This Slideshow we will be discussing about Cardiovascular disease and how it is a leading cause of death. For more information please visit http://www.simplyweight.co.uk Articles http://www.simplyweight.co.uk/articles/ Videos http://www.simplyweight.co.uk/video/ Blogs http://simplyweight.co.uk/blogs/ Forum http://www.simplyweight.co.uk/forum/forum.php Contact Us http://www.simplyweight.co.uk/how-to-contact-us/

1. Managing High Risk Patients

2. Conclusions
• Cardiovascular disease is leading cause of death
• Cardiometabolic risk is:
– ‘All metabolic and vascular risk factors for CVD’
– Strongly enhanced by abdominal obesity, Type 2
diabetes and insulin resistance
– Occurring earlier and more commonly
– At least partially preventable or reversible
– Especially reduced by loss of excess visceral fat
– A priority for early identification and effective
management to delay onset of morbidity and reduce
premature mortality

3. Deaths attributed to CVD in Type 2 diabetes
Department of Health Statistics for England, 2002.
World Health Organization. Integrated Management of Cardiovascular Risk. 2002.
100
80
60
40
20
0
All M F All M F
CVD
mortality
%
Premature CVD is main cause of death in Type 2 diabetes
General
population
Diabetes
75
57
38.5 40.4
RIM06/413Date of preparation: August 2006
100
80
60
40
20
0
CVD
mortality
%
40.4

4. The Cardiovascular Disease Challenge
• In 2007, cardiovascular
disease (CVD) caused
34% of deaths in the
UK, and killed just over
193,000 people1
• CVD cost the health
care system in the UK
around £14.4 billion in
20062
• Overall CVD is
estimated to cost the
UK economy £30.7
billion a year of which
27% is due to
productivity losses2
Nationally Customer Actions Taken
• NSF for Cardiovascular Disease published in
1999
• Huge investment in waiting list reduction for
CABG and PTCA
• Multiple and detailed risk modification guidelines
including the role of statins
• Significant investment in lipid modification per
annum (c. £500m per annum)3
• Establishment of Stroke and Cardiac networks to
drive best practice and NSF implementation
• Significant investment in stop smoking services
NOTE:
For every one fatality, there are at least two people
who have a major non-fatal cardiovascular event.
There are over 3 million people living with coronary
heart disease or stroke.4
Inpatient cases for CVD across England in 2008/9
were 538,4595
1. http://www.heartstats.org/topic.asp?id=17
2. http://www.heartstats.org/datapage.asp?id=101
3. http://www.productivity.nhs.uk Render Report
4. NICE CG67 Lipid Modification Clinical Guidelines
http://www.nice.org.uk/nicemedia/live/11982/40689/40689.pdf Accessed June 2010
5. http://www.hesonline.nhs.uk Inpatients 2008-9

5. 1. Obesity
2. Hypertension
3. Lipids
4. Hyperglycaemia
5. Smoking

6. Dealing with CVD requires addressing two areas
Managing Modifiable
Risk Factors
Treating events
and their impact
1
2
• Diet
• Exercise
• Smoking
• Hypertension
• Lipid management
• Angiography
• PTCA
• CABG
• Thrombolysis
• Anti-coagulation
• Follow-up
– Up to 90% of the risk of a first heart attack is
due to lifestyle factors that can be changed1
– The Care Quality Commission study ‘Closing
the gap’1
highlights the lack of CVD
prevention.
– NICE Primary prevention of CVD2
• Strategy for identifying people at high
risk
• Full formal risk assessment for those at
high risk
• Communication about risk assessment
and treatment
• Optimisation of all modifiable risk
factors
• Lipid modification therapy
 To deliver more of the potential savings,
better performance in managing modifiable
risk factors to prevent patients from requiring
secondary care intervention
Closing the Gap – Tackling Cardiovascular Disease and health inequalities by prescribing statins and stop smoking services, Care Quality Commission, Sept. 2009
http://www.cqc.org.uk/_db/_documents/Closing_the_gap.pdf Accessed June 2010
NICE CG67 – Lipid Modification – Implementing NICE Guidance, March 2010 http://www.nice.org.uk/nicemedia/live/11982/40836/40836.ppt Accessed June 2010

