Lecture 17: Cardiac/Vascular risk factors

Question 1

what is the atherosclerosis?

Answer 1

Atherosclerosis (most common type of arteriosclerosis): multifactorial inflammatory disease of the intima, manifesting at points of hemodynamic shear stress

Question 2

endothelial dysfunction in early atherogenesis leads too…

Answer 2

–Invasion of inflammatory cells (mainly monocytes and lymphocytes) through the disrupted endothelial barrier
–Adhesion of platelets to the damaged vessel wall → platelets release inflammatory mediators (e.g., cytokines) and platelet-derived growth factor (PDGF)
–PDGF stimulates migration and proliferation of smooth muscle cells (SMC) in the tunica intima and mediates differentiation of fibroblasts into myofibroblasts
Inflammation of the vessel wall

Question 3

what causes chronic stress on endothelium?

Answer 3

arterial hypertension and turbulence

Question 4

what substance causes migration of smooth muscle cells into tunic intima?

Answer 4

PDGF

Question 5

how fatty streaks are formed (early atherosclerotic lesion)

Answer 5

• -inflammation of the vessel wall
• -LDL enters through the damaged vessel wall, accumulates, and is oxidized by free radicals.
• -Macrophages and SMCs ingest cholesterol from oxidized LDL and transform into foam cells.
• -Foam cells accumulate to form fatty streaks (early atherosclerotic lesions).

Question 6

how fibrous plaques are formed?

Answer 6

• -lipid-laden macrophages and SMCs produce extracellular matrix (e.g., collagen) → development of a fibrous plaque (atheroma)
• -Macrophages, smooth muscle cells, lymphocytes and extracellular matrix form a fibrous cap, which covers a necrotic center, consisting of foam cells, free cholesterol crystals, and cellular debris.

Question 7

why? fibrous plaque is ruptured?

Answer 7

• -inlammatory cells in the atheroma (e.g., macrophages) secrete matrix metalloproteinases → weakening of the fibrous cap of the plaque due to the breakdown of extracellular matrix → minor stress ruptures the fibrous cap
• -Plaque rupture → exposure of thrombogenic material (e.g., collagen) → thrombus formation with vascular occlusion or spreading of thrombogenic material

Question 8

what are the manifestations of atherosclerosis?

Answer 8

• -Coronary Heart Disease (CHD), manifested by myocardial infarction (MI), angina pectoris, heart failure, and coronary death
• -CerebroVascular Disease (CVD), manifested by stroke and transient ischaemic attack
• -Peripheral Artery (or Vascular) Disease (PAD or PVD), manifested by intermittent claudication
• -Aortic Atherosclerosis and thoracic or abdominal aortic aneurysm (AAA)
• -Vascular Diseases of the Kidney – renal artery stenosis and/or ischaemic nephropathy

Question 9

what is the epidemiology of cardiovascular diseases?

Answer 9

• -In 2012, CVD was estimated to result in 17.3 million deaths worldwide.
• -By 2030 more than 23 million people will die annually from CVDs (WHO estimate).
• -Most common cause of death in Ireland.
• -Accounts for 36% of all deaths.
• -Approximately, 10,000 people die in Ireland from cardiovascular disease.
• -Also a major cause of disability worldwide.

Question 10

primary vs secondary prevention?

Answer 10

• -Primary prevention: Avoid occurrence of disease

- -Secondary prevention: Reduce risk of recurrence and retard progression of existing disease

Question 11

what is primary prevention?

Answer 11

• -Prevent the onset of specific diseases via risk reduction by altering behaviors or exposures that can lead to disease, or by enhancing resistance to the effects of exposure to a disease agent.
• -Primarily decrease the incidence, and in turn, decrease the prevalence of disease.

Question 12

examples of primary prevention?

