LIPIDS Flashcards
1
Q
Population of Europe 2016 roughly
A
0.7 billion
2
Q
Population of US roughly 2016
A
0.3 billion
3
Q
Population in low income countries roughly 2016
A
0.6 billion
4
Q
Population in high income countries 2016 roughly
A
1.2 billion
5
Q
Total no of deaths worldwide 2016 roughly
A
Near 60 million
6
Q
Percentage and number of deaths due to cardiovascular disease worldwide
A
30% and 17.5 million in 2015-16 . In US also 30%, but in Europe nearly 50% . I don’t know the reason
7
Q
Most common types of cardiovascular disease
A
80% heart attack and strokes
8
Q
_______% of reduction seen in CVD is due to change in risk factors and ______% due to improved treatment.
A
50 & 40
9
Q
SCORE system is not required for assessing risk in
A
- CVD
- Diabetes
- CKD
10
Q
SCORE estimates
A
First FATAL Heart attack, stroke, other occlusive arterial disease, SCD
11
Q
How to convert SCORE risk estimate to total CVD event risk
A
Multiply with 3 for males
With 4 for females
Lower in older persons
12
Q
Most frequent monogenic disorder a/w premature CVD
A
Familial hypercholesterolemia
13
Q
——is technically not fat
A
Cholesterol = steroid plus alcohol
14
Q
Incidence of DM with statins
A
1in 500
15
Q
SGPT and statins
A
> 3 times change or reduce
16
Q
CPK and statins
A
> 10 times stop??
17
Q
Statins for Diabetes at less than 40 yrs
A
Consider if multiple risk factors
18
Q
Role of statins in pregnancy
A
CONTRA INDICATED
19
Q
Why statins not used for primary prevention in young age 20s& 30s
A
- SAFETY of statins over decades of therapy uncertain .
- Also uncertain whether long term treatment leads to better OUTCOMES compared with postponing treatment until CV risk rises to an absolute level where treatment becomes warranted .
20
Q
Mobile and precautions of PPI
A
- Don’t keep on same side pocket
- Keep on opposite ear
- May be keep 15-20 cm away from PG
21
Q
Bile salts are made from
A
Cholesterol
22
Q
—-% of bile acids are re absorbed
A
95% by enterohepatic circulation
23
Q
Indications for statin treatment in children with hyperlipidemia
A
LDL above 190 and AGE 8 yrs or above not controlled with diet
24
Q
Incidence of FH-hetero and homo
A
Heterozygous 1:200-500
Homo-1: 1 million
25
3 conditions where statin treatment is considered as secondary prevention (other than CAD &stoke)
1. Peripheral arterial disease
2. Multiple risk factors that confer a 10-year risk of CVD >20%
3. Chronic kidney disease with estimated GFR <45 mL/min per 1.73 m2*
26
Effect of diet on LDL Cholesterol
In occasional patients with poor baseline diets, marked dietary change can lower LDL-C by as much as 30 percent
Otherwise around 5_7%
27
Framingham is a place in
Northeastern US
28
Why statins are given at night
The majority of cholesterol synthesis appears to occur at night
29
Criteria for FH Diagnosis-3 types
1. Dutch lipid clinical network criteria - commonly used
2. Simon Broom register criteria
3. WHO criteria
30
Total cholesterol level beyond which FH is to be suspected
310
31
Gall stones are an indication to stop treatment with..........
