Chemical Pathology - Lipid update

Question 1

what did the SPRINT study find about mpdulating blood pressure?

Answer 1

aggressive management of BP and lipids improves survival

Question 2

what is the optimal medical therapy in people with CHD?

Answer 2

• intensive lifestyle modification
• high dose statin (atorvastatin 40-80mg OD
• assessment for probably T2DM (HbA1c)
• aspirin
• optimal BP control

Question 3

what are the options for statin intolerant patients?

Answer 3

• ezetemibe (reduced absorption - block NPC1L1)
• plasma exchange
• Evolocumab (PCSK9 monoclonal antibody)

Question 4

what does the PCSK9 antibody do?

Answer 4

• regulates levels of LDL-receptor expression

- if you inhibit PCSK9 = high LDL-R on liver = low plasma LDL

Question 5

what did the FOURIER “PCSK9” study show?

Answer 5

PCSK9 inhibition reduced major CVS events
effect on mortality was insignficant
NNT was high

Question 6

how can this be linked to clinical practice?

Answer 6

reserve for high risk patients

• statin intolerant
• uncontrolled lipids (i.e. FH)

Question 7

how many years of good glucose control in newly diagnosed T2DM patients is needed before you see the benefits in health?

Answer 7

15 years

Question 8

what is the legacy effect?

Answer 8

having good blood glucose control, even for short while, can improve later mortality

Question 9

what did the DCCT study show?

Answer 9

T1DM

good control improves outcome and legacy effect

Question 10

what did the UKPDS study show?

Answer 10

T2DM

good control improves outcome and legacy effect

Question 11

what did the ACCORD study show?

Answer 11

suddenly aggressively controlling the blood glucose of people who had poor control for decades = reduced complications but increased mortality

Question 12

how do SGLT2 inhibitors work?

Answer 12

reduced glucose re-uptake in kidneys
osmotic diuresis (reduced blood glucose and low BP)
e.g. empagliflozin

Question 13

What did the EMPA-RED study show?

Answer 13

Study in empagliflozin
significant reduction in mortality and incidence of CV events after just 4 years
quick reduction
other areas of treatment: treat HF (diuresis), prevent neuropathy

Question 14

what does GLP-1 do?

Answer 14

• secreted from gut L-cells
• signals to pancreas to make insulin
• direct effect on appetite and gastric emptying
• incretin effect

Question 15

what breaks down GLP-1?

Answer 15

broken down by DPP4

inhibiting DPP4 using Gliptins makes GLP01 last longer e.g. sitagliptin

Question 16

name some GLP-1 analogues

Answer 16

• exenatide
• liraglutide
• semaglutide

Question 17

what is the best medical management of T2DM?

Answer 17

1. Metformin

2. Dual therapy: add on either SGLT-2 or GLP-1 analogues