SR cardiology in LPS institute of cardiology kanpur

1. Dr. Dibbendhu Khanra

2. Single
problem
Single
strategy
Statins
Single
calculation
DON’T CHASE TARGETS
2013
ACC/ AHA

3. Paradigm
Shift
New cholesterol treatment guidelines could double number of
Americans taking statins
About 70 million Americans could take statins under new guidelines

4.  32 year male IT professional
 Occasionally drinks/ smokes
 Non DM/ non HTN
 85 kgs/ Cant go to gym
 Father died of heart attack at 50 years of age
 Recently married
 Very anxious of heart disease
 CAG normal
 LDL 100
 TG 350
 HDL 30
 ACC risk calculator: 2%
 Would you give statin or not?
 If given how long?
 What about the side effects?

5. 8 meetings
153 experts
18 states
30 cities

6. INDIAN
CVD
BURDEN?

7.  more than 60 million
people with coronary
heart diseases by 2015
The health & family welfare
ministry Projection

8. 0
1
2
3
4
5
1990 2000 2010 2020
2.26
3.01
3.8
4.77
CVMortality(Millions)
Heart. 2008 Jan;94(1):16-26.

9. http://www.cadiresearch.org/topic/asian-indian-heart-
disease/cadi-india/premature-heart-disease

10. 10
Urbanization
DM,HT,DYSLIP
>
Improved Life
Expectancy
Changing
dietary
pattern
Reduced
physical
activity
Stress
• Increase in
the number of
CVD cases
World Development Indicators, World Bank.
India’s Pace of Urbanization Speeds Up, Wall Street Journal, July 2011
Food and Nutrition in India: Facts and interpretation.Dreze J, et al. Economic & Political Weekly, February 2009.
Smoking & Heart Disease. Cleveland Clinic.
Joshi SR, et. al. India -Diabetes Capital of the World : Now Heading Towards Hypertension. Journal of Association of Physicians in India. 2007; 55:323-324
Xavier D, et.al. Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data. The Lancet.2008;371(9622): 1435-1442.
World Health Survey, World Health Organization.
• Earlier onset
of disease

11. CAD
in
Indians

12. However
westernized we get,
INDIANS are still
INDIANS,
you know?
Oh, I see

13. High smoking
High BP
But
Heart diseases among
Chinese , very low
& Japanese , the lowest

14. TRADITIONAL
CV RISKS
IN
INDIA?

15.  66 Million Cases
 35 Million Undiagnosed
 8.6% Prevalence
 Over 1 Million Deaths
IDF, Diabetes Atlas, 6th edition revision, 2014

16. INTERHEART Study
Dyslipidemia is the most common risk factor

17. Relative risk
reduction
2 yr event
rate
Huang et al. Am J Med 2001;111:633-642
Turner R.C. BMJ 1998;316:823-828
He et al. JAMA 1999;282:2027-2034
Antitrombotic Trialits BMJ 2002;324:71-86

18. Men Women
Total cholesterol

19. INDIAN DYSLIPIDEMIA

20. Jaipur
heart
watch
study

21. ATHEROGENIC DYSLIPIDEMIA
Low HDL (Most common)
High TG
High Lp(a)
High LDL is very uncommon
Apo B: Apo A1 is the best biomrker

22. Lipid screening at 20 years of age

23. More severe
form with
poor
outcome
Disease at
early age
Low
prevalence of
traditional
risk factor
High
disease
burden

24.  Not validated in
Indians
 10 year risk only
 Only conventional
risk factors
 Needs computer

26. NON
TRADITIONAL
CV RISKS
IN
INDIA?

27.  Both LDL-C and HDL-C were found to be
independent predictors of CAC
 CAC score >400 had 100% specificity

28.  For 0.1 mm increase in CIMT the future risk of MI increased by 10-15%
 A 10% reduction in LDL-C per year accounted for a reduction of CIMT by 0.73
 presence of carotid plaques is a marker of already existing ASCVD

30.  more common among
CAD patients with
existing family history
 Lp(a) levels in Asian
Indian newborns were
significantly higher than
in Chinese in Singapore
 Level > 20 mg/dL
indicates increased
ASCVD risk in Indians

31.  presence of obesity
and/or metabolic
syndrome in an
individual who is
otherwise at low 10-
year risk of ASCVD
should indicate high
lifetime ASCVD risk.