Fenofibrate
32
USPSTF 2016 recommendations for primary prevention with statins
```
ASCVD risk more than 10 % and at least one risk factor::
(Age40-75)
Risk factors
1. Dyslipidemia-LDL > 130; or HDL <40
2.DM
3.HTN
4.Smoking
```
NOT FOR LDL>190 or FH
33
NNT to prevent one major adverse CV event or death with statin primary prevention
50-200
34
Total cholesterol level in Homozygous FH
More than 500
35
Homozygous FH patients develop ----- before 20
CAD and Aortic stenosis before 20 and die before 30
36
Lomitapide is
Microsomal Triglyceride Transfer Protein
37
If left untreated Heterozygous FH will develop CAD before
55/60- males/ females
38
Frequency of Heterozygous FH
1/500 to 1/200
Around 14-34 million estimated pts worldwide
39
The risk of CHD in definite or probable Heterozygous FH
At least 10 fold
40
Incidence of FCH( familial combined hyperlipidemia)
1:100
41
Useful criteria for diagnosis of FCH
Apo B > 120 +TG>133 +family h/o of premature CAD
42
LDL particle number starts increasing when TG is more than
133 i.e. 1.5 mmol/l
43
SCORE risk assessment is for people without
DM,CKD, or FH
44
Name a bile acid sequestrant
ColeSEVelam
45
Role of statins in NAFLD/NASH
Statins are safe and may help Resolution of liver disease
Reduces ASCVD more than in people with normal liver function
46
Risk of new onset DM with moderate intensity statins
1 per 1000 pt years
47
Incidence of permanent liver damage with statins
1 in 2 million treated subjects
48
Moderate intensity statins should be able to reduce LDL cholesterol by
>30-<50%
High intensity 50% or more
49
Effect of statins on HDL
5-15% increase
50
Effect of Alcohol consumption in South asians in INTERHEART study
No protective effec
51
INTERHEART study population
Acute MI patients in 52 countries- case control study
52
Atherogenic dyslipidemia of South Asians
High TG + Low HDL
But total cholesterol and LDL are lower than western popln
53
CKD Stage 3 b is
GFR- 30-44 ml/mt
Stg 3A is 45-59ml/mt
54
Ankle brachial index of --- is considered as ASCVD
<0.9
55
Coronary artery calcium score more than----puts pt at high risk of coronary disease
300 or more (above 100 is moderate risk)
Also non stenotic carotid plaque
Lp(a) 50 or more (Above 20 moderate risk)
Indian guidelines
56
When to start statins in Diabetes
Age of 40yrs
Or if DMof > 15 yrs and Age of 30 yrs
57
Documented CAD by angiography means
>10% stenosis
Canadian lipid guidelines
58
If triglycerides more than ------don't use friedwald formula
400
59
Apo B is equivalent of
Non HDL cholesterol
60
Even direct assessment of HDL or LDL is accurate only if
TG is normal
61
Seasons and cholesterol
TC and HDL high during winter
62
CVD risk assessment is not required if TC is
More than 290 or inFH
63
Non HDL Cholesterol =
Total number of atherogenic lipoproteins in plasma
64
Lipoprotein (a) is
LDL + apoprotein(a)
65
Effect of high TG on Sodium
Pseudohyponatremia
66
Apo lipoprotein assay and fasting
Not required
67
If u suspect if high concentration of small dense ldl is suspected
Do Apolipoprotein B assay
68
Apo C III is
A new Cardiac risk factor
69
Role of Apo B in risk prediction
Apo B= LDL=Non HDL cholesterol
70
Apo A level corresponding to low HDL
Less than 120 ms/dl and 140 males and females respectively
71
Effect of high TG on HDL and LDL
Decrease HDL and increase SMALL DENSE LDL
72
External manifestations of FH
Xanthoma, Xanthelema, Arcus cornealis before 45
73
How to do CVD risk scoring in CKD
No risk scoring required
74
Treatment principles of high LDL
If low risk- treat if LDL > 190
High risk category treat LDL >100
Very high risk category treat if LDL > 70
75
Markers of sub clinical atherosclerotic vascular damage
ABI, Coronary Artery calcfn,Carotid USG
76
CPK and stopping statins
>10 times-STOP
Plenty of water
Weaker statins-Fluva/Prava after CK is normal
77
Statins dose and muscle toxicity
PRIMARILY at high doses
78
Cholesterol has the structure of ---
Steroid
| It is called a STEROL as it is Steroid plus AlcohOL
79
Pseudo hypertriglyceridemia is seen in
Hyperglycerolemia. The methods used estimate glycerol and triglycerides
80
Treatment goal in familial hypercholestrolemia
LDL <100 or less than 50% of original value ( for HeFH)
For Homozygous FH LDL<150 is the target
81
Incidence of FH
1 in 250 Heterozygous
| 1 in 1 million Homozygous
82
Difference between criteria for FH Homozygous and Heterozygous
Homozygous- LDL>500 or treated LDL>300 with clinical criteria
Heterozygous- Simon Broom or Dutch Lipid clinic criteria
83
Total number of FH patients in world
10 million
of these 7000 pts will be Homozygous😏 ( 1in 1 million incidence; total world popln of 7 billion)
So majority HeFH.
85% of males and 50% of these females will develop ASCVD before 65 yrs if proper care not taken
84
Cholesterol levels in pregnancy
Increase by 25-50%.
