SORTING OUT THE WHEAT FROM THE CHAFF

SORTING OUT THE WHEAT FROM THE CHAFF

Dr Tom MabinVergelegen Medi-Clinic

Somerset WestJULY 2004

Dr Tom MabinVergelegen Medi-Clinic

Somerset WestJULY 2004

Consequences of coronary plaque injury

Consequences of coronary plaque injury

CardiacIschemicEvents

Plaque Injury Thrombosis

ThrombusPlatelet

Atherosclerotic Plaque

The LDL-C–Lowering Efficacy of the Currently Available Statins

The LDL-C–Lowering Efficacy of the Currently Available Statins

DailyDose

AtorvaLipitor

Fluvalescol

Rosuvcresto

rPravaprava

Simvazocor

10 mg –39% - 46% –22% –30%

20 mg –43% –22% –48% –32% –38%

40 mg –50% –25% –58% –34% –41%

80 mg –60% –36% –71% –47%

Proven Mortality Benefits In Lowering LDL

Proven Mortality Benefits In Lowering LDL

A 28 % Reduction in LDL-C significantly reduces cardiovascular events

Major corronary events

Coronary deaths

Cardiovascular deaths

All-cause deaths

Per

cent

pro

port

ion

al ri

sk r

ed

uct

ion

Meta-analysis illustrating the beneficial effects of statin therapy

-31 %-29 %

-27 %

-21 %

•-35

•-30

•-25

•-20

•-15

•-10

•-5

•0

LaRosa et al, JAMA 1999; 282: 2340-2346

Cholesterol Management Cholesterol Management PharmacotherapyPharmacotherapy

*Daily dose of 40 mg of each drug, excluding rosuvastatin

TC = Total cholesterol, LDL-C = Low-density lipoprotein cholesterol, HDL-C = High-density lipoprotein cholesterol, TG = Triglycerides

Therapy TC LDL-C HDL-C TGPatient

tolerability

Statins* 19 – 37% 25 – 50% 4 – 12% 14 – 29% Good

Ezetrol 13% 18% 1% 9% Good

Nicotinic acid

(Niacin SR)

10 – 20% 10 – 20% 14 – 35% 30 – 70% Reasonable to poor

Fibrates 19% 4 – 8% 11 – 13% 30% Good

Yeshurun D et al. South Med J 1995;88:379–391. | NCEP. Circulation 1994;89:1333–1445. | Knopp RH. N Engl J Med 1999;341:498–511. | Gupta EK et al. Heart Dis 2002;4:399–409.

MIRACL: fatal or nonfatal strokeMIRACL: fatal or nonfatal stroke

0

0.5

1

1.5

2

0 4 8 12 16Time since randomization (weeks)

Cu

mu

lati

ve I

nci

den

ce (

%)

Relative risk = 0.50p=0.045

Atorvastatin

Placebo 1.6%

0.8%

Data on file, Pfizer Inc.

Statin Adverse EventsStatin Adverse Events• Side effects

- Headache – Myalgia – Fatigue

- GI intolerance – Flu-like symptoms

• Increase in liver enzymes Occurs in 0.5 to 2.5% of cases in dose-dependent manner Serious liver problems are exceedingly rare Manage by reducing statin dose or discontinue until levels return

to normal

• Myopathy Occurs in 0.2 to 0.4% of patients Rare cases of rhabdomyolysis Reduce by

• Cautiously using statins in patients with impaired renal function

• Using the lowest effective dose

• Avoiding drug interactions

• Careful monitoring of symptoms Presence of muscle toxicity may require the discontinuation of

the statin

• Side effects

- Headache – Myalgia – Fatigue

- GI intolerance – Flu-like symptoms

• Increase in liver enzymes Occurs in 0.5 to 2.5% of cases in dose-dependent manner Serious liver problems are exceedingly rare Manage by reducing statin dose or discontinue until levels return

to normal

• Myopathy Occurs in 0.2 to 0.4% of patients Rare cases of rhabdomyolysis Reduce by