7. Risk factors to address in the future
CARDIOVASCULAR DISEASE
Classical risk factors Emerging risk factors
Abdominal
obesity
↓HDL-C
↑TG
↑TNFα,IL-6
↑PAI-1
↑Glu
↑IR
T2DM
↑Smoking↑ LDL-C ↑ BP
↓ Adipo-
nectin
RIM06/413Date of preparation: August 2006

8. Current cardiometabolic risk
management approaches
• Anti-diabetic agents
– Metformin
– Sulphonylureas
– Glitazones
• Lipid modifying agents
– Statins
– Fibrates
– Nicotinic acid
• Antihypertensive agents
– ACE inhibitors
– Angiotensin II receptor antagonists
• Weight loss agents
– Orlistat

9. Obesity

10. Prevalence of adult obesity (BMI >30) in England
0
10
1980
20
30
1986 1991 1996 2000 2010
Prevalence(%)
Men
Women
Kopelman PG. Nature 2000; 404: 635–643; Health Survey for England, 2004; National Audit Office, February
2001; Select Committee on Public Accounts (9th Report), January 2002.
% overweight has stayed approx constant since 1993 (M~44%, F~33%)
Obesity causes ~30,000 premature deaths annually; 18 million lost working days in 1998
Cost to the nation (including the NHS) > £2.5 billion
England 2004
Overweight Obese
BMI 25–30 BMI >30
Men 44% 22%
Women 34% 23%
2004
RIM06/413Date of preparation: August 2006

11. Thou seest I have more flesh than
another man, and therefore more frailty.
William Shakespeare

12. Abdominal obesity: a major underlying
cause of acute myocardial infarction (MI)
Populationattributablerisk(%)*
* Proportion of MI in the total population attributable to a specific risk factor
Cardiometabolic risk factors in the INTERHEART study
0
20
40
60
Hypertension DiabetesAbdominal
obesity
Dyslipidaemia
Abdominal obesity predicts the risk of CVD
beyond body mass index (BMI)
18
10
20
49
Yusuf S, et al. Lancet 2004; 364: 937–952.
RIM06/413Date of preparation: August 2006

13. Question: does a waist circumference value of 102 cm and
88 cm distinguish health risk within BMI categories?
<88> <102>
RIM06/413Date of preparation: August 2006

14. Metabolic variables in women with low (<88 cm) versus
high (>88 cm) waist circumference values
Normal weight Overweight Obese
Low WC High WC Low WC High WC Low WC High WC
Fasting glucose 88 100* 90 100* 84 101*
LDL-cholesterol 113 137* 121 139* 118 136*
HDL-cholesterol 59 57* 54 54* 58 51*
NO DIFFERENCE
(n=2959) (n =469) (n =741) (n =1865) (n=38) (n=1467)
Triglycerides 97 152* 120 158* 104 161*
Systolic BP 115 129* 117 128* 116 128*
NHANESIII
Janssen I, et al. Arch Intern Med 2002; 162: 2017–2079.
RIM06/413Date of preparation: August 2006

15. Abdominal obesity, morbidity and mortality
Intra-abdominal fat is a
strong correlate of metabolic risk
Intra-abdominal or
visceral fat
INSIDE
Intra-abdominal Fat
OUTSIDE
Waist Circumference
RIM06/413Date of preparation: August 2006

16. Visceral fat is an independent
predictor of
all-cause mortality in 291 men
followed for 5 years
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Visceral Fat Subcutaneous
Fat
Waist
Circumference
CTL/CTS
OddsRatiosforMortality
Model 2: Control for age, follow-up time,
abdominal subcutaneous fat, visceral
fat and liver fat
Model 1: Control for age + follow-up time
1.8 1.4 1.4 0.8
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Visceral Fat Subcutaneous
Fat
Waist
Circumference
CTL/CTS
OddsRatiosforMortality
1.8 1.0 0.6 1.3
An 0.37 kg increase in visceral fat is
associated with 81% higher mortality
after control for SAT and liver fat
Kuk JL, et al. Obes Res 2006 14: 336–341. RIM06/413Date of preparation: August 2006