B/w 18-36 wks of pregnancy
85
Only cholesterol medicines permitted in pregnancy
Also lactation
Bile acid Sequestrants.
Not absorbed into blood
Reduce LDL by 15%
86
LDL apheresis during pregnancy frequency..
Weekly or biweekly
87
FH is suspected when LDL is above ....... in adults and above.... in children
190/ 160
88
Cascade screening means
Testing the family members for same illness
89
PCSK9 inhibitors work by
Preventing LDL Receptor degradation inside liver cells thus increasing LDL Receptors on liver surface
So more and more LDL from extra cellular fluid is removed
90
Patients with FH has a ....times higher risk of heart disease
20 times
FH foundation
91
In HeFH , the time by which pts develop heart disease
50% by 50 yrs males
30% by 60 yrs in females
92
Effect of cetp inhibitors on cardiac risk
Cetrapibs - Neutral or Negative
93
1% reduction in LDL reduces CAD risk by
1%
94
Statin studies in ACS population
MIRACL,PROVE IT,A-Z,IMPROVE IT
95
LDL Goal in high risk patients-American guidelines
1988 ATP 1
1993 ATP 2
2001ATP 3
2004ATP 3 update
2006 AHA ACC update
1988-130 less than FRAMINGHAM
1993-100 equal to or less than
2001- 100 less than
2004- 70 optional - less than ( HPS, PROVE IT, ASCOT LLA,PROSPER, ALLHAT LLT)
2006- reasonable (TNT,IDEAL)
96
Change Lipid guidelines in 2013 and 2016
2013- ACC AHA removed targets
2016- ESC- came back to Lower the better slogan
Also new entry of 50% or more reduction from baseline in very high and high risk subsets
Primary target in moderate and low risk is <115
97
Serum levels of LDL is predominantly controlled by ....
Hepatic LDL receptor
98
LDL receptor binds to ........ on the LDL
Apo B 100
99
PCSK 9 reduces LDL by what %
57% evolucumab
| 50-57 Alirocumab
100
Severe myopathy incidence with statins
0.1%
101
Increase in creatinine to say rhabdomyolysis
0.5 mg/dL
102
Statins with less penetration into muscle
Pravastatin, Rosuvastatin- water soluble statins
103
eGFR and cardiovascular risk
GFR<60- high risk of CAD
GFR < 30– very high risk
104
PCSK9 inhibitors approved for use in US and Europe
Evolocumab and Alirocumab
105
Lipoprotein small a is
LDL like particle PLUS apo lipoprotein small a which is attached to apo B of the LDL like particle
106
When to interrupt Statin therapy
CPK > 5 Times Normal, SGPT >3 Times Normal
Annals of Pediatric cardio 2014
107
What happens in liver with PCSK9 inhibitors
There will be more cholesterol UPTAKE by liver(as LDL-R in liver is unregulated)and liver will convert these to more bile acids.
108
INCLISIRAN is ————
| Its given as a ——————
PCSK9 synthesis inhibitor.(not Mab like alirocumab etc)
| It’s given as twice YEARLY injection
109
% of 0-14 yr population in world
26%
110
2017 ORION 1 Trial is with
INCLISIRAN- PCSK9 synthesis inhibitor
111
Study of CETP inhibitor Evacetrapib inCVD
2017 ACCELERATE study
112
INCLISIRAN lowers LDL by
50%
113
CETP inhibitor Evacetrapib reduces LDL by
Around 40% - 2017 ACCELERATE trial
114
Trials which showed LDL can be reduced to 20 without CNS or Liver problem
IMPROVE-IT( ezetemibe)
| FOURIER ( Evolocunab)
115
Ticagrelor needs to be stopped how many days prior to surgery
3 days( previously 5)
ESC 2017
116
Difference inDAPT duration between BMS&DES was removed in
ESC 2017
117
Short term DAPT means
| Ultra Short term means
Short:3-6 months
Ultra Short:1 month
New generation DES superior to BMS in both settings
ESC 2017
118
DAPT duration in bioreabsorbable scaffolds
At least 1 year
119
Role of PCSK9 in platelet function
Co activator
ESC 2017
120
PCSK9 function
Degrades LDL receptor
121
Study which showed lowering inflammation independent of cholesterol reduced Cardiovascular risk
2017 CANTOS trial with Canakinumab( IL-1 beta inhibitor)
122
........ of the heart attacks occur in people who do not have high cholesterol
Half
ESC 2017 leaflet
123
LDL levels as low as <8mg were achieved in ———trial
FOURIER
with PCSK9
124
Common cut offs for liver enz and CPK in statin trials
OT/PT- x 3 Times Normal