Answer 12

• -Immunization
• -Lifestyle modification ( smoking cessation, eating habits, dental care)
• -Fortification of salt with iodine to prevent iodine deficiency
• -Fluoridation of toothpaste, water, and salt to reduce the risk of dental caries
• -Fortification of food with folic acid to reduce the prevalence of neural tube defects
• -Health legislation ( smoking cessation, eating habits, dental care)

Question 13

what is secondary prevention??

Answer 13

• -Early detection of disease in asymptomatic patients to promote early intervention, and to prevent further progression and complications from the disease.
• -Consists of a 2-step process: screening test to identify the disease and a follow-up for management of the disease.
• -Secondary prevention testing measures are not intended to be diagnostic!

Question 14

screening is an example of primary or secondary prevention?

Answer 14

secondary

Question 15

examples of secondary prevention?

Answer 15

• -General medical examination (“checkup”): blood pressure measurement for hypertension
• -Laboratory testing (lipid panel, HIV, etc.)
• -Other screening tests ( colonoscopy, mammography, etc.)

Question 16

what are the non-modifiable risk factors of CVDs?

Answer 16

• -Age
• -Gender
• -Family History (Genetics)
• -Race
• -Personal History

Question 17

what are the modifiable risk factors of CVDs?

Answer 17

• -Smoking
• -Hypertension
• -Cholesterol
• -Diabetes
• -Obesity / Diet Quantity (Calories)
• -Diet Quality
  1) Excesses: Salt, Sugar, Excess Fats
  2) Deficiencies: Fruits, Vegetables, Omega-3 Fats
• -Lack of Fitness
• -Renal Dysfunction/Failure
• -Psychosocial factors
• -Alcohol

Question 18

what is the most important factor in lowering the risk for CVs?

Answer 18

• -Risk of recurrent MI in patients who have had an MI falls by 50% within one year of smoking cessation
• -Benefits are seen regardless of how long and how much the patient smoked

Question 19

Pulse pressure is the best predictor of CVD in all age groups. True/False

Answer 19

False

• -With increasing age, there was a gradual shift from DBP to SBP and then to PP as predictors of CHD risk”.
• -Age <50 years; DBP best
• -Age 50-59 years; DBP = SBP = PP
• -Age > 60 years; PP best

Question 20

what is the most common cause of death in DM?

Answer 20

CVD

• -People with type 2 diabetes die 5-10 years before people without diabetes and most of this excess mortality is due to cardiovascular disease
• -High blood glucose and glycosylated haemoglobin levels also correlated with increased cardiovascular risk

Question 21

how exercise protects against CVD?

Answer 21

• -Result from the benefits of exercise in
• -reducing blood pressure
• -controlling blood cholesterol levels
• -improving glucose control in diabetes
• -weight reduction

Question 22

how much exercise is recommended to prevent CVDs?

Answer 22

• -30 minutes of brisk activity on
• -most preferably every day of the week at
• -50-75 percent of maximum heart rate.

Question 23

does obesity increase the risk of CVD?

Answer 23

• -Associated with other risk factors (Particularly Hypertension, Dyslipidaemia & Diabetes)
• -Also independently predicts occurrence of CHD and stroke

Question 24

what are the effects of weight loss on plasm lipid levels?

Answer 24

During active weight loss, serum HDL-cholesterol concentrations decrease, but later increase once weight loss stabilizes. The greatest improvements in serum lipid concentrations tend to occur in the first 4 to 8 weeks of weight loss. The degree of improvement in triglyceride and cholesterol concentrations is related to the amount of weight lost, and weight regain leads to relapse in serum lipid levels. At 2 years, a sustained weight loss of 5% is sufficient to maintain the reduction in serum triglyceride concentrations, whereas serum total and LDL-cholesterol revert toward baseline unless a 10% weight loss is maintained

Question 25

what are the other risk factors of CVD?

