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Coronary Artery disease in an epidemic
proportion in India:
Risk Factors and their management

Dr Javed Akhtar

Consultant...
NOT ANGINA

ANGINA

ANGINA-Chest pain distribution
SOME FACTS ABOUT HEART DISEASE









82,000 die every year in UK due to CAD
It is the leading cause of death for b...
Atherosclerosis: When does it begin?
100
Prevalence of coronary
atherosclerosis (%)

85%
80

71%
60%

60
37%

40
20
0

17%...
Atherosclerosis Timeline
Foam
Cells

Complicated
Fatty Intermediate
Fibrous
Lesion/
Streak
Lesion Atheroma Plaque
Rupture
...
Atherosclerosis is a Chronic Inflammatory Disorder
American Heart Association
10 Factors That Increase the Risk of Heart Disease and
Heart Attack:
1) Diabetes Mellitus
2) ...
Hypertension




Substantial Under-diagnosis
Under-Treatment
Poor Rates of BP control
High Blood Pressure strain on the heart
High Blood Pressure
Hypertension
A Risk Factor for Cardiovascular Disease
Coronary
disease
50
Biennial
ageadjusted
rate per
1000
subjects

Per...
Increasing BP is closely associated with
increasing risk of death from stroke
Relative risk of stroke mortality
30
DBP
25
...
Increasing BP is closely associated with increasing risk of
death from coronary heart disease
Relative risk of CHD mortali...
Increasing BP is closely associated with
increasing risk of end stage renal disease
Adjusted relative risk
25

*

22.1

20...
Impact of High-Normal BP on CV Risk
16

Cumulative
incidence of
CV events
(%)

High-normal BP

Men

14
12
10

Normal BP

8...
Implications of Small Reductions in DBP
for Primary Prevention
DBP reduction
0

7.5 mm Hg

5-6 mm Hg

-6

-10
-20

Risk
re...
Benefits of Tight BP and Tight Glucose Control
UKPDS
0

Stroke

Any diabetes- Microvascular Diabetes-related
endpoints
rel...
Risk associated with LVH secondary to
Hypertension

LVH is a major risk factor for CVD
1-6 fold higher risk for angina
2...
Management of Hypertension

Drugs
1. ACE-inhibitor/ARBs
2. Calcium Channel Blocker: Amlodipine/Felodipine
3. Diuretic: B...
Why do so many patients fail to achieve
BP goal?










Poor compliance
Ineffective drugs
Occasional missed do...
Multiple antihypertensive agents are needed to
reach BP goal
Trial (SBP achieved)
ASCOT-BPLA (136.9 mmHg)
ALLHAT (138 mmHg...
Hypertension


The single most important aspect of treating a
patient with Hypertension is to achieve
Optimal Blood Press...
Hypertension
Life Style Advice
Reduce Body weight (Maintain BMI 20-25
Kg/m2)
 Reduce dietary Sodium Intake to
<100 mmol/d...
Wrong Dietary Habits
Certain Facts about South Asians



Diet high in fat and low in fruits & vegetables
Certain Facts about South Asians



Simply a cultural difference?

200g Margarine

2 Kilos Ghee!
Stress related Heart disease
Lack of Exercise
Genes and environment in type 2
diabetes and atherosclerosis
Waist circumference as a measure of
body fat distribution

Women
>80 cm = Increased risk

cm

Men
>88 cm = Increased risk
...
Waist Circumference

A VITAL SIGN!!!
SMOKING
Certain Facts about South Asians



Smoke more than others
Harmful Chemicals in Cigarettes:









>4,000 chemicals inside a cigarette
The two most harmful chemicals are:
Nic...
Smoking

People who smoke:






High risk for IHD
High Blood pressure
Heart attacks
COPD/Chronic bronchitis
Lung Can...
Smoking: Some facts







10 Million People smoke in England
120,000 deaths in UK are Smoking related
50% of Smokers...
Smoking: Some facts


Smoking 3-6 Cigs/day doubles the
chance of having Heart attack



Smokers are > twice likely to ha...
Non-Smoker’s Lungs
Smoker’s Lungs
Hyperlipidaemia
Do Statins do more than lower lipids?
Apart from lowering Total Cholesterol, LDL and Triglycerides,
and
slight increase in...
% reduction LDL cholesterol

Correlation between percent reduction of LDL
cholesterol and percent reduction of
CAD mortali...
% reduction CAD morbidity

Correlation between absolute reduction of LDL
cholesterol and percent reduction of CAD morbidit...
Low HDL-C Levels Increase CHD Risk Even When
Total-C Is Normal (Framingham)

.91
11
.24
11

5
9.0

.7
10
6.6

3
5.5

6
6.5...
MIRACL: Addressed a Research Gap
Acute coronary
event
No history of CAD

Unstable CAD

Stable CAD

4 mo
AFCAPS / TexCAPS/
...
ASCOT-LLA


The prevention of coronary and stroke events with Atorvastatin in:
Hypertensive patient with at least 3 CV ri...
Study design
CCB = Calcium channel blocker
ACEI = ACE inhibitor
TC = Total cholesterol

R

9,000
9,000
β-blocker ± diureti...
Primary endpoint: Cumulative incidence of
non-fatal MI & fatal CHD
Atorvastatin 10 mg

Proportion of patients %

100

Plac...
Cumulative incidence for fatal &
non-fatal stroke
Atorvastatin 10 mg

Proportion of patients (%)

Number of events

89

Pl...
Effect of atorvastatin & placebo on study
endpoints
Primary Endpoints
Non-fatal MI (incl silent) + fatal CHD
Secondary End...
Summary
Primary endpoint :
Treatment with atorvastatin 10 mg/day (vs placebo) in hypertensive patients with multiple
risk ...
Conclusion
In hypertensive patients with multiple risk factors
at modest risk of CHD, with average or lower than
average c...
Diabetes:
Is it coronary equivalent?
Global projections for the diabetes
epidemic 1995-2010
Diabetes

Risk factors for developing Diabetes:
 Obesity
 Lack of Exercise
 sedentary life style
 Waist girth increase...
So WHO is at risk ?