CPK- x5 Times Normal
125
Which study showed LDL as low as 8mg is safe with no safety concerns
FOURIER study with PCSK9
126
PURE study was done in
135,000 patients from 18 countries. Median fu of 7 yrs
Study showed high carb intake- worse total mortality
High fat intake associated with lower risk
127
Effect of saturated fat on cholesterol according to 2017 PURE study
LDL And HDL increases
But HDL increases more
So Total cholesterol/HDL ratio becomes better
128
2017 PURE study suggests use of ——— instead of LDL to assess effect of saturated cholesterol on cardiovascular risk
Apo B/Apo A1 ratio
129
In 2017 PURE study higher saturated fat intake was associated with———-in stroke risk
21% DECREASE in stroke risk🤯
130
Mortality risk reduction with
1. Saturated fat
2. Monounsaturated fat
3. PUFA
1. 14%
2. 19%
3. 20%
131
Recommended fat intake by 2017 PURE trialists
35%
Up from less than 30 in Guidelines
132
Which study showed LDL is not reliable in predicting effects on saturated fatty acids on future cardiovascular events
2017 PURE Trial
133
A study which showed reducing SBP below 120 is not useful
2016 HOPE study
Optimal BP in the trial appeared to be 130/80
134
Main procedural difference in 2017 SPYRAL HTN OFF trial was
Renal denervation was extended to the Branch vessel s
135
Very high or high risk groups who doesn’t need SCORE risk charts
ESC2017
Very High Risk
1. CKD
2. T2DM(as such)/ T1DM
3. Documented CVD including Carotid plaques
4. SCORE risk-10%
High risk
1. SCORE risk-5%
2. Markedly elevated single risk factor-Eg: Severe HTN, Familial dyslipidemia
136
SCORE risk estimates
10 yr risk of first FATAL atherosclerotic event(any CAD,PAD,ischemic stroke etc)
ESC 2017 claims most others estimate CAD risk only
137
How to convert fatal CVD risk to total(fatal +non fatal)
Men- x 3 times
Women- x 4 Times
Elderly- lower values.
ESC 2016 lipid Guidelines
138
Impact of DM on CVD risk
Men-x3 Times risk
Women-x 5 Times risk
According to SCORE risk( More risk than in Framingham cohorts)
ESC 2011
139
How to convert mmol of Cholesterol to mg
Mmol x 4 - 10:: my equation for ease
140
Stopping smoking reduces CVD risk by ....,,,
Half
| ESC 2017
141
Family history of premature CVD increases the risk of. CVD by
Males -x 2 Times
| Females- x1.7 Times
142
SCORE risk of 1% means———- risk
Moderate risk
Check - Abdominal obesity,Lp(a), Homocysteine, Fibrinogen, Apo B etc
143
Risk factor screening should start at——-age according to ESC 2017 lipid Guidelines
Males-40 yrs
Females-50 yrs
Family history, DM, Any e/o CVD in any vascular bed , HTN,Central Obesity Or BMI> 25 ,CKD-GFR<60,Autoimmune chronic inflammation (RA,SLE), Psoriasis, xanthomas, xanthelesma, premature arcus , antiretroviral therapy , premature CAD etc- early screening
Also Smoking
144
Definition of central obesity
Males- 90 cm waist
Females- 80 cm waist
European males-94
ESC 2017
145
Exponential increase in CVD when BMI is
27 or more
ESC 2017
146
Most common monogenic disorder associated with premature CAD
FH
147
Fried real dd formula not used if TG is
400 or more
148
Fasting is required only for which all lipid parameters
Only TG
Even Apo A1 , B etc no need of fasting
149
Lipid change happening in winter
Higher Total cholesterol and HDL cholesterol
150
Most risk estimates and almost all drug trials are based on
Total cholesterol and LDL cholesterol
151
Conditions with high cholesterol where risk scoring not required
Total cholesterol > 310, FH And FCH
Risk is always high
ESC 2017
152
Non HDL -C provide better risk estimates especially in
when high TG as in DM, CKD, MetS
Apo B also useful in this situation where small dense LDL would be high
153
False high TG levels are seen in
Hyperglycerolemia
154
Plasma Apo A1 levels which are considered to be equal to HDL levels
<120- males
| <140- females
155
The lipid which is genetically determined to a major extent
Lp(a)
156
Lp(a) is like LDL which contains
A Unique Protein called-
Apolipoprotein (a) .
