Transcript Document

ESC guidlines-Cardiometabolic
risk
Doc.dr Amra Macić Džanković
Cardiovascular risk-score
• Multiple models are developed with aim to stratify cardiovascular
risk concerning of developing and worsening cardiovascular
diseases.
• European guidelines in 2000.years had determined using of
SCORE (Systematic Coronary Risc Evaluation) system. It was made
on statement of high prospective clinical trials.
• Concerning age,gender,smoking,systolic blood pressure,total
cholesterol/HDL,it had to proceed total risc of developing fatal
cardiovascular disease during next ten years
• The importance of this approach to the problem is in whitnessing
that apsolute risk of developing cardiovascular disease is
mutifactorial and that these factors are logarythmic complemented.
SCORE system
Multiplification of risk-factors
• Multiplification of risk-factors highly increase
chances for developing heart coronary
disease,stroke and diabetes mellitus type 2
• Appearance of multiple risk-factors is known
as METABOLIC SYNDROME and consists of:
central obesity,hypertension,high level of
triglyceride , low HDL and high level of fasting
plasma glucose
• It was reason for optimising this score,just
including these parametres and better term-
Cardiometabolic risk
Cardiovascular risk
Better term
CARDIOMETABOLIC RISK
W≥39mg/
dl
M ≥ 0.9
W ≥ 0.85
EGI
R
IR or
FI
>P75
ATPI
II
IDF Abd
obes
ity
BMI ≥ 30
k/m2
M ≥ 102
cm
W ≥ 88 cm
≥110
mg/dl*
40mg/dl
≥180
mg/dl
≥140/90
mmHg*
M ≥ 102
cm
W ≥ 88 cm
≥110
mg/dl*
M≥40mg/
dl
W≥50mg/
dl
≥150
mg/dl
≥135/85
mmHg*
M ≥ 94
cm
W ≥ 80
cm
≥100 M≥40m ≥150
mg/dl*
g/dl
mg/d
W≥50m
l*
g/dl*
≥135/85
mmHg*
Prevalence of metabolic syndrome
in hypertensives
• Figure 1.
• (Figures are percentages: ATP (figures in cursive) and IDF (figures
in bold))
•
Cardiometabolic risk
• Cardiometabolic risk is high prevalent in the
hypertensive population
• Needs to be incorporated to a correct stratification of risk
that has to be done in every hypertensive patient.
• Guidelines of the European Society of HypertensionEuropean Society of Cardiology consider the
concomitant finding of arterial hypertension and
metabolic syndrome as a situation of high-added
cardiovascular risk.
• The presence of cardiometabolic risk is accompanied by
a significant enhancement in the risk of developing
chronic kidney disease.
Diagnosis
• Finding of an enhanced waist circumference
(above 94 cm in males and 80 cm in females)
• accompanied by the above quoted alterations in
lipid profile :
• HDL-cholesterol below 40 mg/dl(1,0 mmol/l for
men and 1,2 mmol/l for women and
• serum triglycerides above 150 mg/dl(more than
1,7 mmol/l).
Metabolic syndrome
• Cardiometabolic risk is particularly prevalent in
patients diagnosed as having metabolic syndrome
• Elements to make the required correct diagnosis of a
metabolic syndrome, besides an increased waist
circumference, are:
• a low HDL-cholesterol and elevated triglycerides,
• the potential presence of blood pressure (BP) values
above 130/85 mmHg and
• a fasting serum glucose above 100 mg/dl (5,6
mmol/l)according to a recently revisited ATP-III definition
• Tend to excess procoagulants in coagulation status and
• High level of serum inflammatory factors .
Definition
• Cardiometabolic risk represents a situation
where the possibilities of developing
atherosclerotic cardiovascular disease and
diabetes mellitus are significantly enhanced as a
consequence of the presence of insulin
resistance and atherogenic dyslipidemia, this
latter characterised by the presence of low HDLcholesterol and high triglyceride levels .
Global cardiometabolic risk
•
Figure 2. Global cardiometabolic risk includes the presence of metabolic
syndrome and traditional cardiovascular risk factors.
Managment of patients with
cardiometabolic risk
-The aim of intervention is to achieve an optimal
reduction of risk.
-Lifestyle modifications counteract the effect of the
underlying risk factors (-abdominal obesity, physical inactivity and -atherogenic diet).