32.  A 5-μmol/L tHcy increment elevates CAD risk by as
much as cholesterol increases of 0.5 mmol/L (20
mg/dL)
 Very high prevalence of hyperhomocystinemia (>15
µmol/L) in 75% of subjects in India, which was
strongly correlated with cobalamin deficiency
 impaired cobalamin status appears more important
than folate deficiency among Asian Indians

33.  significant ASCVD risk
reduction with statin in
individuals with elevated CRP
despite relatively normal LDL-C
 A value of > 2 mg/l of hs-CRP
indicates increased ASCVD risk.
 When the value is >10 mg/L, it
usually indicates a non-
atherosclerotic cause of
Inflammation
 But Quality control and proper
standardization of hs-CRP is
challenging in India

34. Risk factors
NO LDL NO CRP
NO HOMOCYSTEINE
CAC
Aortic stiffness
CIMT
Lp(a)
MertS

35. Estimate lifetime risk
Validated in indians
Non-conventional risk factors
<30% = LOW RISK
30-44% = MODERATE RISK
>45% = HIGH RISK

36. Identify
High Risk
patients
Assess
Risk factors
Estimate
Lifetime risk
The Indian Approach

37. 1. History of MI or documented CAD
2. History of ischemic stroke or TIA
3. hemodynamically significant carotid plaque
4. Atherosclerotic peripheral arterial disease(ABPI<0.9)
5. Atherosclerotic aortic aneurysms
6. Atherosclerotic renal artery stenosis
Pre-existing ASCVD

38. 30-44%
risk
>45%
risk
Moderate
risk
High
risk
Indian
risk
stratification

39. SETTING
THE
INDIAN
TARGETS

40. Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):269-279

41. High dose
(ROSUVA)statin
regresses
atherosclerosis
• LDL should be the primary target
• the lower LDL the better
• LDL<50 mg/dl is safe

42. 4HPS Collaborative Group. Lancet. 2002;360:7-22.
5Shepherd J et al. N Engl J Med. 1995;333:1301-1307.
6 Downs JR et al. JAMA. 1998;279:1615-1622.
14S Group. Lancet. 1994;344:1383-1389.
2LIPID Study Group. N Engl J Med. 1998;339:1349-1357.
3Sacks FM et al. N Engl J Med. 1996;335:1001-1009.
LDL
N 4444 4159 20 536 6595 66059014
-35% -28% -29% -26% -25%-25%
Secondary High Risk Primary
PatientsExperiencing
MajorCHDEvents,%
Placebo
Statin
19.4
12.3
10.2
8.7
5.5 6.8
28.0
15.9
13.2
11.8
7.9
10.9
Many CHD Events Still Occur in Statin
Treated Patients
25-40% CVD Reduction Leaves High Residual Risk
P = 0.003
P <0.001
P = 0.003
P = 0.0001
P <0.001
P <0.001

43. Residual CVD Risk with Intensive Statin
Therapy Less, but Still Unacceptably High
PatientsExperiencing
MajorCVDEvents,%
PROVE IT-TIMI 222 IDEAL3
TNT4
n
LDL-C* mg/dL
1Superko HR. Br J Cardiol. 2006;13:131-136.
2Cannon CP et al. N Engl J Med. 2004;350:1495-1504.
3Pedersen TR et al. JAMA. 2005;294:2437-2445.
4LaRosa JC et al. N Engl J Med. 2005;352:1425-1435.
4162 8888 10,001
95
*Mean or median LDL-C after
treatment
62 104 81 101 77
Statistically significant, but clinically inadequate CVD reduction1
Standard statin therapy
Intensive high-dose statin therapy

44. Event Rate
(No Diabetes)
Event Rate
(Diabetes)
On Statin On Placebo On Statin On Placebo
HPS1* (CHD
patients)
19.8% 25.7% 33.4% 37.8%
CARE2† 19.4% 24.6% 28.7% 36.8%
LIPID3‡ 11.7% 15.2% 19.2% 22.8%
PROSPER4§ 13.1% 16.0% 23.1% 18.4%
ASCOT-LLA5‡ 4.9% 8.7% 9.6% 11.4%
TNT6║ 7.8% 9.7% 13.8% 17.9%
*CHD death, nonfatal MI, stroke, revascularizations
†CHD death, nonfatal MI, CABG, PTCA
‡CHD death and nonfatal MI
§CHD death, nonfatal MI, stroke
║CHD death, nonfatal MI, resuscitated cardiac arrest, stroke
(80 mg versus 10mg atorvastatin)
1HPS Collaborative Group. Lancet. 2003;361:2005-2016.
2Sacks FM, et al. N Engl J Med. 1996;335:1001-1009.
3LIPID Study Group. N Engl J Med. 1998;339:1349-1357.
4Shepherd J, et al. Lancet. 2002;360:1623-1630.
5Sever PS, et al. Lancet. 2003;361:1149-1158.
6Shepherd J, et al. Diabetes Care. 2006;29:1220-1226.