This is structurally different from other Apolipoproteins
157
Apo E mutation causes
Familial dysbetalipoproteinemia- Apo E2 Homozygous
High TG, low HDL, high TC(FCH)
Xanthoma striatum palmaris, Tuberoeruptive xanthoma etc
158
Every 40 mg reduction in LDL reduces CVD risk by
22%
ESC 2011
159
SCORE project was done in
2003
160
NICE guidelines suggest evaluation for FH when
TC> 290
Use Simon Broome Criteria or DLCN Criteria
161
LDL targets in Very high risk and High risk subsets in ESC 2017
Very high risk-< 70 or 50% from baseline
| High- <100
162
Apo B treatment targets in Very high risk and High risk subsets
80 mg/dL And 100 respectively
Better than LDL alone in pts with HIGH TG
ESC2017
163
Specific target for hs crp May be useful is based on which all trials
2004 PROVE-IT TIMI 22
2004 to Z trial
2008 Jupiter trial
164
When to refer for DNA testing in FH
Simon Broome- Possible or Definite
DLCN- score 6
NICE guidelines
165
A diagnosis of Homozygous FH is considered when
```
LDL cholesterol ( not total cholesterol) > 500 in 16 years or older
> 425 in under 16
```
166
Every 10 kg loss LDL comes down by
8mg/dl In grossly obese
Effect is rather small
Even smaller is the reduction by regular exercise
ESC2017
167
The dietary factor with strongest impact on LDL
Dietary SFA
1.6 mg/dl for every 1% additional energy from saturated fat
168
SFA which will not increase TC
Stearic acid
169
Trans fatty acids in limited amounts is seen in natural foods like
Dairy products, Meat of ruminants
170
Effect of dietary cholesterol on CAD mortality
| 2. On cholesterol levels
1. Positive relation with CAD mortality partly independent of TC levels
2. Marked inter individual variability
171
Effect of dietary carbs on LDL
Neutral
172
PUFA effect on cholesterol
n3 series-no direct hypocholesterolemic effect
N6 PUFA- decreases LDL by 2 mg/dl for every 1% energy substitution of SFA with PUFA
173
Effect of habitual fish consumption on C.V. risk and lipids
Is associated with reduced C.V. risk that is mostly independent of any effect on lipids
174
A mono unsaturated fat effect other than on lipids
Significantly improves insulin sensitivity
So will reduce post prandial TG
175
In patients with high TG with chylomicrons the use of ——- avoid formation of chylomicrons
Medium chain TG
As these are directly transported to metabolized in liver
Long chain TG are transported as chylomicrons through lymphatic system while medium chain directly to the Portal system to Liver
176
Does dietary Fructose increase TG
Yes
ESC 2017
177
Effect of weight reduction on TG
20-30% reduction
178
Moderate consumption of Alcohol is
10-30g/day
1-2 drinks/day
179
Difference between SFA and Trans FA on Lipid
SFA- HDL and LDL increases
| Trans FA-HDL decreases and LDL increases
180
How phytosterols help in dyslipidemia
They compete with Cholesterol for intestinal absorption
181
Phytosterols can reduce TC&LDL by——-
upto 10%
182
Soy protein effect on LDL
Upto 5% reduction
183
Omega 3 can reduce TG by
30%
| May increase LDL by 5%
184
Low intake of fats and oil will reduce
Vitamin E and Essential fatty acids
185
N3 PUFA sources
Fish, Nuts, Soy, Flaxseed oil
186
Factors modifying SCORE risk
LVH,AFib, OSA, AI diseases, Central Obesity among others
187
Eliminating health risk behaviors can prevent .......%CVD and .......% cancers
80& 40
ESC 2011 lipid Guidelines
188
Poly pill approach is for people more than ....yrs
55
ESC 2016 lipid Guidelines
189
Markers of sub clinical vascular damage
1. ABI
2. Carotid USG
3. CAC- Coronary Artery calcification
ESC 2016 lipid Guidelines
190
Markers indicating higher cardiac risk in intermediate SCORE patients
```
hsCRP
Lp(a)
Apo B
Albuminuria
High TG
ABI 1.4
Carotid plaques
CAC>400
```
191
How to know pretreatment cardiac risk
Multiply by 3/2
Risk is usually reduced 1/3 by treatment
ESC 2016 lipid Guidelines
192
Stopping smoking in general will reduce......% of CVD risk
50%
193
Age for risk factor screening without any pre existing problem s
40- males
| 50- females or menopause
194
European statistics on male female ratio of CVD
Total CVD death: Male:Female-45:55
| In less than 65 age group -approx 70:30!ratio
195
Markedly elevated single risk factors which will include in high risk category to take statin
TC-> 310
BP>=180/110
Most people with DM
GFR-30-59
DM with end organ damage is in -Very high risk category
Severe CKD-GFR<30-Very high risk
Documented significant plaque
ESC 2016 lipid Guidelines
196
Premature at us cornealis means
<45 yr olds
197
An alternative to non HDL C is
Apo-B
ESC 2016 lipid Guidelines
198
Effect of DM on non fasting LDL levels
May show around 20 mg less
199
HDL C at increased risk of CVD is if less than
Males-40
| Females-50
200
Apo A1 levels corresponding to HDL levels of 40/50
<120/140
201
Lipoprotein (a) is
Routine LDL in which the ApoB protein of LDL is attached to another protein called Apolipoprotein small a. This small a has similarity to Plasminogen.