17. Reduction in abdominal subcutaneous and visceral fat inReduction in abdominal subcutaneous and visceral fat in
response to aresponse to a 7%7% exercise-induced weight loss,exercise-induced weight loss, 66 cm reduction incm reduction in
waist circumferencewaist circumference
Adapted from Ross R,Adapted from Ross R, et alet al.. Ann Intern MedAnn Intern Med 2001;2001;Obes ResObes Res 2004;2004; 1212: 789–798.: 789–798.
MENMEN WOMENWOMEN
0
10
20
30
Reduction(%)Reduction(%)
ControlControl ExerciseExercise
**
**
0
10
20
30
Reduction(%)Reduction(%)
ControlControl ExerciseExercise
**
**
Visceral fat
Subcutaneous fat
**p< 0.05 vs controlp< 0.05 vs control
RIM06/413Date of preparation: August 2006
~5% decrease in waist
circumference
corresponds to a ~30%
decrease in visceral fat!

18. Potential benefits of 10kg weight
loss in individuals of 100kg

19. Lipids

20. 20
•Offer statin treatment as part of PRIMARY PREVENTION for adults with a
10 year risk of 20%.
•Treat with simvastatin 40 mg. If this is contraindicated or drug interactions
are possible, choose a lower dose or an alternative such as Atorvastatin.
•Do not routinely offer higher intensity statins—that is,
statins used in doses producing greater cholesterol lowering than
simvastatin 40 mg (for example, simvastatin 80 mg).
[No randomised controlled trials have compared high and low intensity statins in relation to
cardiovascular outcomes in people without cardiovascular disease]

21. Substantial residual CV risk in statin-treated
patients
Year of follow-up
Patientswithmajor
vascularevents(%)
The MRC/BHF Heart Protection Study
Placebo
Risk reduction=24%
Statin
Heart Protection Study Collaborative Group. Lancet 2002; 360: 7–22.
BHF=British Heart Foundation
MRC=Medical Research Council
10
20
30
0
0 1 2 3 4 5 6
19.8% of statin-treated
patients had a major
CV event by 5 years
p<0.0001
RIM06/413Date of preparation: August 2006

22. 22
•Use the estimated risk value to prioritise patients, and
arrange a full formal risk assessment for patients whose
estimated 10 year risk is 20%.
•Assess risk using the 1991 Framingham 10 year risk
equations, with the following variables:
1. Age (30-74 years)
2. Sex
3. Systolic BP
4. TC
5. HDL
6. Smoking status
7. LVH

23. 23
•Fasting lipid levels are not needed for risk assessment.
•Record factors important for development of
CV disease, such as ethnicity, BMI and F/H of
premature heart disease.
•Adjust the risk score for factors important for
development of CV disease but not

24. included in the risk score as follows:
•If there is one first degree relative with premature
coronary heart disease,
increase the estimate by 1.5;
•if there is more than one first degree relative with
premature coronary heart disease,
increase the estimate by up to 2
•Increase the estimated risk for men with a South Asian
background by 1.4.

25. •Do not set a target concentration for total or LDL
cholesterol in primary
prevention.
•Once a patient has started taking a statin, repeat lipid
measurement is unnecessary.
Clinical judgment and the patient’s preference should guide
the review of drug treatment
and whether to review the lipid profile.

26. 26
Statins for secondary prevention
Consider all modifiable risk factors, comorbidities, and
secondary causes of hyperlipidaemia, and optimise their
management.
Offer statin treatment to adults with clinical evidence of CV
disease.3
Start treatment with simvastatin 40 mg. If there are
potential drug interactions, or simvastatin 40 mg is
contraindicated, choose a lower dose or an alternative
preparation such as pravastatin.
Offer people with acute coronary syndrome a higher intensity
statin. [Based on results of health economic modelling of cost
effectiveness]

27. 27
Consider increasing the dose to simvastatin 80 mg or a drug of
similar efficacy and acquisition cost if a total cholesterol
concentration of <4 mmol/l or a low density lipoprotein cholesterol
concentration of <2 mmol/l is not attained
Use an "audit" concentration of total cholesterol of 5 mmol/l to
assess progress in populations being treated for secondary
prevention, as more than half will not achieve a total cholesterol
concentration of <4 mmol/l or a low density lipoprotein cholesterol
concentration of <2 mmol/l

