Flashcards in Cardiology Risk Factors Deck (40)
What type of cells maintain the integrity and elasticity of arterial vasculature
Endothelial cells and smooth muscle cells.
Characteristics of endothelial cells
Impermeable to large molecules (LCL-C)
Characteristics of smooth muscle cells
Control vascular tone
Produce extracellular matrix that maintains vascular integrity.
Within the arterial medial layer.
Hallmark of early atherogenesis and its result
Endothelial cell dysfunction -- this allows lipoproteins (LCL) into subintimal space.
Progression of early atherogenesis
Immunologic recruitment (t-cells, monocytes)
LDL modification -- glycation/oxidation stimulates inflammation
Uptake of mLDL by monocytes to create foam cells
Cellular apoptosis and lesion formation
Progression of plaque formation
Smooth muscle cell migration initiated by foam cells and endothelial cells.
Smooth muscle cell proliferation and secretion of ECM (collagen) to create fibrous cap.
What type of remodeling is done in early vs late plaque formation.
Early plaque formation is characterized by outward remodeling, which preserves luminal diameter.
Late plaque formation restricts vessel lumen and causes ischemic symptoms.
Stable and vulnerable phenotype development
Phenotype determined by the balance between cap degradation and cap synthesis.
An enzyme that degrades the fibrous cap and inhibits matrix synthesis. Stimulated by inflammatory cytokines.
Characteristics of a vulnerable plaque
Large lipid cores, thin fibrous cap, many inflammatory cells.
Characteristics of a stable plaque
Small lipid pool, thick fibrous cap, preserved arterial lumen.
Process of plaque disruption
Fibrous cap rupture (due to hemodynamic stress and matrix degradation)
Subsequent development of superimposed thrombus (that contains fibrin, RBC and platelets)
Clinical manifestation depends on vascular territory and stability of thrombus.
Current paradigm of atherosclerosis
A systemic disease that manifests locally.
Risk factors for atherosclerosis
Nonmodifiable (Age, Sex, Family History)
Modifiable (Dyslipidemia, smoking, DM, physical inactivity, hypertension)
Nontraditional (apolipoprotein a, C reactive protein, homocysteine)
Most males with CHD have how many risk factors?
CVD and age
Increases linearly with age
CVD and sex
Males more common early, women more common over 60
Function of lipoproteins
Transport cholesterol in the serum
Comprised of outer hydrophilic layer of proteins, phospholipids, cholesterol.
Inner layer has cholesteryl esters, and triglycerides
How does density of lipoproteins increase?
With more proteins
Reverse cholesterol transport
Scavenger delivering cholesterol from periphery to liver
Removes cholesterol from macrophages
Deposits in arterial wall leading to atherosclerosis
Primary goal of pharmacotherapy.
How to lower LDL-C?
Niacin, bile acid sequestrants, fibric acid.
HMG-CoA reductase inhibitors
How do HMG-CoA reductase inhibitors work?
They increase the LDL-C receptor expression in liver and lower serum levels of LDL-C. Also stop liver synthesis of cholesterol
Are statins effective? How?
Lower LDL-C, some elevation of HDL-C, reduce lipid content of the atherosclerotic plaque.
Also modulate vascular tone, stabilize plaques, reduce inflammation
Is increasing HDL-C favorable for decreasing CV events?
Hasn't proven useful yet
Cardiovascular effects of Dm
Enhanced inflammation, increased platelet reactivity and hypercoagulability, endothelial dysfunction, vascular stiffness
Essentially, accelerated atherosclerosis and a prothrombotic state.
Does DM affect CHD mortality?
Yes, increases it at least 2 fold.
Why is DM a CHD risk equivalent?
Because risk for coronary heart disease with DM and no prior MI is equal to those without DM with prior MI.
What are the treatment objectives in the diabetic patient?
Preventing microvascular complications (retinopathy, neuropathy, nephropathy)
Preventing macrovascular complications (stroke, MI, peripheral artery disease)
How are diabetics treated to prevent the things above?
Aggressive control of modifiable risk factors like BP, lipids, obesity.
**NOTE, glycemic control may reduce macrovascular risk, but jury is out**
Vascular effects of obesity/physical inactivity
Inflammation caused by adipose tissue secreting pro-inflammatory cytokines.
Hypertension -- increased cardiac output to meet the higher metabolic demands of excess body weight, along with changes in vascular tone.
Definition of obesity?
Guidelines for activity
30 minutes or more of moderate intensity physical activity on most days of the week.
Smoking is a CHD risk factor for young adults because...?
It increases fatty streaks and raised lesions in abdominal aorta in people 15-34.
Mechanism of smoking related injury
Prothombotic effects on platelets
Oxidative modification of LDL-C.
Is LDL-C sufficient alone as a risk factor?
No, think about Tim russert.
Role of homocysteine in atherogenesis
CVD patients have elevated levels of plasma homocysteine. May cause oxidative stress, inflammation, platelet aggregations. But reducing homocysteine doesn't have benefit on CV risk.
Lipoprotein A and CV risk
variant of LDL, may impair endogenous thrombolysis.
High LpA levels have higher risk