Hence this will compete with Fibrinogen and prevent thrombolysis
202
Drugs which can reduce Lipoprotein (a)
PCSK9 inhibitors And Nicotinic acid
| Reduce upto 30% . Clinical effect not known
203
The BP And DM targets to reduce risk of CVD according to 2016 lipid Guidelines
BP-<140/90
| DM-<7 HbA1c
204
In addition to the goals set for LDL the ESC lipid Guidelines also says
The LDL C should be reduced by at least 50%
205
Effect of dietary carbohydrates on HDL
Reducing Carbs can increase HDL
206
Mediterranean diet supplemented with extra virgin oil or Nuts reduced incidence of major CV events by
30%
ESC lipid Guidelines 2016 or 17
207
Relation between dietary cholesterol and CAD
Positive relationship exists between dietary cholesterol and CAD mortality which is
Partly independent of TC levels
208
Effect of carbohydrate on lipid profile
LDL-C- neutral
TG- increases
HDL-C - decreases
But fiber has a direct hypocholesterolemic effect
So use carb with fiber
209
For every 10 kg weight loss the LDL comes down by
8 mg
Regular exercise causes even smaller reductions in LDL
But exercise and weight loss goes beyond LDL reduction to reduce CV risk
210
SFA replaced by MUFA /n6PUFA/n3PUFA on HDL
MUFA-Neutral
N6- Slight decrease
N3- Almost neutral
211
Effect on HDL with 10 kg weight reduction
4 mg increase in HDL
212
Physical activity to increase HDL-C
5 km brisk walk / 5!days per week will roughly increases HDL by 5 mg
Roughly 1500-2000kcal / week
213
Calorie reduction for weight loss
300-500kcal/ day
214
Position of very low carbohydrate diet as per ESC LIPID GUIDELINES 2016
Not recommended
215
80% intake of trans fatty acids is from
Partial hydrogenated vegetable oils
216
Low intake of fats and oils causes
Low Vit E/Essential fatty acids/reduce HDL
217
Fatty acid intake as advised by ESC 2016
Predominantly from MUFA/N6PUFA(<10%_ to reduce lipid peroxidation and avoid decrease in HDL)/ N3PUFA
Cholesterol to< 300 mg esp in people with high cholesterol
ESC 2016
218
Moderate alcohol consumption according to ESC 2016 lipid Guidelines
Males- upto 20 gm( 2 drinks)
| Females-10 gms (1 drink)
219
2 GM of phytosterols daily can reduce LDL by
10%
HDL&TG- no effect
220
Which meta analysis showed that LDL reduction translates into lower CV events independent of mechanism involved
2009 Robinson Rt al JACC
221
Adverse effect if excess phytosterols
Decrease in carotenoids and fat soluble vitamin levels by the sterols
222
Bioactive ingradient in Red Yeast Rice
Monacolins
Similar to statins
223
Dietary fiber which reduces LDL-C
Water soluble fiber from oats
Barley beta glucan
At least 3 GM/ day
224
Omega 3 may reduce TG upto
30% ( Veg N3 are less effective)
At doses of 2-3 GM/ day
At higher doses may increase LDL
225
Study which supports Mediterranean diet forvCVD prevention
2013. PREDIMED trial
226
ESC LIPID GUIDELINES 2016 position on omega 3 for secondary prevention of CVD
No longer recommended
227
Recommended salt intake as per ESC 2016 LIPID GUIDELINES
< 5 gm salt
228
Tropical vegetable oils means
Palm oil and Coconut oil
229
For which group of patients according to ESC 2016 lipid Guidelines >50% LDL reduction is to be achieved
Very high risk and High risk
230
Effect of statins on TG and HDL
Reduce TG by 30-50%
HDL increases by 5-10%
231
Statins which are pro drugs
Lovastatin and Simvastatin
232
In rhabdomyolysis CK levels are elevated at least
10 Times
233
Frequency of muscle related complaints with statins 2013 circulation article
5%
10-15% in some observational studies
234
Mild ALT elevation occurs in ——% of patients On statins
0.5-2%
235
Clinically relevant SGPT elevation with statins
3 Times ULN On two occasions
236
mild ALT elevations due to steatosis- statins will...