29. When generic statins aren’t enough, Atorvastatin has a
wealth of cardiovascular evidence
Atorvastatin has a wealth of published cardiovascular outcomes trials showing
significant primary endpoint benefits:
0Ezetimibe
0Ezetimibe/simvastatin
0Simvastatin 80mg
1Rosuvastatin
8Lipitor
Published CV outcomes
trials with significant
primary endpoint
benefit
Cholesterol-lowering
therapy Atorvastatin has 157 million patient years’
experience worldwide and has been
available in the UK for over 10 years
There are over 4 million patient-years’
experience worldwide at the 80 mg
dose
LINK: Quality and
Evidence

30. 30
•nicotinic acid
• Omacor
• bile acid sequestrants
•PPAR agonists
• CETP inhibitors
•HDL mimetics
•ApoA-I mimetic peptides
•HDL delipidation and reinfusion

31. 31
Difficult Hyperlipidaemia
Combined hyperlipidaemia
Isolated hypertriglyceridaemia
Hyperlipidaemia in pregnancy
Intolerance to anti lipid agents

32. In summary
Atorvastatin is the statin with
the largest evidence base,
showing it to be an effective
treatment in the
management of raised
cholesterol and provides a
proven reduction in
Cardiovascular events
Quality
Atorvastatin offers the
opportunity to make savings
now (vs. Ezetimibe) and
longer term through windfall
savings once it loses
exclusivity and there is a price
drop. Atorvastatin goes off
patent before the other
branded lipid lowering agents.
Productivity
Atorvastatin can help to
reduce cardiovascular
events by treating to NICE
recommended cholesterol
levels of 4:2 for diabetes,
CHD and stroke patients
leading to a productivity
gain through avoided
spending on events
Productivity

33. Diabetes

34. In Type 2 diabetes, elevated HbA1c
increases risk of complications
Stratton IM, et al. BMJ 2000; 321: 405–412.
Incidence rate for any end point related to
diabetes in males with Type 2 Diabetes
Effective glycaemic control is associated with reduced risk of
microvascular and macrovascular complications
5 6 7 8 9 10 110
0
20
40
60
80
100
120
140
160
Updated mean HbA1c concentration (%)
Adjustedincidenceper
1000personyears(%)
RIM06/413Date of preparation: August 2006

35. Hypertension

36. BHS classification of blood pressure levels
Category Systolic blood pressure
(mmHg)
Diastolic blood pressure
(mmHg)
Optimal BP <120 <80
Normal BP <130 <85
High-normal BP 130-139 85-89
Grade 1 hypertension (mild) 140-159 90-99
Grade 2 hypertension
(moderate)
160-179 100-109
Grade 3 hypertension
(severe)
>180 >110
Isolated systolic
hypertension (grade 1)
140-159 <90
Isolated systolic
hypertension (grade 2)
>160 <90
BHS IV. B Williams et al. J Hum Hyp (2004); 18: 139-185.

37.
Target organ damage
or
cardiovascular complications
or
diabetes
or
10 year CVD risk† ≥ 20%
>180/110 160−179
100−109
140−159
90−99
130−139
85−89
<130/85
≥160/100 140−159
90−99
<140/90
No target organ damage
and
no cardiovascular complications
and
no diabetes
and
10 year CVD risk† <20%
* ** ***
Treat Treat Treat Observe, reassess
CVD risk yearly
Reassess
yearly
Reassess
in 5 years
* Unless malignant phase of hypertensive emergency confirm over 1−2 weeks then treat
** If cardiovascular complications, target organ damage or diabetes is present, confirm over 3−4 weeks then treat; if absent re-measure
weekly and treat if blood pressure persists at these levels over 4−12
*** If cardiovascular complications, target organ damage, or diabetes is present, confirm over 12 weeks then treat: if absent re-measure
monthly and treat if these levels are maintained and if estimated 10 year CVD risk is ≥20%
† Assessed with CVD risk chart
THRESHOLDS FOR INTERVENTION
Initial blood pressure (mmHg)

38. Cardiovascular Risk – Non diabetic Men

39. Cardiovascular Risk – Non diabetic Women

40. The consequences of not treating hypertension
Stroke
Heart Attack
LVH
Renal disease
Atrial fibrillation
Diabetes

41. Lowering Blood Pressure Reduces CV Events
• The greatest impact (absolute numbers) from control of
hypertension occurs in men, older persons, and those
with isolated systolic hypertension.
• The greatest proportion of preventable CHD events from
control of hypertension occurs in women.
• Optimal control of blood pressure could prevent more
than one third of CHD events in men and more than half
of CHD events in women.
Wong et al. Am Heart J. 2003; 145: 888-895.

