Atherosclerosis Meds

Question 1

CHD risk factors

Answer 1

• age and gender
• lipoprotein disorders
• HTN
• DM
• fam history of premature CHD
• smoking

Question 2

In the general population, clinical atherosclerosis CVD is strongly related to age, in a gender dependent manner, increasing in the ______ in men and ______ in women.

Answer 2

• 40s in men; 50s in women

- women tend to have more events later in life and are less likely to survive the events

Question 3

4 lipid categories and their associated with atherosclerotic CV risk

Answer 3

• total and LDL-C: direct
• HDL-C: inverse
• TGs: direct
• Lpa: direct; genetic biomarker of risk

Question 4

Blood pressure and CVD risk

Answer 4

-linear, direct relationship; lower is better!

Question 5

DM and CHD

Answer 5

• diabetes is a heart disease “equivalent” because it confers as much risk of future CVD as existing heart disease without DM
• combination of DM and existing heart disease carries remarkable risk of future MI

Question 6

T/F: Genetics only play a role in early heart disease.

Answer 6

• false; family history of atherosclerotic heart disease, particularly early onset in 1st degree relatives is a major risk factor for future heart disease independent of other factors
• still genetics influencing events happening over the age of 65, but most telling at younger ages

Question 7

Traditional risk factors confer ______ risk of heart disease.

Answer 7

-additive

Question 8

4 patient groups that guidelines recommend high or moderate intensity statins for

Answer 8

1. clinical ASCVD
2. LDL-C >/ 190 mg/dL
3. DM
4. 10 year risk >/7.5% (meant to capture those with strong family histories)

Question 9

The fact that 30-40% of subjects with premature CHD are not considered high-risk tells us what?

Answer 9

• traditional risk factors do not identify all high-risk subjects
• there are still unknown risk factors we need to uncover!!

Question 10

Clinical identification of the metabolic syndrome

Answer 10

• abdominal obesity in men >102 cm, women >88 cm
• TGs >150
• HDL in men 130/>85
• fasting glucose >110 mg/dL
• 3/5= metabolic syndrome and high risk for CHD

Question 11

Why is it important to measure more than just LDL-C?

Answer 11

• TGs were shown to be an independent, atherogenic risk factor; and thus remnants carrying high TGs are also atherogenic and need to be measured
• basically, all non-HDL-C= atherogenic

Question 12

6 selective emerging risk factors for atherosclerosis

Answer 12

• Lpa
• homocysteine
• fibrinogen
• inflammatory markers
• subclinical atherosclerosis imaging
• genetic variation

Question 13

List 4 inflammatory markers looked at as markers of CVD risk

Answer 13

• CRP
• SAA
• siCAM-1
• IL-6
• they are not causal, but mark those at higher risk
• really on CRP is used clinically

Question 14

If someone is born with a gene that raises their CRP level, are they are heightening risk of CVD?

Answer 14

-no, they are not causal! just markers

Question 15

Methods for non-invasive imaging of atherosclerosis as a way to measure subclinical atherosclerosis

Answer 15

• B-mode ultrasound of carotids: intimal-medial thickness
• electron beam tomography of coronaries: look for coronary artery calcification; more Ca = more plaque= higher risk
• magnetic resonance imaging of aorta, carotids, coronaries: plaque size and morphology
• molecular imaging

Question 16

Why is screening for calcification especially beneficial?

Answer 16

-Ca in coronaries tends to detect events 10 years before they happen!; so check women in their 40s

Question 17

2 options for DNA variants that promote risk

Answer 17

1. gene may increase a risk factor which increases CAD OR

2. gene may directly influence MI without operative through risk factors

Question 18

GWAS studies >100,000 people have uncovered 95 lipid loci. Why is this so important?

Answer 18

• uncovers new targets!! like ADAMTS7

- 2/3 of them have no known connections to risk factors

Question 19

Potential role of ADAMTS7 in atherosclerosis

Answer 19

-activated ADAMTS7 turns SMCs into a synthetic phenotypes

Question 20

ADAMTS7 plays a role in atherosclerosis formation, while ______ is thought to maybe play a role in plaque rupture/thrombosis.

Answer 20

• ABO locus

- O seems to be protective bc no glycosylation occurs

Question 21

GWAS is importantly utilized in uncovering common variants conferring small effects. While ________ helps find the rare/mendelian variants conferring strong effects on risk.

Answer 21

• sequencing/exome sequencing
  ex: PCSK9, FH
• we now try to target PCSK9 with small mlc inhibitors, ASO