Diabetes - a Major CHD Risk Factor

40

7 year follow-up

Incidence of MI after

50

30
20
10
0

Norm...
Survival Post-MI in Diabetic and Non-diabetic Men
and Women: Minnesota Heart Survey
100

MEN

100
n=1628

80
60

Diabetes
...
Diabetes and CVD

In people with diabetes:
1. Heart disease twice as often as people without diabetes.
2. CVS complication...
Insulin Resistance
The RIGHT drug for the RIGHT patient
This profile could be

BADNEWS
for patients with the Metabolic Syndrome and/or
type 2...
Insulin resistance is linked to a range of CVD
risk factors
Insulin resistance

Endothelial
dysfunction

Hypertension

Dys...
Proportion of patients with cardiovascular disease increases with duration of type 2 diabetes

48%

29%
21%

24%

15%

<=2...
Investigations in suspected
coronary artery disease
Investigating suspected coronary artery disease
Blood tests: FBC, U&E, FBS, Fasting lipids, GTT
CXR
ECG
Echocardiography
N...
Echocardiography
Normal chocardiography
Antero-septal MI
Antero-septal MI
Anterior MI
Anterior MI
Treadmill Test (Exercise ECG teat)
Stress Thallium Test
Severe coronary artery disease
Lt Main coronary stenosis

LMCA stenosis RAO caudal.avi.mp4
Initial Treatment


A = Aspirin and Antianginal therapy



B = Beta-blocker and Blood pressure



C = Cigarette smoking...
Revascularization for Chronic Stable Angina
coronary artery bypass surgery - Class I


significant left main disease (>60...
Revascularization for Chronic Stable Angina
 in patients with prior PCI, CABG or
PCI or CABG - Class I
PCI with a large a...
Severe coronary artery disease
PCI to LAD
Severe LAD stenosis before D1
PCI and ACS

50 yr old man, ST dep anterior leads, trop +ve

Case 1
Coronary Artery Bypass Graft
Coronary Artery Bypass Graft
Exercise

Daily exercise for 30 Mins
Exercise
Take-Home Message
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
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
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








Be aware of health issues
Body weight
Regular exercise
Dietary habits: More v...
Thanks
Dr Javed Akhtar
Coronary Artery Disease in Epidemic Proportions in the Indian Subcontinent
Coronary Artery Disease in Epidemic Proportions in the Indian Subcontinent
Coronary Artery Disease in Epidemic Proportions in the Indian Subcontinent
Coronary Artery Disease in Epidemic Proportions in the Indian Subcontinent
Coronary Artery Disease in Epidemic Proportions in the Indian Subcontinent
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Coronary Artery Disease in Epidemic Proportions in the Indian Subcontinent

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Coronary Artery Disease in Epidemic Proportions in the Indian Subcontinent by Dr Javed Akhtar