42. Lifestyle Measures
•Maintain normal weight for adults (body mass index 20-
25 kg/m2
)
•Reduce salt intake to <100 mmol/day (<6g NaCl or <2.4
g Na+
/day)
•Limit alcohol consumption to ≤3 units/day for men and
≤2 units/day for women
•Engage in regular aerobic physical exercise (brisk
walking rather than weight lifting) for ≥30 minutes per
day, ideally on most of days of the week but at least on
three days of the week
•Consume at least five portions/day of fresh fruit and
vegetables
•Reduce the intake of total and saturated fat
BHS IV. B Williams et al. J Hum Hyp (2004); 18: 139-185.

43. Hypertension – drug selection [ACD]

44. In 2006…
For those receiving monotherapy the most common agents
prescribed were blockers of the renin-angiotensin (RAS)
system.
Type of drug
Age < 55 yr, %
(SE)
Age > 55 yr or
Black, %
(SE)
Total % (SE)
Diuretics 12 (3.0) 26 (2.1) 23 (1.8)
Beta-blockers 33 (4.4) 18 (1.9) 21 (1.8)
RAS blockers 41 (4.6) 32 (2.3) 34 (2.0)
Calcium
antagonist
14 (3.2) 21 (2.0) 19 (1.7)
Other drugs
affecting BP
1 (0.9) 3 (0.8) 3 (0.7)
(Falaschetti et al., 2006)Type of Drugs Used, HSE 2006

45. Compelling and possible indications and contraindications for
major antihypertensive agents (BHS IV)
Class of drug Compelling indications Possible indications Caution Compelling
contraindications
Alpha-blockers Benign prostatic
hypertrophy
Postural hypotension,
heart failure
Urinary incontinence
ACE inhibitors Heart failure, LV
dysfunction, post MI or
established CHD, Type 1
diabetic nephropathy, 2o
stroke prevention
Chronic renal disease,
type II diabetic
nephropathy,
proteinuric renal
disease
Renal impairment,
PVD
Pregnancy,
renovascular
disease
ARBs ACE inhibitor intolerance,
Type II diabetic
nephropathy, hypertension
with LVH, heart failure in
ACE-intolerant patients,
post MI
LV dysfunction post MI,
intolerance of other
antihypertensive drugs,
proteinuric renal
disease, heart failure
Renal impairment,
PVD
Pregnancy,
renovascular
disease
Beta-blockers MI, angina Heart failure Heart failure, PVD,
diabetes (except with
CHD)
Asthma/COPD,
heart block
CCBs
(dihydopyridine)
Elderly, ISH Elderly, angina
CCBs (rate
limiting
Angina MI Combination with
beta-blockade
Heart block, heart
failure
Thiazide-thiazide-
like diuretics
Elderly, ISH, heart failure
2o
stroke prevention
Gout

46. If a fourth drug is required, one of the
following should be considered:
• A higher dose of a thiazide-type diuretic
or the addition of another diuretic (e.g.
low dose spironolactone)
• careful monitoring is recommended
• Beta-blockers or
• Selective alpha-blockers.
If blood pressure remains uncontrolled on
adequate doses of four drugs and expert
advice has not yet been obtained, this should
now be sought.
What next after ACD?

47. Refractory Hypertension
Drug selection?
• Low renin INCREASED THIAZIDE
LOOP DIURETIC
SPIRONOLACTONE
• Average renin ALPHA-BLOCKERALPHA-BLOCKER
• High renin BETA-BLOCKERBETA-BLOCKER
ALISKIRENALISKIREN

48. Thank you!
Visit http://www.simplyweight.co.uk for more information