Hyperlipidemia metabolic syndrome

Obesity Hyperlipidemia Fatty liver disease metabolic syndrome ( Insulin resistance syndrome / syndrome X)

BMI is Measure of obesity

BMI = weight in Kg/ (Height in meters ) ^2

Ideal BMI < 25

25-30 Overweight

> 30 obese

Obesity is a risk factor for

Fatty liver disease with steatosis, ( Nonalcoholic Steatohepatosis )

cardiovascular diseases (mainly heart disease, hypertension and stroke)

Type 2 diabetes

musculoskeletal disorders (especially osteoarthritis)

some cancers (including endometrial, breast, ovarian, prostate, liver, gallbladder, kidney, and colon)

Sleep apnoea syndrome

Chronic kidney disease

Correction of obesity

Behavior Therapy

uDiet

u limit energy intake from total fats and sugars;

uincrease consumption of fruit and vegetables, as well as legumes, whole grains and nuts

uengage in regular physical activity

u60 minutes a day for children and 150 minutes spread through the week for adults

Pharmacotherapy

uSibutramine – an appetite suppressant that works by blocking reuptake of serotonin and norepinephrine

uOrlistat - Pancreatic lipase inhibitor that blocks the absorption of up to one third of ingested fat. Metformin? ADHHD drugs?

Fatty Liver Disease

Hepatic Steatosis

Steatohepatitis

Fibrosis

Cirrhosis

Fatty Liver disease is

strongly associated with

overweight or obesity 80%

dyslipidemia 72%

type 2 diabetes mellitus 44%

shift work and travel that perturb normal feeding and sleep–wake cycles promote ( disrupt circadian rhythms )

the metabolic syndrome

Is the hepatic correlate of the metabolic syndrome

Course and prognosis

Nonalcoholic steatohepatitis is a dynamic condition

regress to isolated steatosis

smolder at a relatively constant level of activity

progressive fibrosis that leads to cirrhosis (F4 fibrosis)

Øno fibrosis [F0]

Øportal fibrosis without septa [F1]

Øportal fibrosis with few septa [F2]

Øbridging septa between central and portal veins [F3]

Øcirrhosis [F4])

Management

Manage as for metabolic syndrome

Adjunctive therapy

vitamin E

pioglitazone, an insulin-sensitizing agent with antiinflammatory actions, might also be considered.

Metabolic Syndrome

The deadly quartet

abdominal obesity

hyperglycemia

Dyslipidemia

hypertension

Criteria - presence of any 3 of the following

International DIabetes Federation (2006)

Increased waist circumference, with ethnic-specific waist circumference cut off-points ( table 2 )

PLUS any two of 2-6 in previous classification

Major risk factors 1

weight is a major risk factor for the

metabolic syndrome

u 5 percent of those at normal weight

u22 percent of those who are overweight

u60 percent of those who are obese

u10% of women and 15% of men with normal glucose tolerance

u42% and 64% of those with impaired fasting glucose

u80% with type 2 diabetes but the converse is not necessarily true

uage

urace

upostmenopausal status

usmoking

uphysical inactivity

upoor cardiorespiratory fitness

ulow household income

uhigh carbohydrate diet

usoft drink consumption

Clinical implications

The metabolic syndrome is an important risk factor for subsequent development of

Type 2 diabetes ( 10 fold Increase )

CVD( 2 fold ) Framingham study

Therapy

Treat underlying causes

overweight/obesity and physical inactivity

Treat cardiovascular risk factors if they persist despite lifestyle modification.

exercise

Treat insulin resistance with drugs that enhance insulin action

Metformin

Thiazolidinediones

Diet

Rich in

fruits, vegetables, nuts, whole grains, and olive oil

Low in

salt < 2.4g / day

carbohydrates and refined grains

Drug therapy

uIf diabetes or impaired glucose tolerance is present

Metformin 850 mg twice daily

uIn nondiabetics with metabolic syndrome

Intensive life style modification

Metformin / thaizolidionediones

Dyslipidaemia - Risk factors for CVD

a continuous, graded relationship between the serum total plasma cholesterol concentration and coronary risk

High concentrations of LDL are a particularly important risk factor for atherosclerosis

A low level of high density lipoprotein (HDL) is another important risk factor for atherosclerosis

Total cholesterol to HDL ratio —total cholesterol (or LDL-cholesterol) to HDL-cholesterol (HDL-C) ratio may have greater predictive value for CHD than serum total or LDL-cholesterol

Hypertriglyceridemia is associated with an increased risk for cardiovascular disease.

Lipoprotein(a) — Lipoprotein (a), also called Lp(a), is an independent risk factor for CHD.

Categorisation of dyslipidaemia?

Familial dyslipidaemia

Familial hypercholesterolemia —

high LDL-C level from birth,

tendon xanthomata,

early onset CHD in the absence of other CHD risk factors.

autosomal dominant disorder caused by defects in the gene

Management

Dietary Modification

Pharmacological

Statins (sim, atorva, rosu)

Fibrates

PSCK9 inhibitors

place for plaque stabilisation effect in high doses

muscle pain?

less than 3 times rise of transaminases (as long as that can continue use)

PCSK9 inhibitors

Disadvantages

ASCVD - atherosclerotic cardiovascular disease

Any form of IHD

Stable angina

Unstable angina

Infarction

Coronary artery stenosis > 50

CVD

Stroke

Stroke in evolution

TIA

Cerebral artery stenosis > 50%

Aortic aneurysm

Peripheral arterial disease

...

Primary Prevention of ASCVD

Treat to target

Non diabetics

uTotal Cholesterol < 200 mg%

uLDL < 100 mg%

Diabetics

uTotal Cholesterol < 170 mg%

uLDL < 70 mg %

Intensity of statin therapy

uLow intensity Statin Therapy

uDaily dose lowers LDL-C, on average, by <30%.

uModerate intensity Statin Therapy

uDaily dose lowers LDL-C, on average, by 30%. 50 %

uHigh intensity Statin Therapy

uDaily dose lowers LDL-C, on average, by >50%.

ASCVD risk calculator

http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate

EXTRA

Lipid lowering drugs

1 stattins 2 fibrates (ppar alpha) 3 PCSk9 inhibotrs 4. exetimibde 5 orlistat 6 cod oiver oil Surgeries for obesity.. Gastric bypass lipot No need to know histopathology classification of fatty disease Metabolos syndrome nothing to do with LDL Diet helps with diabetis and metabolic but in dislioidemia not much so important place for pharm Sim.. Atovva... Rosuvastatin Fenobdribates Glizofribrates Fibrates etc Muscle pain can withdraw statin. Statin induced nyopathy and renal failure Statin especially acute stage of MI high dosages Fibrates cn be used if only Tag high as more effect on this or as second choice Can use combination but more incidence of ttansmainase increase and nyopathy Other anti lipid drugs see pharmacology? Simvastatin low ... And atorvastatin middle and high in Sri Lanka doses........ Saliva dry and out and whether sleep dry throat Only way to increase HDL is by exercise... Statin might reduce HDL also But low HDL is an independent risk factor