• Cautiously using statins in patients with impaired renal function

• Using the lowest effective dose

• Avoiding drug interactions

• Careful monitoring of symptoms Presence of muscle toxicity may require the discontinuation of

the statin

• StatinsReduce angina

Reduce heart attacks

Reduce heart failre

Reduce stroke

Reduce peripheral vascular disease

Save more lives than any other drug family

• Very good safety profile

• Extremely cost effective

• StatinsReduce angina

Reduce heart attacks

Reduce heart failre

Reduce stroke

Reduce peripheral vascular disease

Save more lives than any other drug family

• Very good safety profile

• Extremely cost effective

Hazda

Hunter-GathererHumans

Wild Primates

Wild Animals

Inuit

Ikung

Pygmy

San

Baboon

Howler Monkey

Night monkey

Horse

Boar

Peccary

Black Rhinoceros

African Elephant

Modern Humans

1.3 1.8 2.3 2.8 3.4 3.9 4.4 4.9 5.4

Adult American

Mean Total Cholesterol (mmol/L)

AVERAGE IS

NOT

OPTIMAL

AVERAGE IS AVERAGE IS

NOT NOT

OPTIMALOPTIMAL

O’Keefe Jr. JACC 2004:43;2142-46

OPTIMISING LIPID PROFILES: DIET in all regimes

use STATINS if at all possible

OPTIMISING LIPID PROFILES: DIET in all regimes

use STATINS if at all possible • Aim for target levels: optimal

TC<4mmol/li LDL<2.0mmol/li• HDL >1.0mmol/li: exercise nicotinic acid alcohol• Not all generics are equal. check your blood results• Report possible side effects• Complimentaries that work

• Omega-3• Nicotinic acid

• Aim for target levels: optimal TC<4mmol/li LDL<2.0mmol/li• HDL >1.0mmol/li: exercise nicotinic acid alcohol• Not all generics are equal. check your blood results• Report possible side effects• Complimentaries that work

• Omega-3• Nicotinic acid

Global Mortality 2000: Impact of Hypertension and Other Health Risk Factors

Global Mortality 2000: Impact of Hypertension and Other Health Risk Factors

Attributable mortality in millions (total: 55,861,000)

Developing region

Developed region

0 87654321

High BP

Tobacco

High cholesterol

Unsafe sex

High BMI

Physical inactivity

Alcohol

Underweight

Ezzati et al. Lancet 2002;360:1347–60

Proportion of Patients Treated/Not Treated for Hypertension in Europe*Proportion of Patients Treated/Not

Treated for Hypertension in Europe*

Wolf-Maier et al. Hypertension 2004;43:10–17

75 74 74 73 68

0

20

40

60

80

100

Treated UntreatedPatients (%)

England Sweden Germany Spain Italy

*Age adjusted; patients aged 35–64 yearsHypertension = 140/90 mmHg threshold

JNC VII Lifestyle Modifications for JNC VII Lifestyle Modifications for Blood Pressure ControlBlood Pressure Control

Chobanian AV et al. JAMA 2003;289:2560–2572.

JNC VII=Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, BMI=Body mass index, SBP=Systolic blood pressure

Modification RecommendationApproximate SBP Reduction Range

Weight reduction Maintain normal body weight (BMI=18.5–24.9)

5–20 mmHg/10 kg weight lost

Adopt DASH eating plan

Diet rich in fruits, vegetables, low fat dairy

and reduced in fat

8–14 mmHg

Restrict sodium intake

<2.4 grams of sodium per day

2–8 mmHg

Physical activity Regular aerobic exercise for at least 30 minutes on most

days of the week

4–9 mmHg

Moderate alcohol consumption

<2 drinks/day for men and <1 drink/day for women

2–4 mmHg

From Elliott. J Clin Hypertens 2003;5(Suppl. 2):313Copyright © 2003, with permission from Blackwell Publishing