No indication that statins cause worsening of Liver disease
ESC 2016 lipid Guidelines
237
The number needed to cause one case of DM with statin use
255 pts over 4 years
ESC 2016 lipid Guidelines
Relative risk increases 9%
Absolute risk 0.2%
238
Proteinuria and Statins
Increased frequency with all Statins
12% with 80 mg Rosuvastatin
At 40 mg it is similar to other statins
ESC 2016 lipid Guidelines
239
The apparent reason for proteinuria with statins
Due to reduced tubular reabsorption and not due to glomerular dysfunction
240
Statins not undergoing Hepatic metabolism via CYP
Pravastatin, Rosuvastatin, Pitavastatin
241
CCBs which may increase statin toxicity
Amlodipine/Verapamil/ Diltiazem
By CYP3A4 interaction
ESC 2016 lipid Guidelines
Ranolazine And Amiodarone also
242
Most of the bile acids are reabsorbed and returned to liver by
Active absorption at terminal ileum
243
Bile acid sequestrants- the 2 older ones and the new one
Cholestyramine, Colestipol- resins
New- Colesevelam- a synthetic drug
244
Action on blood sugar by Colesevelam
Reduces blood sugar
245
Effect of bile acid sequestrants on LDL,HDL,TG
LDL-20% decrease
HDL-neutral
TG- may increase in some predisposed pts
246
Precautions with bile acid sequestrants
Take 4 hr before or 1 hour after other drugs With PLENTY of Water
Fat soluble Vitamin deficiency can happen
247
The drug which reduces intestinal absorption of dietary and biliary cholesterol without affecting absorption of fat soluble nutrients
EZETEMIBE
By acting on NMC1L1- Neimann-Pick C1Like Protein
248
EZETEMIBE reduces LDL by
20%
249
EZETEMIBE studied after ACS
2015 IMPROVE IT
250
Two studies which showed EZETEMIBE was effective in reducing CV events
2008 SEAS trial- Aortic Stenosis
2011 SHARP trial- CKD
251
Most frequent adverse effect of EZETEMIBE
Muscle pain & Moderate elevation in liver enzymes
252
PCSK9 reduces LDL by
60%
No effect on HDL and TG
253
The subset which doesn’t respond to PCSK9 inhibitors
LDL -R deficient Ho FH
254
PCSK9 adverse effects
Flu like symptoms
Itching at injection site
Pt reported neuro cognitive effects- needs more scrutiny
255
Nicotine can acid effect on LDL,HDL,TG
LDL-15%
HDL-25% increase
TG-30%
At 2gm/day
256
ESC 2016 lipid Guidelines recommendation level for PCSK9 in statin intolerant pts
2b
257
Remnant cholesterol is calculated as
TC- HDL+LDL
258
Percentage of people with TH> 150
1/3 rd If adults
259
Effect of pregnancy on TG
Double during 3rd trimester
260
Moderate TG definition as in ESC 2016 lipid Guidelines
Adapted from EAS
150- 880. (10 mmol/l)
261
Recommendation for drug treatment in HTG- ESC 2016 lipid Guidelines
> 200
High risk for CVD
Class 2a- drug treatment to be considered
DOC- Statin Class 2 b
If >200 despite statin add fibrate- 2b
262
Dosage of PCSK9 is every
TWO weeks
Ie Monthly 2 injections
263
Relationship between carbohydrate intake and MI occurrence as per 2017 PURE study
No relation
Also no relation to Stroke
264
Relation between fat intake and MI as per PURE 2017 study
1. No relation with MI
2. Sat fat reduced stroke
3. Total mortality reduced with increased fat intake
But increased carb intake increased mortality
The difference in mortality in both groups were due to changes in non CVD mortality
265
PURE Study 2017 was done with > .......number of cases from ..... countries
```
135,000
18 countries
35-70 yrs population
2003-2013 recruitment
Median fu- 7.5 years
```
6000- total mortality
5000–CVD events
266
Countries like Finland have a very high intake of saturated fats in the range of
20% of total energy
From PURE 2017 study discussions
Guidelines as of 2017 recommend <10% of saturated fat intake
