markers of Myocardial Infarction (MI)

Cardiac markers include cardiac enzymes (CPK-MB), cell content (Troponin I and T), total CK, and myoglobin. Total CK and CK-MB rise several hours after MI and peak at 24 hours. Troponin I and T are highly sensitive and specific for MI, detectable 3-6 hours after MI and remaining elevated for 10-14 days. Myoglobin is detectable earlier than CK-MB and troponin (within 2 hours) but is not cardiac-specific. LDH levels rise more gradually, peaking 3-5 days after the event.

7. Endocrine System Regulation of Blood Pressure

The kidneys play a crucial role in blood pressure regulation through the renin-angiotensin-aldosterone system (RAAS), vasopressin, erythropoietin, and other hormones. RAAS increases blood pressure through angiotensin II and aldosterone, which promotes sodium and water reabsorption. Vasopressin from the hypothalamus increases water reabsorption, blood volume, and peripheral resistance. Erythropoietin stimulates the adrenal medulla to release norepinephrine, causing vasoconstriction. ACTH from the pituitary gland stimulates cortisol and aldosterone secretion, further influencing sodium and water reabsorption. Cortisol also promotes sodium and potassium reabsorption. Catecholamines from the adrenal glands increase peripheral vascular resistance.

8. Main Lipids of Blood Plasma and Their Functions

Blood plasma contains various lipids with diverse functions. Fatty acids serve as energy sources, structural components of membranes, and precursors for hormone-like prostaglandins. Triglycerides (TAGs) are stored in adipose tissue as energy reserves. Cholesterol esters are essential for cell membranes, bile acid production, steroid hormones, and vitamin D synthesis. Phospholipids, with their amphipathic nature, contribute to membrane structure and function as intracellular messengers. Plasma lipoproteins, including chylomicrons, VLDL, IDL, LDL, and HDL, transport lipids in the blood and differ in size, composition, and density.

9. Apolipoproteins and Their Functions

Apolipoproteins are protein components of lipoproteins with multiple functions, including lipid transport facilitation, enzyme activation (LCAT, LPL, HTGL), cell surface receptor binding, and structural roles. ApoB is used to estimate LDL levels and cardiovascular risk, while ApoA, the major apolipoprotein of HDL, is linked with reduced CVD risk.

10. Dyslipidemias and Their Treatment

Dyslipidemias, characterized by abnormal blood lipid levels, are major risk factors for coronary heart disease (CHD). Treatment goals include decreasing LDL, VLDL, chylomicrons, and increasing HDL. Therapeutic approaches target lipoprotein production, degradation, cholesterol absorption, and removal. Statins inhibit HMG-CoA reductase, reducing cholesterol synthesis. Niacin decreases lipolysis and VLDL production. Fibrates activate PPARs, regulating gene expression related to lipoprotein structure and function. Bile acid sequestrants lower bile acid concentration, promoting cholesterol conversion and LDL uptake. Cholesterol absorption inhibitors reduce intestinal cholesterol absorption. Combined therapy using multiple drugs can achieve optimal lipid levels.

11. Antioxidative Systems and CVD

Oxidative stress, characterized by increased reactive oxygen species (ROS), can damage cells and contribute to CVD. Protective mechanisms include enzymes like SOD, glutathione peroxidase, and catalase, as well as antioxidants like glutathione and vitamins C and E. Oxidative stress plays a significant role in atherosclerosis development, leading to CVD.