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  • There is now a substantial body of research that suggests that the origins of atherosclerosis begin at an early age.
    This slide shows data from 262 heart transplant donors.1 Sites with an intimal thickness of ≥0.5 mm were defined as atherosclerotic. Results showed that the extent of atherosclerosis increases progressively with advancing age. Among the 13- to 19-year age group, atherosclerotic disease was present in 17% of subjects. By age 40, &gt;70% of individuals had ≥1 atherosclerotic lesion.
    These data suggest that coronary heart disease (CHD) is highly prevalent and that even relatively young individuals may have a substantial plaque burden that will require aggressive intervention.
    Tuzcu EM, Kapadia SR, Tutar E, et al. High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound. Circulation. 2001;103:2705-2710.
  • Atherosclerosis is a progressive disease involving the development of arterial wall lesions. As they grow, these lesions may narrow or occlude the arterial lumen. Complex lesions may also become unstable and rupture, leading to acute coronary events, such as unstable angina, myocardial infarction, and stroke.
    Pepine CJ. The effects of angiotensin-converting enzyme inhibition on endothelial dysfunction: potential role in myocardial ischemia. Am J Cardiol. 1998; 82(suppl 10A):244-275.
  • Slide 2
    Prospective analysis of the 36-year follow-up data from the Framingham Heart Study demonstrates that hypertension (blood pressure &gt;140/90 mm Hg) predisposes powerfully to all major atherosclerotic cardiovascular (CV) disease outcomes, including coronary heart disease, stroke, peripheral artery disease, and cardiac failure.
    Because of the high prevalence of hypertension in the general population and its sizable risk ratio, approximately 35% of atherosclerotic CV events may be attributable to hypertension [Kannel, 1996].Hypertension imparts a 2- to 4-fold increase in the risk for major CV events. This increased risk occurs among both men and women. Hypertension clusters 80% of the time with one or more additional risk factors that are metabolically linked with coronary artery disease, such as dyslipidaemia, insulin resistance, glucose intolerance, and obesity.
  • In a study of &gt;340,000 men without previous myocardial infarction (MI), elevation of both systolic and diastolic blood pressure (DBP and SBP) were associated with an increased risk of stroke mortality.
    The increase in relative risk was particularly marked with rising SBP; in patients with a SBP of 180–209, the relative risk rate was 10.7, while in those with a SBP of ≥210, the risk rate is 24.3.
    With DBP, the increase in risk was not as numerically large as that observed for SBP. The relative risk more than doubled for patients with DBP of 90–99, and in patients with a DBP ≥120 the relative risk was 12.57.
    Abbreviations
    BP = blood pressure
    DBP = diastolic blood pressure
    MI = myocardial infarction
    SBP = systolic blood pressure
    Reference
    Neaton JD, Kuller L, Stamler J, et al. Impact of systolic and diastolic blood pressure on cardiovascular mortality. In: Laragh JH, Brenner BM, editors. Hypertension: pathophysiology, diagnosis and management. 2nd ed. New York: Raven Press Ltd., 1995. p. 127–44.
  • Hypertension is a risk factor for coronary heart disease (CHD); the relative risk of CHD mortality increases markedly with increasing blood pressure.
    In a study of &gt;340,000 men without previous myocardial infarction (MI), elevated systolic blood pressure (SBP) was associated with a greater likelihood of death from CHD, with relative risk rates more than doubling when SBP rose from 140–159 to 180–209 mmHg, and a relative risk of 6.4 associated with a SBP of ≥210 mmHg.
    There was also an increase in relative risk with rising DBP. In patients with a DBP of 100–109, the relative risk more than doubled; in those with a DBP of ≥120, the risk rate is 5.17.
    Abbreviations
    BP = blood pressure
    CHD = coronary heart disease
    DBP = diastolic blood pressure
    MI = myocardial infarction
    SBP = systolic blood pressure
    Reference
    Neaton JD, Kuller L, Stamler J, et al. Impact of systolic and diastolic blood pressure on cardiovascular mortality. In: Laragh JH, Brenner BM, editors. Hypertension: pathophysiology, diagnosis and management. 2nd ed. New York: Raven Press Ltd., 1995. p. 127–44.
  • Abbreviations
    BP = blood pressure
    ESRD = end-stage renal disease
    MRFIT = Multiple Risk Factor Intervention trial
    Reference
    Klag MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med 1996;334:13–18.
  • Slide 4
    High-normal blood pressure (BP) is associated with an increased risk for cardiovascular disease (CVD).
    The association between baseline BP and the incidence of CVD on follow-up was investigated in 6859 participants in the Framingham Heart Study who were initially free of hypertension and CVD [Vasan et al, 2001]A stepwise increase in cardiovascular (CV) event rates was noted in subjects with higher baseline BP levels. The 10-year cumulative incidence of CVD in subjects aged 35 to 64 years with high-normal BP at baseline (systolic BP: 130-139 mm Hg; diastolic BP: 85-89 mm Hg) was 4% in women and 8% in men. In older subjects (aged 65 to 90 years), the CV incidence was 18% in women and 25% in men. Compared with optimal BP, high-normal BP was associated with a risk factor-adjusted hazards ratio of 2.5 in women and 1.6 in men.
  • Slide 6
    Reductions in the population distribution of diastolic blood pressure (DBP) could have a great impact on public health, in terms of the incidence of coronary heart disease (CHD) and stroke, including transient ischemic attacks (TIAs). Even DBP reductions as small as 2 mm Hg could have significant effects on the incidence of CHD and stroke.
    Published data from the Framingham Heart Study, a longitudinal cohort study, and the second National Health and Nutrition Examination Survey (NHANES II), a national population survey, were used to examine the impact of a population-wide strategy aimed at reducing DBP by an average of 2mm Hg (Cook el al, 1995)Participants included white men and women aged 35 to 64 years residing in the United States. A small reduction of 2mm Hg in DBP was associated with a 6% reduction in the risk of CHD and a 15% reduction in the risk of stoke and TIA.
  • Slide 8
    In patients with diabetes, tight blood pressure (BP) control appears to provide a greater reduction in the risk of macro vascular disease, including stroke and cardiovascular (CV) death, than does intensive blood glucose control.