267
Argument against using only LDL as the marker in assessing effect of Saturated fat intake
1. Cholesterol/HDL ratio may be changed favorably
2. Effect on Apolipoproteins is not known
3. May have effects on BP
The 3 arguments presented in PURE 2017 discussion
268
The only 3 high income countries in PURE 2017 study
UAE
Canada
Sweden
269
What % of the PURE 2017 cohort had CVD and were excluded from study
5%
Around 7000 had CVD
270
Percentage of Carb/Fat/Protein intake in South Asia in PURE 2017
Study
65/20/10 roughly
271
Relation between total mortality and PUFA/MUFA/Sat FA
Reduced with more intake of PUFA and MUFA and Sat fats
PURE 2017 study
272
Highest quintile of fat and sat fat intake in PURE 2017 study
33-38% for total fat
12-15% for sat fats
Both of total energy
273
Total mortality increased with carb when intake was more than.... in PURE2017 study
65% ie 4th and 5th quintiles
274
As per PURE 2017 study sat Fat intake of ..... reduced stroke
12-15% roughly
275
Effect of high Carbohydrate intake on Dyslipidemia
From PURE 2017 Discussion
1. High TG and low HDL
2. Apo B/Apo A ratio increased
3.Increased small dense LDL
And also increases BP
276
The relation between low Carb intake and mortality in PURE study of 2017
<50% energy quartile didn’t show any risk reduction
So not advisable as such
So the authors suggest moderate intake in range of 50-55%
Total fat they suggest- about 35%
277
First large study to show the effect of low level Sat fat intake and mortality and CVD events
PURE 2017
Doesn’t reduce total mortality or stroke and this quintile when compared to 15% had higher events
So less than 7% may be harmful as per PURE discussion
278
Strongest risk predictor of MI and stroke as per PURE 2017 discussion
ApoB/ApoA1 ratio
279
The 2017 study which showed that there is no detrimental effect of fat intake in CVD events
PURE study
280
The effect of increasing carb intake and fat intake on cardiovascular mortality or on major CVD as per 2017 PURE study
No effect
The effect was on total mortality and non cardiovascular mortality
281
Mortality benefit was maximum when carbohydrates were replaced with... ......in PURE 2017 study
PUFA
Still no effect on CVD.
Effects minimal when replaced with sat fat, MUFA or proteins
282
The simplistic thinking that is questioned by PURE 2017
Can the effect of diet be captured by a single bio marker eg. like LDL or BP alone..It’s much much more complex. Multiple bio markers should be always considered in assessing effect of diet.
Similar Pr. Yusuf
283
Arguments against PURE 2017
Some thoughts
Comparing lowest BMI to highest BMI is not the right thing to do. Here they have compared the quintile 1 to 5.
The sweet spot may be somewhere in between
It may be a U shaped relation
Also didn’t swap PUFA for sat fat. Did only for carb.
Used a single questionnaire to assess food intake over 7 years in addition to possible recall bias
Also only one blood sample at the start of the study
Also risk ratios of less than 2 may be questionable
It’s only an observational study
It’s good to have aHealthy dose of HUMILITY in dietary advices
284
Argument against AHA 2017 guidelines on sat fat intake based on PURE study
AHA suggests less than 6% sat fat intake. But in PURE study it was linked to higher mortality ( only the 4th and 5th quintiles were good
285
Effect of saturated fat on BP in PURE 2017 substudy
Increases. Also carbs
Protein a/w decrease in BP
286
Mean saturated fat intake in North America and Europe
11%
China around 6%
287
SCORE risk grading
Low-<1%
Moderate-1-5%
High<10%
V.high-10%
288
Alirozumab and Evolocumab was approved by US FDA in
2015
