When Cholesterol becomes an Enemy

Cardiovascular disease is the leading cause of death universally and that includes India and other South Asian countries. A quarter of all the mortality is attributable to CVD.

Heart attacks and brain strokes are the predominant causes and are responsible for more than 80% of CVD deaths. The epidemic in India and neighbouring countries has an average more than the global average.

The other peculiarities are an earlier age of onset more malignant course and very high fatality. The preventive measures to contain this problem is multi factorial and needs targeted approach regarding health planning and reinforcements, early detection, life style measures and several innovative methods. 

One of the measures is the lipid lowering therapy using drugs and exercise in high-risk individuals.

Although cholesterol is a friend and not a foe as mentioned in one of my recent write ups but a sub fraction of it called the low-density lipoprotein cholesterol (LDLc) when oxidized becomes one of the important constituents of the fat build up in the arteries and this along with inflammation leads to rupture of the plaque and leads to clot formation by platelet deposition and overlying thrombus. This results in a heart attack.

The heart healthy levels of LDLc should be less than 100mgs/dl, levels between 100-159 are high risk for vascular events and levels more than 160 are considered dangerously high levels. 

Statin group of drugs also called HMG-CoA receptor inhibitors are the most studied and prescribed drugs for the prevention and treatment of cardio vascular disease (CVD).

Beginning in 1980s with lovastatin and in the recent years more potent agents like atorvastatin and rosuvastatin are used liberally in several classes of individuals.

Many scientists believe that the beneficial effects of statins are mainly because of their ant inflammatory propertiesbut reduction in the levels of LDLc is a very important marker.

A number of more agents like ezetimibe and bempedoic acid have also become available to supplement the effects of the statins. An injectable agent evolocumab (PCSK9 inhibitor) with a very potent capability of reducing LDLc has been in the market for several years now. It is indicated for extremely high-risk patients where other oral agents especially statins are not meeting the targets.  

In the recent past there have been several controversies associated with this class of drugs, confusing the patients as well as their treating physicians. This article will address these issues in particular.

Accepted indications for statin use:

1.  All patients with a history of a coronary event like myocardial infarction, unstable or stable angina, patients who have undergone an angioplasty with or without a stent or coronary artery bypass surgery.

2.  Patients with a history of a brain stroke or transient ischemic attack.

3.  Patients with disease of limb arteries leading to claudication or associated symptoms.

4.  Extremely high levels of LDLc (160 mgs/lit)

In these situations, statins in adequate doses lead to reduction of CV events by 25 to 40%. In general statins are well tolerated even in high doses. A study done by the author has shown that the highest dose of 80 mgs of atorvastatin is tolerated very well like the 40 mgs in Indian patients. 

Side effects of Statins

Most common side effects are myopathies, liver enzyme elevation and very rarely rhabdomyolysis. These side effects are usually resolved by reducing the dose or discontinuing the drug. For many years debate has been focussed on whether statins lead to cognitive decline, cancer and/or diabetes mellitus.

The recommendation of getting a periodic liver function test has been removed by most authorities including the US FDA. This is because serious liver injury with statins is very rare and unpredictable.

There has been a debate regarding the report of impaired memory, forgetfulness and confusion across all statins. Some of these reports are based on case reports and small unpowered studies.

Recent large meta- analysis and systematic reviews have however not shown any convincing evidence of cognitive disorders or cancer risk after statin therapy. However, a small increase in the incidence of Type 2 diabetes mellitus has been observed and confirmed. Given the overwhelming evidence of reduction in CV Events by 25-45% the small increase in diabetes mellitus is outweighed by the CV benefits seen in short and medium term for patients in whom statin therapy is recommended based upon the risk. Combining evidence from 13 studies show that treating 255 patients with statins for 4 years can lead to 1 additional case of diabetes mellitus, whereas 5.4 events of vascular disease are prevented. Thus, the risk of developing diabetes far outweighs the benefits.

What about Cataracts?

This is another reported side effect reported with no consistency in the literature. A recent large prospective study carried out on more than 13000 patients published in JAMA which included matched populations of statin users and non-users. The study confirmed that statin use does increase the occurrence of cataract more often than in nonusers. Weighing the risk benefit ratio should therefore be kept in mind when prescribing statins in patients with no underlying vascular disease for primary prophylaxis. 

Patients who do not benefit from Statins?

A number of trials with statins in high-risk patients have shown a marked reduction in recurrent events and mortality but a few have results to the contrary. Statin trials in elderly, patients with heart failure and patients with renal failure have not shown any mortality benefit. Indiscriminately prescribing statins in all patients with heart disease therefore is not the right decision. 


Cardiovascular diseases are the most common cause of mortality in our country. Combating them needs several measures of public health importance, right diet, exercise and use of drugs especially statins, which lower the LDLc significantly in high-risk individuals. These are in general very safe, well tolerated and efficacious in preventing vascular events like heart attacks and strokes. However, these always need to be prescribed by a physician. Everybody does not benefit from them. If used for appropriate indications their benefits overweigh the harms. 

The author is a Padmashiri and Dr B C Roy Awardee and Founder Director of Gauri Kaul Foundation.

Leave a Reply

Your email address will not be published. Required fields are marked *

14 + 12 =