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

Principal

criteria

Abdominal obesity

Glucose HDL Triglyc

BP

WHO

DM, GI or IR

BMI ≥ 30 k/m2

M ≥ 0.9

W ≥ 0.85

M≥35mg/dl

W≥39mg/dl

≥150 mg/dl

≥140/90 mmHg*

EGIR

IR or FI

>P75

BMI ≥ 30 k/m2

M ≥ 102 cm

W ≥ 88 cm

≥110 mg/dl*

40mg/dl ≥180 mg/dl

≥140/90 mmHg*

ATPIII

M ≥ 102 cm

W ≥ 88 cm

≥110 mg/dl*

M≥40mg/dl

W≥50mg/dl

≥150 mg/dl

≥135/85 mmHg*

IDF Abd

obesity

M ≥ 94 cm

W ≥ 80 cm

≥100 mg/dl*

M≥40mg/dl

W≥50mg/dl*

≥150 mg/d

l*

≥135/85 mmHg*

AHA

M ≥ 94 cm

W ≥ 80 cm

≥100 mg/dl*

M≥40mg/dl

W≥50mg/dl*

≥150 mg/d

l*

≥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 Hypertension- European 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 HDL-cholesterol 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

Hansson L, Hansson L, et alet al. . LancetLancet 1999; 1999; 353353: 611-6.: 611-6.Pfeffer MA, Pfeffer MA, et alet al. . LancetLancet 2003; 2003; 362362: 759-66.: 759-66.Pepine CJ, Pepine CJ, et alet al. . JAMAJAMA 2003; 2003; 290290: 2805-16.: 2805-16.Brown MJ, Brown MJ, et alet al. . LancetLancet 2000; 2000; 356356: 366-72.: 366-72.

ASCOTASCOT aatenolol ± tenolol ± 3030 %% uspusp.. amlodipin ± perindopril amlodipin ± perindopril bendroflumetiazidbendroflumetiazid

studystudyincidence of new onsetincidence of new onset ((%%) diabetes in patients treated with ) diabetes in patients treated with diuretics and beta-blockersdiuretics and beta-blockers

CAPPPCAPPP diuretics,beta-blockersdiuretics,beta-blockers 2121 % % usp.usp. ccaptoprilaptopril

CHARMCHARM pplacebo ± SOC lacebo ± SOC 2222 %% usp.usp. ccandesartan ± SOCandesartan ± SOC

INVESTINVEST aatenolol ± HCTZ tenolol ± HCTZ iliili 1515 %% usp.usp. verapamil SR ± HCTZ verapamil SR ± HCTZ iliilitrandolapriltrandolapril trandolapril trandolapril

INSIGHTINSIGHT cco-amilozid ± β-bloo-amilozid ± β-blokatorkator 3030 %% usp.usp. nifedipin GITSnifedipin GITS

LIFELIFE aatenololtenolol 2525 %% usp.usp. losartanlosartan

ALLHATALLHAT kklortalidon lortalidon 2121 % % uspusp.. amlodipin amlodipin4343 % % uspusp.. li lizzinoprilinopril

HOPEHOPE pplacebo ± SOC lacebo ± SOC 3434 % % uspusp.. ramipril ± SOCramipril ± SOC

Dählof B, Dählof B, et alet al. . LancetLancet 2002; 2002; 359359: 995-1003.: 995-1003.ALLHAT Collaborative Research Group. ALLHAT Collaborative Research Group. JAMAJAMA 2002; 2002; 288288: 2981-97.: 2981-97.HOPE Investigators. HOPE Investigators. N Engl J MedN Engl J Med 2000; 2000; 342342: 145-53.: 145-53.Dählof B, Dählof B, et al. Lancetet al. Lancet 2005; 2005; 366366: 895-906.: 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 120-139 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, lipid-lowering, 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 Main problems of nowadays modern life-stylemodern 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 ????