    The primary goal of the UKPDS (United Kingdom Prospective Diabetes Study) was to determine the effect of intensive blood glucose control vs. conventional treatment on macro vascular and micro vascular complications in 3867 newly diagnosed subjects with type 2 diabetes [UKPDS, 1998a].Embedded within the UKPDS was a randomized trial comparing tight BP control in the hypertensive subgroup of enrolled diabetic subjects (n=1148) [UKPDS, 1998b]Although intensive blood glucose control significantly reduced the risk for micro vascular endpoints, such as retinal photocoagulation, tight BP control also significantly reduced the risk for micro vascular and macro vascular complications, including stroke and diabetes-related deaths (two thirds of which were due to CV disease). Captopril- and atenolol-based regimens were equally effective in reducing BP and in reducing the risk for macro vascular and micro vascular complications of type 2 diabetes [UKPDS, 1998c]
  • Major clinical trials have demonstrated that patients typically needed treatment with multiple antihypertensive agents to get to, and stay at, BP goal.
    The number of antihypertensive agents required for BP control in many patients typically averages 24, with co-morbid conditions (such as kidney disease or diabetes mellitus) imposing greater drug requirement.1
    For example, in the Hypertension Optimal Treatment (HOT) study, an average of 3.3 drugs were required to attain a diastolic BP goal of &lt;80 mmHg, and in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), most patients were taking at least two antihypertensive agents by the end of the trial.1,2
    References
    1. Bakris GL, et al. The importance of blood pressure control in the patient with diabetes. Am J Med 2004;116(5A):30S–8S.
    2. Dahlöf B, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005;366:895906.
  • Figure 57 Not much genetic evolution has occurred in humans in the past 20,000 years. In the Palaeolithic age, our ‘thrifty genotype’ was well-adapted to the high level of physical activity associated with our hunter-gatherer existence. However, this genotype has become redundant in the presence of our sedentary lifestyle and a diet low in fibre and high in animal fats and glucides. In short, our genotype – no longer adapted to our lifestyle – has become a ‘susceptibility genotype’.
  • This slide shows an obvious example of a lost opportunity to stimulate our cardiovascular system and to burn a few calories by taking the stairs rather than the elevator. Many of these lost opportunities can be compiled throughout the day. It is thus very easy to figure out how much our energy expenditure has decreased in our daily lives.
    While we are exposed to a “toxic” food environment, our lives are simply too comfortable. The energy density of food is unfortunately very high. This can be largely explained by the high fat and/or sugar content of the refined diet that we consume.
  • Therefore, the introduction of the National Cholesterol Education Program-Adult Treatment Panel III guidelines, which proposes the measurement of waist circumference, has been a major contribution and a giant conceptual leap.
    Waist circumference should be measured in every single patient. It is an important vital sign to identify the group of individuals likely to be carriers of the features of the metabolic syndrome.
  • Speaker’s Notes/Talking Points:
    Low high-density lipoprotein cholesterol (HDL-C) levels (&lt; 40 mg/dL) are associated with an increased risk of coronary heart disease (CHD) even if the total cholesterol (Total-C) level is &lt; 200 mg/dL. This slide shows the CHD incidence over 14 years among Framingham Study subjects who were aged 48–83 years at baseline.1 Among those with HDL-C levels &lt; 40 mg/dL and Total-C &lt; 200 mg/dL, 11.24% experienced a CHD event. This incidence was virtually the same as that (11.91%) for subjects with HDL-C levels between 40–49 mg/dL and Total-C  260 mg/dL.
    References
    1. Castelli WP, Garrison RJ, Wilson PW, et al. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study. JAMA. 1986;256:2835–2838.
  • Slide 10
    The 4S, LIPID and CARE trials demonstrated that long-term intervention with statins therapy reduces mortality and recurrent ischemic cardiovascular events in patients with stable coronary heart disease. The duration of follow-up of these studies was 5.4 years for 4S, 6.1 years for LIPID and 5.0 years for CARE. However, these trials excluded patients who had experienced unstable angina or acute MI within 3 to 6 months prior to randomization [8–10]. In fact, it is within the first few weeks to months following an acute coronary syndrome that patients experience the highest rate of death and recurrent ischemic events.
    To date, it has not been determined whether initiation of treatment with a statin immediately following an acute coronary syndrome can reduce the occurrence of these early events. The MIRACL study has been designed specifically to address this issue [14].
    References
    8. Scandinavian Simvastatin Survival Study Group. Lancet 1994;344:1383–1389.
    9. Sacks FM et al. N Engl J Med 1996;335:1001–1009.
    10. The long-term intervention with pravastatin in ischaemic disease (LIPID) study group. N Engl J Med 1998;339:1349–1357.
    14. Schwartz GG et al. Am J Cardiol 1998;81:578–581.
  • Figure 5 The diabetes epidemic is a major contributory factor to the increasing prevalence of AS and its worldwide prevalence will almost double by 2010. This is of particular importance in developing countries (e.g. those in South America, Africa, and Asia).
  • Slide 9. Survival Post-MI in Diabetic and Nondiabetic Men and Women: Minnesota Heart Survey
    In the Minnesota Heart Study, the case fatality rate after admission to the coronary care unit over 5 years was significantly higher in diabetic men than in nondiabetic men, and also in diabetic women relative to nondiabetic women. This analysis suggests that the case fatality rate may be higher in diabetic women than in diabetic men.
    Reference:
    Sprafka JM, Burke GL, Folsom AR, McGovern PG, Hahn LP. Trends in prevalence of diabetes mellitus in patients with myocardial infarction and effect of diabetes on survival: the Minnesota Heart Survey. Diabetes Care 1991;14:537-543.
    http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=1914792&amp;dopt=Abstract
    Keywords: diabetes, Minnesota Heart Survey, myocardial infarction
    Slide type: graph
  • Coronary Artery Disease in Epidemic Proportions in the Indian Subcontinent