‘Controlling blood pressure with

medication is unquestionably one of the

most cost-effective methods of reducing

premature CV morbidity and mortality’

The South African Black populationThe South African Black population

1960’s <1% showed coronary atherosclerosis

1990’s >30% “

:

:

Baragwanath Hospital Experience

Autopsy Studies

1960

2000:

47% DIABETICS: average TC 5.2mmol/Li

:

:

2 per year

700 per year

Clinical Studies

Annual incidence of myocardial infarction

Overweight and Obesity Increase the Risk of Cardio-Overweight and Obesity Increase the Risk of Cardio-vascular Disease Mortality and All-Cause Mortalityvascular Disease Mortality and All-Cause Mortality

0.6

1.0

1.4

1.8

2.2

2.6

3.0

Rela

tive R

isk o

fC

ard

iovasc

ula

r D

isease

Mort

alit

y

BMI (kg/m2)>18

MenWomen

CVD Mortality

Data are from 1 million men and women followed for 16 years with an average age of 57 who never smoked and had no history of disease at enrollment.

Calle et al. N Engl J Med 1999;341:1097–1105.

25 30 >40

0.6

1.0

1.4

1.8

2.2

2.6

3.0

Rela

tive R

isk o

fA

ll-ca

use

Mort

alit

y

BMI (kg/m2)>18 25 30 >40

MenWomen

All-cause Mortality

Normal WeightNormal Weight OverweightOverweight ObeseObese

Normal WeightNormal Weight OverweightOverweight ObeseObese

“The Macdonald’s Equation”“The Macdonald’s Equation”

• Low energy expenditure +• Abundant cheap food

=

• +ve energy balance = OBESITY

• Low energy expenditure +• Abundant cheap food

=

• +ve energy balance = OBESITY

1 2 4

Fitness Level (Low to High)

3 50

10

20

30

40

50

60

70

Exercise Evidence: Effect on MortalityExercise Evidence: Effect on MortalityD

eath

Rate

(per

10,0

00) Men

Women

13, 344 healthy men and women followed for 8 years13, 344 healthy men and women followed for 8 years

Blain SN et al. JAMA 1989;262:2395–2401.

Low physical fitness is associated with increased mortalityLow physical fitness is associated with increased mortality

Benefits of fitness on mortalityBenefits of fitness on mortality

METS achieved %reduction in death

4.1-5.0 MET level achieved

5.1-6.0 38%

6.1-7.0 47%

7.1-8.0 47%

8.1-9.0 53%

>9.0 61%

>5000 males aged 65-92 years8 year follow up

1 MET =

“fitness” vs “fatness”

what is the “hazard ratio” of death from any cause over 20 years?

“fitness” vs “fatness”

what is the “hazard ratio” of death from any cause over 20 years?

Slim+fit HR 1.0

Obese+unfit HR 3.0

Slim+unfit HR 2.0

Obese+fit HR 2.0

Fitness is the common denominatorFitness is the common denominator

• Regular physical activity has CV health benefits at any weight

• The fitter you are the greater the benefit• The quickest incremental benefit is obtained

getting to a level of “moderate”fitness • = 150 min moderate intensity per week• =30mins daily 5 days/week

• Any aerobic exercise..hard walking;cycling;swimming;gym

• Regular physical activity has CV health benefits at any weight

• The fitter you are the greater the benefit• The quickest incremental benefit is obtained

getting to a level of “moderate”fitness • = 150 min moderate intensity per week• =30mins daily 5 days/week

• Any aerobic exercise..hard walking;cycling;swimming;gym

The “modern” disease equationThe “modern” disease equation

• Obesity+inactivity• Obesity+inactivity

hypertension

diabetes

cholesterol

Metabolic syndrome

WaistWaist

Waist?Waist?

Metabolic syndrome

BP

chol

diab

unfit