Transcript Document

SORTING OUT THE WHEAT
FROM THE CHAFF
Dr Tom Mabin
Vergelegen Medi-Clinic
Somerset West
JULY 2004
Consequences of coronary plaque
injury
Platelet
Thrombus
Atherosclerotic
Plaque
Plaque Injury
Thrombosis
Cardiac
Ischemic
Events
The LDL-C–Lowering Efficacy of the
Currently Available Statins
Daily
Dose
Atorva
Lipitor
Fluva Rosuv Prava
lescol crestor prava
Simva
zocor
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
A 28 % Reduction in LDL-C significantly reduces cardiovascular events
Per cent proportional risk reduction
•0
Major corronary
events
Coronary
deaths
Cardiovascular All-cause deaths
deaths
•-5
•-10
•-15
-21 %
•-20
•-25
•-30
-29 %
-27 %
-31 %
•-35
Meta-analysis illustrating the beneficial effects of statin therapy
LaRosa et al, JAMA 1999; 282: 2340-2346
Cholesterol Management
Pharmacotherapy
TC
LDL-C
HDL-C
TG
Patient
tolerability
Statins*
19 – 37%
25 – 50%
4 – 12%
14 – 29%
Good
Ezetrol
 13%
 18%
 1%
 9%
Good
Nicotinic acid
10 – 20%
10 – 20%
14 – 35%
30 – 70%
19%
 4 – 8%
11 – 13%
 30%
Therapy
(Niacin SR)
Fibrates
Reasonable
to poor
Good
TC = Total cholesterol, LDL-C = Low-density lipoprotein cholesterol, HDL-C = Highdensity lipoprotein cholesterol, TG = Triglycerides
*Daily dose of 40 mg of each drug, excluding rosuvastatin
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 stroke
Cumulative Incidence (%)
2
1.5
1
0.5
Placebo
1.6%
Atorvastati
n
0.8%
Relative risk = 0.50
p=0.045
0
0
Data on file, Pfizer Inc.
4
8
12
Time since randomization (weeks)
16
Statin 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
• Statins
Reduce 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
Hunter-Gatherer
Humans
Hazda
Inuit
Ikung
Pygmy
San
Wild Primates
Baboon
AVERAGE IS
NOT
Howler Monkey
Night monkey
OPTIMAL
Wild Animals
Horse
Boar
Peccary
Black Rhinoceros
African Elephant
Modern Humans
Adult American
1.3
1.8
2.3
2.8
3.4
3.9
4.4
4.9
5.4
Mean Total Cholesterol (mmol/L)
O’Keefe Jr. JACC 2004:43;2142-46
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
Global Mortality 2000: Impact of
Hypertension and Other Health Risk Factors
Developing region
Developed region
0
1
2
3
4
5
6
7
8
Attributable mortality in millions (total: 55,861,000)
Ezzati et al. Lancet 2002;360:1347–60
Proportion of Patients Treated/Not
Treated for Hypertension in Europe*
Patients (%)
100
Treated
Untreated
75
74
74
73
68
England
Sweden
Germany
Spain
Italy
80
60
40
20
0
*Age adjusted; patients aged 35–64 years
Hypertension = 140/90 mmHg threshold
Wolf-Maier et al. Hypertension 2004;43:10–17
JNC VII Lifestyle Modifications for
Blood Pressure Control
Recommendation
Approximate 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
Modification
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
Chobanian AV et al. JAMA 2003;289:2560–2572.
‘Controlling blood pressure with
medication is unquestionably one of the
most cost-effective methods of reducing
premature CV morbidity and mortality’
From Elliott. J Clin Hypertens 2003;5(Suppl. 2):313
Copyright © 2003, with permission from Blackwell Publishing
The South African Black population
Baragwanath Hospital Experience
Autopsy Studies
1960’s <1%
:
showed coronary atherosclerosis
1990’s >30%
:
“
Clinical Studies
Annual incidence of myocardial infarction
1960 :2 per year
2000: 700
: per year
47% DIABETICS: average TC 5.2mmol/Li
Relative Risk of
All-cause Mortality
Relative Risk of
Cardiovascular
Disease Mortality
Overweight and Obesity Increase the Risk of Cardiovascular Disease Mortality and All-Cause Mortality
3.0
2.6
2.2
Men
Women
CVD Mortality
1.8
1.4
1.0
0.6
>18
3.0
2.6
2.2
Normal Weight
Overweight
25
BMI (kg/m2)
Men
Women
Obese
30
>40
All-cause Mortality
1.8
1.4
1.0
0.6
>18
Normal Weight
Overweight
25
BMI (kg/m2)
Obese
30
>40
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.
“The Macdonald’s Equation”
• Low energy expenditure
+
• Abundant cheap food
=
• +ve energy balance = OBESITY
Exercise Evidence: Effect on Mortality
Death Rate (per 10,000)
13, 344 healthy men and women followed for 8 years
70
Men
60
Women
50
40
30
20
10
0
1
2
3
4
Fitness Level (Low to High)
5
Low physical fitness is associated with increased mortality
Blain SN et al. JAMA 1989;262:2395–2401.
Benefits 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 years
8 year follow up
1 MET =
“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
• 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
Fitness is the common denominator
The “modern” disease equation
hypertension
• Obesity+inactivity
diabetes
cholesterol
Metabolic syndrome
Metabolic syndrome
unfit
BP
chol
Waist
Waist?
diab