    1. 1. {
    2. 2. Coronary Artery disease in an epidemic proportion in India: Risk Factors and their management Dr Javed Akhtar Consultant Cardiologist Clinical Lead, Cardiology Unit BHR NHS Trust, London Honorary senior Lecturer University of London
    3. 3. NOT ANGINA ANGINA ANGINA-Chest pain distribution
    4. 4. SOME FACTS ABOUT HEART DISEASE      82,000 die every year in UK due to CAD It is the leading cause of death for both men and women in the U.K Worldwide, coronary heart disease kills more than 7 million people each year Mortality in UK from CAD is decreasing significantly and a reduction in mortality of 40% has been achieved in a decade Mortality from CAD is not decreasing among the south Asians as fast as in white population
    5. 5. Atherosclerosis: When does it begin? 100 Prevalence of coronary atherosclerosis (%) 85% 80 71% 60% 60 37% 40 20 0 17% 13–19 20–29 30–39 Age (years) 40–49 ≥50 Data from 262 heart transplant donors. Sites with intimal thickness ≥0.5 mm were defined as atherosclerotic . Tuzcu EM, et al.. Circulation. 2001;103:2705-2710.
    6. 6. Atherosclerosis Timeline Foam Cells Complicated Fatty Intermediate Fibrous Lesion/ Streak Lesion Atheroma Plaque Rupture Endothelial Dysfunction From First Decade From Third Decade Adapted from Pepine CJ. Am J Cardiol. 1998;82(suppl 104). From Fourth Decade
    7. 7. Atherosclerosis is a Chronic Inflammatory Disorder
    8. 8. American Heart Association 10 Factors That Increase the Risk of Heart Disease and Heart Attack: 1) Diabetes Mellitus 2) Tobacco Smoke 3) High Blood Cholesterol 4) High Blood Pressure 5) Physical Inactivity 6) Obesity and Overweight 7) Stress 8) Alcohol 9) Diet and Nutrition 10) Age
    9. 9. Hypertension    Substantial Under-diagnosis Under-Treatment Poor Rates of BP control
    10. 10. High Blood Pressure strain on the heart
    11. 11. High Blood Pressure
    12. 12. Hypertension A Risk Factor for Cardiovascular Disease Coronary disease 50 Biennial ageadjusted rate per 1000 subjects Peripheral artery Cardiac Stroke disease failure 45.4 40 30 20 10 0 Risk ratio: Normotensive Hypertensive 22.7 21.3 9.5 12.4 3.3 Men Women 2.0 2.2 Kannel WB. JAMA. 1996;275:1571-1576. 2.4 6.2 Men Women 3.8 2.6 13.9 9.9 5.0 7.3 2.0 Men Women 2.0 3.7 3.5 6.3 2.1 Men Women 4.0 3.0
    13. 13. Increasing BP is closely associated with increasing risk of death from stroke Relative risk of stroke mortality 30 DBP 25 SBP 24.34 20 15 12.57 10 5 0 6.31 1.00 1.76 1.44 <80 85–89 80–84 2.54 6.57 4.00 100–109 ≥120 90–99 110–119 DBP (mmHg) RAS07000047 10.70 n=347,978 men without previous MI 1.00 1.68 2.33 3.78 <120 130–139 160–179 ≥210 120–129 140–159 180–209 SBP (mmHg) Neaton JD, et al. 1995
    14. 14. Increasing BP is closely associated with increasing risk of death from coronary heart disease Relative risk of CHD mortality 8 SBP 6 DBP 6.40 5.26 4 5.17 3.45 3.42 2.56 2.45 2 0 1.00 1.28 1.66 1.00 <120 130–139 160–179 ≥210 120–129 140–159 180–209 SBP (mmHg) n=347,978 men without previous MI CHD: coronary heart disease RAS07000047 1.48 1.21 <80 85–89 80–84 1.84 100–109 ≥120 90–99 110–119 DBP (mmHg) Neaton JD, et al. 1995
    15. 15. Increasing BP is closely associated with increasing risk of end stage renal disease Adjusted relative risk 25 * 22.1 20 15 * 11.2 10 * * * 5 3.1 140 159 90 99 1.0 1.2 1.9 80 <130 85 130 139 85 89 0 BP (mmHg) <120§ 6.0 160 179 100 109 180 209 110 119 ≥210 120 *p<0.001; ESRD due to any cause in 332,544 men screened for MRFIT § Men with optimal BP was the reference category RAS07000047 Klag MJ, et al. N Engl J Med 1996
    16. 16. Impact of High-Normal BP on CV Risk 16 Cumulative incidence of CV events (%) High-normal BP Men 14 12 10 Normal BP 8 6 4 2 Optimal BP 0 { 12 Cumulative incidence of CV events (%) Women 10 High-normal BP 8 6 Normal BP 4 2 Optimal BP 0 0 2 4 6 Years 8 10 12 Optimal BP: <120/80 mm Hg; normal BP: 120-129/80-84 mm Hg; high-normal BP: 130139/85-89 mm Hg. Vasan RS et al. N Engl J Med. 2001;345:1291-1297.
    17. 17. Implications of Small Reductions in DBP for Primary Prevention DBP reduction 0 7.5 mm Hg 5-6 mm Hg -6 -10 -20 Risk reduction -30 (%) -15 -16 -21 -40 -50 2 mm Hg -38 -46 CHD, coronary heart disease. Cook NR et al. Arch Intern Med. 1995;155:701-709. CHD Stroke
    18. 18. Benefits of Tight BP and Tight Glucose Control UKPDS 0 Stroke Any diabetes- Microvascular Diabetes-related endpoints related endpoint deaths -10 † -20 Risk reduction -30 (%) -40 -50 * † * * * Tight glucose control Tight BP control *P<0.02, tight BP control (achieved BP 144/82 mm Hg) vs.. less tight control (achieved BP 154/87 mm Hg). † P<0.03, intensive glucose control (achieved HbA 1c 7.0%) vs. less intensive control (achieved HbA1c 7.9%). UKPDS Group. BMJ. 1998;317:703-713. UKPDS Group. Lancet. 1998;352:837-853.
    19. 19. Risk associated with LVH secondary to Hypertension LVH is a major risk factor for CVD 1-6 fold higher risk for angina 2-5 fold higher risk for MI 6-17 fold higher risk for heart failure 3-10 fold higher risk for stroke