-Hypertensives also require a tight BP control, a
choice of antihypertensive treatment not
producing other metabolic disturbances, and
quite often, parallel drug treatment for
associated metabolic risk factors
Lifestyle interventions
•
•
•
•
Promotion of exercise and energy expenditure and the reduction of
overweight by caloric restriction (in the range of 500-1000 Kcal)with,
weight loss in 12 months and regular aerobic exercise of 30-45
minutes daily.
Lifestyle interventions have clearly beneficial effects on BP and the
lipid profile and reduce the incidence of new-onset diabetes .
Lowering salt intake and alcohol consumption have moderate BP
lowering effects, which are enhanced in conjunction with weight loss
and increased exercise
A diet rich in fruits, vegetables and low-fat dairy products (DASH
diet) substantially lowers BP.
the Mediterranean diet, which is also rich in fruits, vegetables, fish
and olive oil, has a favourable impact on atherogenic dyslipidemia in
metabolic syndrome patients (23).
BP control
• Metabolic syndrome is an indicator of high added
cardiovascular risk in hypertensives, thus indicating early
antihypertensive treatment to reach BP targets.
Diuretics increase the risk of new-onset diabetes
compared to placebo (23% increase for diuretics).
• Conversely, calcium channel blockers and, especially,
renin-angiotensin system blockers (angiotensin receptor
blockers and angiotensin-converting-enzyme inhibitors)
decrease this risk (33% decrease with ACE inhibitors
and 43% decrease with angiotensin receptor blockers).
• Antihypertensive treatment in hypertensives with high
cardiometabolic risk should focus on the inhibition of the
renin-angiotensin system with either ACE inhibition or
angiotensin blockade (25).
Antihypertensive drugs and new
onset of diabetes
study
incidence of new onset (%) diabetes in patients treated with
diuretics and beta-blockers
CAPPP
diuretics,beta-blockers
21 %
usp. captopril
CHARM
placebo ± SOC
22 %
usp. candesartan ± SOC
INVEST
atenolol ± HCTZ ili
trandolapril
15 %
usp. verapamil SR ± HCTZ ili
trandolapril
INSIGHT
co-amilozid ± β-blokator
30 %
usp. nifedipin GITS
LIFE
atenolol
25 %
usp. losartan
ALLHAT
klortalidon
21 %
43 %
usp. amlodipin
usp. lizinopril
HOPE
placebo ± SOC
34 %
usp. ramipril ± SOC
ASCOT
atenolol ±
bendroflumetiazid
30 %
usp. amlodipin ± perindopril
Hansson L, et al. Lancet 1999; 353: 611-6.
Pfeffer MA, et al. Lancet 2003; 362: 759-66.
Pepine CJ, et al. JAMA 2003; 290: 2805-16.
Brown MJ, et al. Lancet 2000; 356: 366-72.
Dählof B, et al. Lancet 2002; 359: 995-1003.
ALLHAT Collaborative Research Group. JAMA 2002; 288: 2981-97.
HOPE Investigators. N Engl J Med 2000; 342: 145-53.
Dählof B, et al. Lancet 2005; 366: 895-906.
Managment of non-hypertensive
patients with metabolic syndrome
• Non-hypertensive patients with metabolic
syndrome usually have high-normal BP (systolic
130-139 mmHg and/or diastolic 85-89 mmHg).
• sodium restriction or the adoption of the DASH
diet, in addition to caloric restriction and
increased exercise, could be helpful.
Management of hypertensive
patients with diabetes or chronic
kidney disease
• For patients that also have diabetes or chronic kidney
disease, antihypertensive therapy is mandatory .
• Inhibition of renin angiotensin aldosteron system is
renoprotective.Target for blood pressure control is
<130/80 mmHG.
• The diabetic patient usually requires a combination of
several anti-hypertensive drugs for satisfactory blood
pressure control.
• Screening for microalbuminuria and adequate blood
pressure-lowering therapy including the use of ACEi and
ARB improves micro- and macrovascular morbidity in
type 1 and 2 diabetes.
Managment of the remaining
subjects
•
In patients with high-normal blood pressure
Subjects with high-normal blood pressure were at an increased risk
of cardiovascular events compared to subjects with optimal blood
pressure (less than 120/80 mmHg).