Answer 25

- -Alcohol - lack of moderate alcohol intake may be a risk factor - -Psychosocial factors - may contribute to development of atherosclerosis as well as acute MI and cardiac death - -Chronic kidney disease - associated with increased risk of CHD; leading cause of death in patients with CKD is cardiovascular disease. - -Inflammatory markers – raised CRP has been associated with increased risk but role in uncertain - -HIV – higher rates of CHD in HIV+ patients compared with HIV- controls even after correction for traditional risk factors - -Infection – possible role

Question 26

what is the risk factor clustering?

Answer 26

- -Diabetics very likely to be hypertensive, obese and dyslipidaemic which contributes to the vascular risk burden. - -Patients with hypertension very likely to have other risk factors.

Question 27

what factor increases the risk of CVDs in diabetics?

Answer 27

The presence of hypertension further increases the already high risk of cardiovascular (CV) disease associated with type 2 diabetes. There is an approximate 2-fold increased risk of CV disease in hypertensive vs. normotensive patients with diabetes; similarly, patients with diabetes have a 2-fold increased risk for CV disease than patients without diabetes. The combination of diabetes and hypertension gives an approximate 4-fold increase in CV risk over the nondiabetic, normotensive population.

Question 28

what are the measures of primordial prevention- whole population reduction of risk factor levels?

Answer 28

1) Every adult should know their numbers - -BP < 140/90 - -total Cholesterol < 5.0 mmol/l - -LDL Cholesterol < 3.0 mmol/l - -HDL Cholesterol > 1.0 mmol/l - -Fasting Glucose < 6.5 mmol/l 2) Smoking - -Taxation - -Smoking in work-place/enclosed spaces ban - -Plain labeling with prominent warnings 3) Healthy diet to be promoted - -Labelling of constituents - -Taxation policy - -School provision of fruit - -Ban on junk food advertising to children - -Targets for salt reduction in processed foods. 4) Exercise facilitation - -School programs - -Provision of walkways -Sli na Slainte

Question 29

what lifestyle changes should be performed to reduce the risk of CVDs?

Answer 29

1) Stop smoking 2) Diet - -Reduce calories, saturated fat, and salt - -Reduce packaged, processed and take-aways - -Increase fish, fruit, and vegetables 3) Alcohol in moderation - -<17 units/week males and <11units/week for females 4) Regular exercise

Question 30

what are the antiplatelet drugs used for primary/secondary prevention of CVD?

Answer 30

- -Aspirin | - -Clopidogrel

Question 31

what are the lipid-lowering drugs used for primary/secondary prevention of CVD?

Answer 31

- -Statins - -Fibrates - -Cholesterol absorption inhibitors - -PCSK9 inhibitors

Question 32

what are the BP-lowering drugs used for primary/secondary prevention of CVD?

Answer 32

ACE-Inhibitors/ARBs Calcium-channel blockers Diuretics

Question 33

what are the hypoglycemics drugs used for primary/secondary prevention of CVD?

Answer 33

- -Biguanides - -Sulphonylureas - -Glitazones - -Acarbose - -Insulin

Question 34

what are the anti-obesity drugs used for primary/secondary prevention of CVD?

Answer 34

- -Orlistat | - -Sibutramine

Question 35

what is metabolic syndrome?

Answer 35

A constellation of medical conditions that increase the risk for cardiovascular disease, type 2 diabetes mellitus, and fatty liver. Presence of ≥ 3 of the following conditions (or already receiving medical treatment for them): - -Insulin resistance: fasting glucose ≥ 100 mg/dL - -Elevated blood pressure: ≥ 130/85 mm Hg - -Elevated triglycerides: ≥ 150 mg/dL - -Low HDL-C: in men < 40 mg/dL; in women < 50 mg/dL - -Abdominal obesity: waist circumference ≥ 102 cm in men; ≥ 88 cm in women

Question 36

what type of obesity particularly increases the risk of CVD?

Answer 36

Abdominal obesity Whereas obesity in general is a known risk factor for many diseases, the accumulation of fat in visceral tissue (abdominal obesity) has been particularly associated with an atherogenic and hyperglycemic state.