    20. 20. Management of Hypertension Drugs 1. ACE-inhibitor/ARBs 2. Calcium Channel Blocker: Amlodipine/Felodipine 3. Diuretic: Bendroflumethiazide 4. . Spironolactone 5. Beta-blocker  Non-Pharmacological interventions: 1. Reduction in body weight 2. Regular exercise 3. Reduction in salt intake 4. Regular life style 
    21. 21. Why do so many patients fail to achieve BP goal?          Poor compliance Ineffective drugs Occasional missed doses Asymptomatic condition Lifestyle factors Drug side-effects Need for additional agents Key Reason for poor BP control is use of Monotherapy Majority of patients require two or more drugs
    22. 22. Multiple antihypertensive agents are needed to reach BP goal Trial (SBP achieved) ASCOT-BPLA (136.9 mmHg) ALLHAT (138 mmHg) IDNT (138 mmHg) RENAAL (141 mmHg) UKPDS (144 mmHg) ABCD (132 mmHg) MDRD (132 mmHg) HOT (138 mmHg) AASK (128 mmHg) 1 2 3 4 Average no. of antihypertensive medication s RAS07000047 Adapted from Bakris et al. Am J Med 2004;116(5A):30S–8 Dahlöf et al. Lancet 2005;366:895–906
    23. 23. Hypertension  The single most important aspect of treating a patient with Hypertension is to achieve Optimal Blood Pressure and treating the other risk factors simultaneously
    24. 24. Hypertension Life Style Advice Reduce Body weight (Maintain BMI 20-25 Kg/m2)  Reduce dietary Sodium Intake to <100 mmol/day or 6 G of Nacl or 2.4 G of Na/day  Regular Aerobic Exercise(brisk walking 30 mt/day , most of the days)  Limit Alcohol consumption  Quit Smoking  Reduce dietary intake of saturated fat and increase Vegetables and Fruit portions 
    25. 25. Wrong Dietary Habits
    26. 26. Certain Facts about South Asians  Diet high in fat and low in fruits & vegetables
    27. 27. Certain Facts about South Asians  Simply a cultural difference? 200g Margarine 2 Kilos Ghee!
    28. 28. Stress related Heart disease
    29. 29. Lack of Exercise
    30. 30. Genes and environment in type 2 diabetes and atherosclerosis
    31. 31. Waist circumference as a measure of body fat distribution Women >80 cm = Increased risk cm Men >88 cm = Increased risk Lean MEJ et al. Lancet; 1998; 351:853-6
    32. 32. Waist Circumference A VITAL SIGN!!!
    33. 33. SMOKING
    34. 34. Certain Facts about South Asians  Smoke more than others
    35. 35. Harmful Chemicals in Cigarettes:      >4,000 chemicals inside a cigarette The two most harmful chemicals are: Nicotine and carbon monoxide Nicotine: causes addiction, speeds up the heart, raises blood pressure, and constricts the arteries Carbon monoxide: robs the heart of oxygen, and when combined with nicotine it increases blood clotting and clogging
    36. 36. Smoking People who smoke:      High risk for IHD High Blood pressure Heart attacks COPD/Chronic bronchitis Lung Cancer and other adverse effects
    37. 37. Smoking: Some facts      10 Million People smoke in England 120,000 deaths in UK are Smoking related 50% of Smokers will die prematurely 1 in 2 of those who die , die before they reach middle age. 20% of CHD related deaths in men and 17% in women are attributed to Smoking
    38. 38. Smoking: Some facts  Smoking 3-6 Cigs/day doubles the chance of having Heart attack  Smokers are > twice likely to have fatal heart attack than non-Smokers  Within 5 years of giving up smoking risk is reduced almost to that of nonsmoker
    39. 39. Non-Smoker’s Lungs
    40. 40. Smoker’s Lungs
    41. 41. Hyperlipidaemia
    42. 42. Do Statins do more than lower lipids? Apart from lowering Total Cholesterol, LDL and Triglycerides, and slight increase in HDL, they also have following functions: 1. Fall in C-reactive protein 2. Statins bind to the lymphocyte function-associated antigen1(LFA-1) therefore potent anti-inflammatory effects 3. Statins improve endothelial function by increasing nitric oxide, a vasodilator and decreases the production of endothelin-1, a potent vasoconstrictor 4. Statins increase the number and activity of circulating progenitor cells in patients with stable coronary artery disease which may promote the growth of collateral circulation
    43. 43. % reduction LDL cholesterol Correlation between percent reduction of LDL cholesterol and percent reduction of CAD mortality - 60% ? Secondary prevention Primary prevention 4S LIPID - 30% CARE Post-CABG AFCAPS WOSCOPS 0 0 - 35% % reduction CAD mortality - 70%
    44. 44. % reduction CAD morbidity Correlation between absolute reduction of LDL cholesterol and percent reduction of CAD morbidity 25 Secondary CAD prevention Primary CAD prevention 4S-Pl 20 4S-Rx LIPID-Pl 15 CARE-Pl CARE-Rx WOS-Pl LIPID-Rx 10 TNT: Atorva 10 mg WOS-Rx AFCAPS-Pl TNT: Atorva 80 mg 5 AFCAPS-RX 0 50 70 90 110 130 150 LDL cholesterol mg/dl 170 190 210