• The rate of developing hypertension in a short period (3 years) for
those with BP higher than 120/80 mmHg has been reported as very
high (40% in subjects older than 64 with BP higher than 130/85
mmHg).
• Over a period of 4 years, stage 1 hypertension developed in nearly
two-thirds of patients with untreated prehypertension (values of 120139 and/or 80-89 mmHg), and that antihypertensive treatment
reduced the risk of incident hypertension in these patients.
Management of remaining patients
•
In patients with an increased LDL-cholesterol
Increased LDL-cholesterol is not considered a
component of metabolic syndrome, it must be always a
treatment priority.
• Statins at appropriate doses should be used in all
patients with diabetes or cardiovascular disease ,
irrespective of total or LDL-cholesterol levels.
• combination therapy with bile acid sequestrants or
ezetimibe may help to reduce the statin dose and seems
a reasonable alternative.
Managment of remaning patients
•
In patients with cardiometabolic risk but without diabetes or
cardiovascular disease
Treatment with 10 mg atorvastatin was effective in reducing
cardiovascular events when hypertension was accompanied by 3 or
more additional risk factors, including most that are contained in the
definition of metabolic syndrome .
The typical dyslipidemia in hypertensives with cardiometabolic risk is
characterised by low-HDL cholesterol and increased triglycerides.
current evidence recommends the use of fibrates or nicotinic acid in
hypertensive patients with metabolic syndrome and
hypertriglyceridemia
• these agents should used with caution in those receiving
concomitant statin treatment, especially at higher doses, due to the
increased risk of myopathy and liver disorders.
Managment of remaining patients
• In patients with impaired glucose
tolerance
• Treatment with metformin , acarbose and
thiazolidinediones decreases the risk of
new-onset diabetes in patients with
impaired glucose tolerance.
• A recent meta-analysis suggests a
deleterious effect of rosiglitazone on
cardiac outcomes.
Managment of weight loss
•
•
Sibutramine is the only drug affecting monoaminergic systems currently
approved for the long-term control of obesity (slightly increases blood
pressure and heart rate and should be used with caution) .
When sibutramine is coadministered with a combination of RAAS blockers
and calcium channel blockers, it does not interfere with the antihypertensive
effect of such combination.
•
Orlistat is an inhibitor of gastrointestinal lipases, especially pancreatic
lipase. It has a favourable influence on lipids and glycemic control,
especially in diabetics, although gastrointestinal tolerance is poor .
•
Rimonabant(Acomplia) is the first antagonist of the endocannabinoid
receptor CB1.
Rimonabant is a drug primarily directed to cardiovascular protection through
a direct reduction of the components of cardiometabolic risk.
•
Managment of the risk of
thrombosis
• Postprandial hyperglycemia, increased free fatty acids
and elevated triglyceride levels may all have adverse
effects on platelets, coagulation and fibrinolysis(high
level of PAI-1).
• Antiplatelet drugs such as low-dose aspirin or clopidogrel
represent an option in the management of hypertensives
with cardiometabolic risk.
• The benefit is probably higher in type 2 diabetics and
conclusive in those with previous CV disease.
• Efforts to control BP should be reinforced before the
introduction of aspirin.
Conclusion
• Simple clinical tools exist which identify subjects at a
higher risk of developing both type 2 diabetes and
cardiovascular disease, and thus having a high
cardiometabolic risk.
• The management of these subjects is based principally
on lifestyle measures, but various antihypertensive, lipidlowering, insulin sensitising, antiobesity and antiplatelet
drugs could be helpful in reducing cardiometabolic risk.
Population-based strategies are clearly necessary to
reduce the impact of underlying risk factors for
cardiometabolic risk (obesity, physical inactivity and
atherogenic diet).
• There is general agreement that more aggressive
therapy is required to further reduce the risk of new
diabetes and cardiovascular disease, even though
evidence is scarce.
Main problems of nowadays
modern life-style
1) We eat too
much

2) We walk too
short

3) We are always
in stress
®ZR
Further investigations
• Human genetic code and its importance
in stratifyng risk patients
??
• new peptides and other molecules with
their roles in atherotrombosis ??
• Stress and how to objective this ???*
• Working overtime is bad for the heart
New strategies
????