45.  there are several atherogenic
lipoproteins and LDL accounts
for only about 75% of them
 residual risk of ASCVD in
statin-treated patients
remains as high as 55%-70%.
 It is thus evident that in order
to reduce ASCVD effectively,
we need to concentrate on all
atherogenic lipoproteins, and
not just LDL alone
Non HDL
cholesterol
TG
Small
dense LDL

46. non-HDL-C has been shown to
correlate well with subclinical
atherosclerosis

47. Non-HDL-C is particularly
informative in diabetics who
tend to have higher TG levels

48. predictive accuracy of
non-HDL-C in patients with
relatively low TG (<200mg/dL)

49. LDL-C lost its predictive value
when TG levels exceeded 400mg/dL
Non-HDL-C seems to
predict ASCVD risk equally
well regardless of TG levels

50. increased non-HDL-C is associated
with increased risk of future CV events
even if LDL-C is under
control with statin

51.  Better correlate of ASCVD than LDL
 Includes TG and Lp(a)
 Does not need fasting
 Can be easily calculated by total cholesterol and HDL
 Surrogate for small dense LDL

53.  strong linear association between
TG levels and CHD risk
Do not underestimate high TG

54. Small
dense LDL Large LDL
Atherogenic
TG>250
Phenotype B
TG <100
Phenotype A
At a fasting TG concentration <100 mg/dL,
85% of the population has pattern A (less atherogenic)
At a fasting TG concentration >250 mg/dL,
85% will have pattern B (highly atherogenic)

55.  Clinically unimportant
increase in TG concentrations,
by 0·2–0·4 mmol/L (18-36
mg/dL) on average, two to six
hours after eating normal
meals.
 even a non-fasting
concentration predicts
increased CV risk
Indian patients are
unpredictable

56.  631,762 individuals
 with no prior cardiac
conditions,
 with a mean follow up of
4.9 years,
• very high levels of HDL-
C were associated with an
increased risk of death
from both CV and non-
CV causes, compared
with intermediate HDL-
C levels.

57.  Prevalence of low HDL-C levels was much higher in
the South Asian populations than in the other
populations (82% vs 60% of acute MI cases)
 increaseing HDL-C was associated with a mere 13%
reduction in MI risk in South Asians as compared to
23% risk reduction in the other Asians
 The patients with low HDL-C are three times more
likely to die after an acute coronary event

58. THERAPY FOR
INDIAN
DYSLIPIDAEMIA

60. Smoking
 It is never too late to quit
smoking. After quitting
smoking,
 the ASCVD risk decreases
by 50% within 2 years.
 Alcohol consumption
was not found to be
protective among South
Asians
Alcohol

62. Vegetarians are not protected

63. Eat baked or
boiled fish at
least twice per week

64. As per the ICMR in 2014,
392 million people were inactive in India
which represented nearly
1/3rd of our population.

65. Mr. Modi, is it true
that there are 4
billion lazy people
in India?
Yes, that’s why I
invented
WORLD YOGA DAY

66. Yoga may help in improving
lipid profile in patients
suffering from ESRD
Bairey Merz CN, Dwyer J, Nordstrom CK, Walton KG,
Salerno JW, Schneider RH. Psychosocial stress and
cardiovascular disease: Pathophysiological links.
Behav Med 2002; 27:141-147

68.  Treatment of 1000 patients with a statin for five years would
prevent 18 major ASCVD event (Cochrane)
 Reduction of 1 mmol per liter (39 mg/dl) in LDL-C levels
yielded 21% risk reduction irrespective of LDL baseline
(CTT)
 In individuals with 5-year risk of major vascular events
<10%, each 1 mmol/L reduction in LDL-C produced an
absolute reduction in major vascular events of about 11 per
1000 over 5 years (CTT)
 Those who achieved LDL-C <50 mg/dL had 65%
reduction in the risk of major CV events (JUPITER)
 23% of the subjects reached LDL-C level of <40 mg/dL
with no adverse effects (JUPITER)

70.  underuse of low-cost medicines for secondary
prevention among participants with a history of CVD
70
The PURE Study: a prospective epidemiological survey. Lancet 2011;378:1231–43.