    45. 45. Low HDL-C Levels Increase CHD Risk Even When Total-C Is Normal (Framingham) .91 11 .24 11 5 9.0 .7 10 6.6 3 5.5 6 6.5 3 3.8 5 4.8 5 4.1 7 3.7 ≥ 6.5 6.0-6.5 5.0-6.0 < 5.0 6 2.0 8 2.7 < 1 1-1.2 1.2-1.5 ≥ 1.5 HDL-C (mmol/L) Risk of CHD by HDL-C and Total-C levels; aged 48–83 y Castelli WP et al. JAMA 1986;256:2835–2838 (m m ol /L ) 7 4.6 l-C 14 12 10 8 6 4 2 0 .91 11 To ta 14-y incidence rates (%) for CHD .50 12
    46. 46. MIRACL: Addressed a Research Gap Acute coronary event No history of CAD Unstable CAD Stable CAD 4 mo AFCAPS / TexCAPS/ WOSCOPS MIRACL t=0 CARE/LIPID 3 mo 4S 6 mo Randomization: 24–96 h Primary prevention Randomization: CARE - 3–20 mo LIPID - 3–36 mo Randomization: >6 mo Secondary prevention Schwartz GG et al. Am J Cardiol 1998;81:578–581.
    47. 47. ASCOT-LLA  The prevention of coronary and stroke events with Atorvastatin in: Hypertensive patient with at least 3 CV risk factors, who have average or lower-than average cholesterol concentrations  Possible CV risk factors: LVH  Type II diabetes  PVD  H/o Stroke/TIA  Male >55 years old  Micro-albuminuria or Proteinuria  Smoking  premature family history of CHD A multicentre randomised placebo-controlled trial  Planned follow-up was 5 years, but trial was stopped after median 3.3 years after significant benefit with Atorvastatin emerged Sever PS et al. Lancet 2003; 361: 1149-1158 
    48. 48. Study design CCB = Calcium channel blocker ACEI = ACE inhibitor TC = Total cholesterol R 9,000 9,000 β-blocker ± diuretic β-blocker ± diuretic β-blocker ± diuretic β-blocker ± diuretic 5,000 5,000 TC ≤6.5 mmol/L TC ≤6.5 mmol/L ≤6.5 mmol/L TC ≤6.5 mmol/L TC R 2,250 2,250 atorvastati atorvastati atorvastati atorvastati n n n n R = Randomised ASCOT patients 18,000 patients ASCOT patients 18,000 4,000 4,000 TC >6.5 mmol/L TC >6.5 mmol/L >6.5 mmol/L TC >6.5 mmol/L TC 500 500 open lipid-lowering open lipid-lowering 2,250 2,250 placebo placebo placebo placebo + 9,000 9,000 CCB ± ACEI CCB ± ACEI CB ± ACEI CB ± ACEI 4,000 4,000 TC >6.5 mmol/L TC >6.5 mmol/L >6.5 mmol/L TC >6.5 mmol/L TC 500 500 open lipid-lowering open lipid-lowering 8,000 8,000 open lipid-lowering open lipid-lowering lipid-lowering open lipid-lowering open Adapted from Sever PS et al. for the ASCOT Investigators. J Hypertens 2001; 19: 1139-1147 2,250 2,250 placebo placebo placebo placebo 5,000 5,000 TC ≤6.5 mmol/L TC ≤6.5 mmol/L ≤6.5 mmol/L TC ≤6.5 mmol/L TC R 2,250 2,250 atorvastatin atorvastatin atorvastatin atorvastatin
    49. 49. Primary endpoint: Cumulative incidence of non-fatal MI & fatal CHD Atorvastatin 10 mg Proportion of patients % 100 Placebo 4 Number of events Number of events 154 3 36% Relative Risk Reduction 2 1 HR=0.64 (0.50-0.83) P=0.0005 0 0.0 0.5 1.0 1.5 2.0 Time (years) Adapted from Sever PS et al. Lancet 2003; 361: 1149-1158 2.5 3.0 3.5
    50. 50. Cumulative incidence for fatal & non-fatal stroke Atorvastatin 10 mg Proportion of patients (%) Number of events 89 Placebo 3 Number of events 121 27% Relative Risk Reduction 2 HR=0.73 (0.56-0.96) P=0.0236 1 0 0.0 0.5 1.0 1.5 2.0 Years Adapted from Sever PS et al. Lancet 2003; 361: 1149-1158 2.5 3.0 3.5
    51. 51. Effect of atorvastatin & placebo on study endpoints Primary Endpoints Non-fatal MI (incl silent) + fatal CHD Secondary Endpoints Total CV events and procedures Total coronary events Non-fatal MI (excl silent) + fatal CHD All-cause mortality Cardiovascular mortality Fatal and non-fatal stroke Fatal and non-fatal heart failure Tertiary Endpoints Silent MI Unstable angina Chronic stable angina Peripheral arterial disease Development of diabetes mellitus Development of renal impairment 0.64 (0.50-0.83) 0.5 Placebo better 1.0 1.5 0.0005 0.79 (0.69-0.90) 0.71 (0.59-0.86) 0.62 (0.47-0.81) 0.87 (0.71-1.06) 0.90 (0.66-1.23) 0.73 (0.56-0.96) 1.13 (0.73-1.78) Atorvastatin better Adapted from Sever PS et al. Lancet 2003; 361: 1149-1158 Hazard Ratio (95% CI) P value Risk Ratio 0.0005 0.0005 0.0005 0.1649 0.5066 0.0236 0.5794 0.82 (0.40-1.66) 0.87 (0.49-1.57) 0.59 (0.38-0.90) 1.02 (0.66-1.57) 1.15 (0.91-1.44) 1.29 (0.76-2.19) 0.5813 0.6447 0.0135 0.9254 0.2493 0.3513 Area of squares is proportional to the amount of statistical information
    52. 52. Summary Primary endpoint : Treatment with atorvastatin 10 mg/day (vs placebo) in hypertensive patients with multiple risk factors is associated with: Significant risk reductions in   Total coronary events (-29%, P=0.0005)   Total cardiovascular events and procedures (-21%, P=0.0005)   Non-fatal MI (inc. silent MI) & fatal CHD (-36%, P=0.0005) [Primary endpoint] Fatal and non-fatal stroke (-27%, P=0.0236) These reductions in major CV events are large given the short follow-up time (median 3.3 years, after 5 year study was stopped early) These endpoints were met despite patients having average or lower than average baseline cholesterol levels Sever PS et al. Lancet 2003; 361: 1149-1158
    53. 53. Conclusion In hypertensive patients with multiple risk factors at modest risk of CHD, with average or lower than average cholesterol concentrations, atorvastatin is associated with significant risk reductions in major CV events including stroke Sever PS et al. Lancet 2003; 361: 1149-1158
