Lipids and Cardiovascualr System
Management of lipid levels is as important as that of Daibetes Mellitus or
Hypertension or smoking. It is even more rewarding. Family Physicians in
Pakistan are not sensitized enough to this fact. There is no official CME
programme. Other than individual efforts there is only one way left. That is
through pharma industry. They concentrate on consultants and specialists.
Although it would be more rewarding for pharma industry if they start from
family physicians. They should be the first rather than last in the chain of
marketing.
How important is it to reduce lipid levels?
This year results of a study, conducted by American College of Cardiology have
been made public. This study included 30,000 patients who have suffered
AMI.Randomly half were given statins, irrespective of cholesterol levels,
without even measuring these. Results were remarkable. There was 33 % reduction
of reinfarction in those receiving statins. Overall improvement in all
parameters was significantly better than in those who were receiving placebo.
New, important, practice modifying, central theme of this interview.
Other than this study now there is overwhelming evidence that all heart patients
should have statins irrespective of their cholesterol levels. Patients with even
normal cholesterol levels do get enormous benefits from statins. All patients of
AMI should be given statins on day number one. Cholesterol levels are done only
to adjust the dose of statins. Statins have many other major benefits on
atheromas, in addition to lowering cholesterol levels.
Clustering of Pathologies. Underlying phenomenon in majority of undermentioned
is insulin resistance even with normal glucose levels
• Diabetes Mellitus
• Hypertension
• Ischaemic heart Disease
• Peripheral Vascular Diseases
• Stroke
• Hypercholesterolaemia & Hyperlipidaemias
All of these usually cluster in most of the patients. Various combinations are
present in any one single patient. In a study conducted by me in Mayo Hospital,
insulin resistance was present in 98 % of non-diabetic hypertensive patients.
Main Causes
• Genetic inheritance
• Environmental Factors exhibiting as
Obesity
Physical inactivity, lack of exercise.
Improper diet.
Obesity is usually apparent by increased waist/hip ratio.
Investigating hyperlipidaemias.
Lipid profile should be ordered instead of first getting cholesterol or
trigylcerides levels and later on again sending for HDL and LDL levels. For
treatment Trigylcerides, Cholesterol, HDL and LDL levels are required. These are
important lipids.
Indications for ordering Lipid Profile
• All individual above 40 yrs of age should be at least once screened.
• Diabetes Mellitus
• Hypertension
• Obesity
• Family history
Blood sample for Lipid profile should be taken after 14 hours of fasting. For
monitoring of treatment this should be repeated after 3 months.
HDL /LDL ratio is useful. It further differentiates types of cholesterol and
lipids.
High Density Lipids (HDL) & Low-Density Lipids (LDL) lipoprotiens. These two, in
a simplifying statement, we can say are transporters of cholesterol from the
blood vessels to the liver and in the reverse direction.
HDL collects cholesterol from blood vessel walls (Thus atheromas) and transports
it to liver for further disposal. So it is a beneficial lipid. There is no
specific drug, at the moment, to increase its levels but many are in developing
stage.
LDL acts in opposite direction. It transports cholesterol from liver to blood
vessels. So it is a harmful lipid. Exercise, specific diet and many drugs are
there to lower it. Stress raises its levels. That is why after AMI it is raised
and remains so for many weeks. There is further subclassification of LDLs.One
variety SP LDL is 10 times more oxidant than other LDLs and so much more
dangerous.
Normal Levels.
There is no hard and fast rule. Usually reported normal values serve only as a
reference levels in those individuals who neither have any manifest disease nor
any risk factor for above-mentioned diseases. Rather than normal values one
should talk of target values in those patients who have relevant diseases or who
have risk factors such as obesity, or smoking or family history.
Risk stratification should bring down values from so called normals. Cholesterol
values lower than 100 mgs/dl and Triglycerides levels lower than 125 mgs/dl may
be the targets.
Primary prevention of events like infarction or stroke may have higher target
values than in the patients who are already suffering from a relevant disease.
Here for secondary prevention criteria have to be very stringent and values
lower than in primary prevention.
Pathological Types of Hyperlipidaemias
Without going in much details we can say following three types of abnormalities
are seen commonly.
• Hypercholesterolaemia: Where only cholesterol levels are increased.
• Hypertriglyceridaemia: When only triglycerides are increased
• Mixed: Both are raised.
Management of each type is different.
Isolated Hypertriglyceridaemias
Usually these are familial. These also occur under following conditions.
• Diabetes Mellitus
• Hypothyroidism
• Nephrotic syndrome
• Liver diseases.Obstructive Jaundice
• Stressful conditions.
• After rich fatty meals.
In addition to diet control, weight loss & exercise combined therapy of statins
and fibrates is useful.
Atheroma formation and its rupture
Target organ is blood vessel. Many factors can damage the endothelium of blood
vessels. Few have been defined and majority is still unrecognized. Oxidized
Oxygen radicals are one of these. Endothelium is the largest endocrine organ of
the body. It is a very active tissue. If total endothelium of body is spread on
ground it can cover 8 tennis courts. It secretes more than 1000 peptides
including good and bad ones. Once it is damaged, blood enters subendothelial
space. Growth promoting factors are released. Connective tissure is laid down.
Endothelium starts proliferating. Slowly and slowly a plaque starts appearing in
the vessel lumen. Surface is covered by fibrous cap and lumen consists of a
meshworkd of platelets, RBCs and lipids. Plaque keeps on increasing till it
obstructs vessel lumen upto 40 –50 %. But circulation remains intact. A point
comes when this atheroma ruptures and bursts in the lumen. This endpoint causes
maximum damage. It produces local obstruction and at the same time thrombi are
embolized.
Measures to lower lipids (Cholesterol & Triglyceride) levels.
1 Diet 2 Exercise 3 Weight Loss
All three reduce cholesterol levels upto 10 % of the original figures. Before we
consider drugs, which modify lipid levels, it is better to consider what happens
in the atheroma formation.
Advantages of Statins.
• Cholesterol lowering effect
• Stablizing of fibrous cap of atheromas so preventing rupture of these. This
action is through collegenase enzymes. ACE inhibitors also demonstrate this
effect.
• Anti-inflammatory effect on subendothelial (subatheromatous) inflammation.
Xanthelasmas These fat deposits should be taken only as markers for ordering
lipid profile. Usually these are present in familial hyperlipidaemias,
obstructive jaundice or nephrotic syndrome. Very difficult to treat. Only
genetic therapy promises some hope. Statins are of little help.