71.  45-64 year old men (n= 6595) with high LDL
cholesterol were randomized to receive pravastatin
40mg once daily or placebo for an average of 4.9 years.
And followed up for 20 years (without statin)
 Men allocated to pravastatin had
- reduced all-cause mortality
- 21% decrease in cardiovascular death
- 18% for any coronary event (p=0.002),
- 24% for myocardial infarction (p=0.01) and
- 35% for heart failure (p=0.002)
Statin: Legacy Effect

73. Atorva=Rosuva

74. Rosuvastatin for primary prevention

75. SATURN

76. Statin doses Statin Vices

77. Statin
& DM
 treatment of 255 people with
statins for 4 years would
result in to 1 additional case
of diabetes mellitus
 risk of new onset diabetes
with intensive statin therapy
is approximately 3 per 1000
patient-years and with
moderate intensity statin
therapy 1 per 1000 patient-
years
 Its true frequency is
unknown; however,
reported incidence is
around 10%. Routine
monitoring is not
needed
Statin
& muscle symptoms

78.  A meta-analysis of 18
trials providing data for
45058 participants,
including 2870 major CV
events, 4552 coronary
events, and 3880 deaths
 It was found that fibrates
could reduce the risk of
major CV events
predominantly by
prevention of coronary
events
 patients with higher
baseline TG and lower
HDL-C levels benefited
from fenofibrate therapy
in addition to pre-
existing simvastatin
(ACCORD)

79. Look for reversible causes
Eg.DM, hypothyroidsm, CKD,
immuocomprised
LSM
TG<500 TG>500
Statin
Achieve LDL target
Achieve non HDL cholesterol
Non-statin drugs
Fibrate
Achieve TG target
Statin
Achieve LDL and
non HDL cholesterol target
Hyper
TG

80. Drugs Trials Outcome Comment
Rosuvastatain ASTEROID,
ARBITER,
METEOR
Positive Also regression of
atherosclerosis
NIACIN HATS
ARBITER 2
ARBITER 3
Positive In combination to
statin
HPS2THRIVE
AIMHIGH
Negative In combination to
statin
FIBRATE FIELD Positive 27% redction in
cardiac events
ACCORD Positive In combination to
statin
CETP Inh Torcetrapib
Dalcetrapib
Negative Harmful
Anacerapib
Evacetrapib
Ongoing

81. Curing atheroclerosis

82. THE
INDIAN
LIPID POLICY

84.  Screen all adults at 20 years of age/college entry
 “magnificent seven”
1. No tobacco
2. Physical activity: ≥150 min moderate intensity or equivalent
exercise per week
3. Body-mass index <23 kg/m2
4. Healthy diet: achieving at least four of the five important
dietary components, focusing on fruits and vegetables, fish,
fibre, and sodium intake and sweetened beverage intake
5. LDL-C level should be below 100mg/dl
6. Blood pressure: <120/80 mmHg
7. Fasting plasma glucose level: <100 mg/d

85. Recommendations made in the consensus statement
are not a mandate to the medical community
8 meetings
153 experts
18 states
30 cities

86. Multiple
problem
Multiple
strategy
Statins
Non-statins
Yoga
Multiple
calculation
Set Target
According To Risk
2016
Indian
guideline
Risk counting
Non-traditional risk factors
JBS3 – lifetime
Non-fasting
Non-HDL cholesterol

88.  32 year male IT professional
 Occasionally drinks/ smokes
 Non DM/ non HTN
 85 kgs/ Cant go to gym
 Father died of heart attack at 62 years of age
 Recently married
 Very anxious of heart disease
 CAG normal
 LDL 100
 TG 350
 HDL 30
Major RF
Moderate
RF
Moderate
Risk
Major RF
Lp (a)40
CIMT normal
CAC 250A
High Risk
Statin
At least 5 years

89. Questions answered
 TG
 Non HDL chol
 Lifetime CV risk
 Non-traditional risks
 noninvasive imaging
 20 vs 40
 Atorva vs rosuva
 HF, hemodialysis
Questions unanswered

90.  complex
 lots of investigation
 till not validated
 not evidence based
 statinization
MADE IN INDIA

91. Thank You