    54. 54. Diabetes: Is it coronary equivalent?
    55. 55. Global projections for the diabetes epidemic 1995-2010
    56. 56. Diabetes Risk factors for developing Diabetes:  Obesity  Lack of Exercise  sedentary life style  Waist girth increase  Family history of diabetes  increasing age
    57. 57. So WHO is at risk ? Diabetes - a Major CHD Risk Factor 40 7 year follow-up Incidence of MI after 50 30 20 10 0 Normal Prior M I Type 2 Population (no diabetes) Diabetes (without M I) Type 2 Diabetes (prior M I) “ … all persons with diabetes could be treated as if they had prior coronary heart disease.” 1. Haffner SM et al N Engl J Med 1998; 339: 229-234
    58. 58. Survival Post-MI in Diabetic and Non-diabetic Men and Women: Minnesota Heart Survey 100 MEN 100 n=1628 80 60 Diabetes n=228 40 0 0 20 40 60 Months Post-MI 80 No diabetes Survival (%) Survival (%) No diabetes WOMEN 80 n=568 60 Diabetes 40 0 0 n=156 20 40 60 80 Months Post-MI Adapted from Sprafka JM et al. Diabetes Care 1991;14:537-543.
    59. 59. Diabetes and CVD In people with diabetes: 1. Heart disease twice as often as people without diabetes. 2. CVS complications occur at an earlier age and result in premature death. 3. Diabetics are 2-4 times more likely to suffer strokes if had a stroke, 2-4 times as likely to have a recurrence.
    60. 60. Insulin Resistance
    61. 61. The RIGHT drug for the RIGHT patient This profile could be BADNEWS for patients with the Metabolic Syndrome and/or type 2 diabetes … as they may be at serious risk of CHD due to their low HDL See Slide 28 for Prescribing Information
    62. 62. Insulin resistance is linked to a range of CVD risk factors Insulin resistance Endothelial dysfunction Hypertension Dyslipidaemia Microalbuminuria Vascular inflammation Atherosclerosis CVD Adapted from McFarlane SI, et al. J Clin Endocrinol Metab 2001;86:713–718.
    63. 63. Proportion of patients with cardiovascular disease increases with duration of type 2 diabetes 48% 29% 21% 24% 15% <=2 3-5 6-9 10-14 15+ Years T2DM Harris,S et al. CDA 2003; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load.
    64. 64. Investigations in suspected coronary artery disease
    65. 65. Investigating suspected coronary artery disease Blood tests: FBC, U&E, FBS, Fasting lipids, GTT CXR ECG Echocardiography Non-invasive tests: 1. Treadmill ECG stress test 2. Myocardial perfusion Imaging 3. Stress Echocardiography 4. CMR stress test 5. Calcium scoring and CT coronary angiography Coronary angiography Any other test for co-morbidities
    66. 66. Echocardiography
    67. 67. Normal chocardiography
    68. 68. Antero-septal MI
    69. 69. Antero-septal MI
    70. 70. Anterior MI
    71. 71. Anterior MI
    72. 72. Treadmill Test (Exercise ECG teat)
    73. 73. Stress Thallium Test
    74. 74. Severe coronary artery disease
    75. 75. Lt Main coronary stenosis LMCA stenosis RAO caudal.avi.mp4
    76. 76. Initial Treatment  A = Aspirin and Antianginal therapy  B = Beta-blocker and Blood pressure  C = Cigarette smoking and Cholesterol  D = Diet and Diabetes  E = Education and Exercise 80 medslides.com 1/00
    77. 77. Revascularization for Chronic Stable Angina coronary artery bypass surgery - Class I  significant left main disease (>60%)  3-vessel disease with LVEF< 50%)  Left Main equivalent 2-vessel disease with significant proximal LAD disease (>70%) and either LVEF < 50%) or 81  demonstrable ischemia on noninvasive testing medslides.com 1/00
    78. 78. Revascularization for Chronic Stable Angina  in patients with prior PCI, CABG or PCI or CABG - Class I PCI with a large area of viable myocardium and/or high-risk criteria on noninvasive testing  Failed Medical therapy 82 medslides.com 1/00
    79. 79. Severe coronary artery disease
    80. 80. PCI to LAD
    81. 81. Severe LAD stenosis before D1
    82. 82. PCI and ACS 50 yr old man, ST dep anterior leads, trop +ve Case 1
    83. 83. Coronary Artery Bypass Graft
    84. 84. Coronary Artery Bypass Graft
    85. 85. Exercise Daily exercise for 30 Mins
    86. 86. Exercise
    87. 87. Take-Home Message             Be aware of health issues Body weight Regular exercise Dietary habits: More vegetable and less meat, less oil/butter/Ghee About risk factors for CHD BP check up at regular intervals Strict control of Hypertension Strict control of diabetes >40 years, have at least ETT if possible even without any angina Strict control of dyslipidaemia(HDL, LDL, Total Cholesterol, Triglycerides level) If coronary artery disease be under follow-up of a properly trained cardiologist If you are advised PCI/CABG, discuss with the cardiologist pros and cons of the procedure and if it is going to increase your survival (it is not against Qaza-o-Kadr)
    88. 88. Thanks Dr Javed Akhtar

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