Atherosclerosis Risk Factors Flashcards
Name 3 mechanisms by which smoking affects vascular biology
- Endothelial dysfunction:
* decrases NO, increases reactive oxygen species. Flow mediated dilation diminished. - Prothrombotic:
- increases thromboxane A2, decreases prostacyclin = platelet aggregation
- increases prothrombotic substances like vWF, thrombin and fibrin
- decreases antrithrombotic/fibrinolytic substances like tpa, plasminogen activator inhibitor-1
- Inflammation:
* increases leukocytes, IL-6, CRP, TNF-alpha, IL-1-B
What is the risk of heavy smokers (> 15 cigarettes a day) requiring an amputation after LE bypass compared with non-heavy smokers?
21% vs 2% at 3 years
Name 7 smoking cessation tools. Which is most effective?
- Varenicicline
- Buproprion
- Nicotine patch
- Nicotine gum
- Nicotine inhaler.
- Nicotine losenge
- Nicotine nasal spray
Varinecicline and nicotine patch most effective - abstinence 30-35%
What is the difference between type 1 and type 2 diabetes?
DM1 - Absolute deficiency of insulin secretion, 5-10% of diabetics, cellular mediated auto immune destruction of pancreatic beta cells
DM2 - combination of insulin resistance and inadequate compensatory insulin secretion - heterogeneous etiology
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Name 3 large trials that looked at the impact of tight glycemic control (<6.5 %) vs. standard (7-8%) on macrovascular parameters.
What were the findings?
ACCORD, ADVANCE, Veterans Affairs Diabetes Trial.
All failed to demonstrate a reduction in CV outcomes and in fact increased the CV mortality in the ACCORD trial that was stopped early. This is why the treatment recommendation is to target A1c of 7
DDP-4 inhibitors (e.g. sitagliptin)
- What is the mechanism of action
- Expected A1C reduction
- Mechanism of action: inhibit degradation of endogenous GLP-1 thereby enhanceing effect of incretins
- A1C Reduction: 0.6-0.8%
GLP-1 Mimetics (e.g. exenatide)
- What is the mechanism of action
- Expected A1C reduction
- Adverse effects
- Mechanism of action: increases glucose dependent insulin secretion, decrease glucagon, delay gastric emptying
- A1C Reduction: 1%
3 Adverse effects: nausea/vomit
Thiazolidinediones (e.g. rosiglitazone, pioglitazone)
- What is the mechanism of action
- Expected A1C reduction
- Adverse effects
- Mechanism of action: activates PPAR-gamma nucrease receptor which increases peripheral insulin sensitivity and reduces hepatic glucose production
- A1C Reduction: 1-1.5%
3 Adverse effects: weight gain, edema, possible bone loss in women
Alpha - glucosidase inhibitors (e.g. acarbose, miglitol)
- What is the mechanism of action
- Expected A1C reduction
- Adverse effects
- Outcomes/Safety concerns
- Mechanism of action: slows gut carbohydrate reabsorption
- A1C Reduction: 0.5 - 1%
3 Adverse effects: gas, bloating
- Outcome/Safety: Imporves postprandial glucose excursions which may improve CVD
Glinides Nateglinide
- What is the mechanism of action
- Expected A1C reduction
- Adverse effects
- Outcomes/Safety concerns
- Mechanism of action: Bind to sulfonylurea receptors on pancreatic ilset cells stimulating insulin release
- A1C Reduction: 1-2%
3 Adverse effects: Hypoglycemia, weight gain
- Outcome/Safety: Hypoglycemia may precipitate ischemia or arrythmia
Sulfonylureas (e.g. Gliclazide)
- What is the mechanism of action
- Expected A1C reduction
- Adverse effects
- Outcomes/Safety concerns
- Mechanism of action: Bind to sulfonylurea receptors on pancreatic ilset cells stimulating insulin release
- A1C Reduction: 1-2%
3 Adverse effects: Hypoglycemia, weight gain
- Outcome/Safety: Hypoglycemia may precipitate ischemia or arrythmia