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High Serum LDL/HDL Cholesterol Ratio an Emerging Risk Factor for Sudden Cardiac Death

Date : 09 Nov, 2018

Sudden Cardiac Death (SCD), generally defined as a sudden and unexpected death occurring within a short period of time after the onset of symptoms, accounts for 50% of all Cardiovascular Disease (CVD)-related deaths.

Low-density Lipoprotein cholesterol (LDL-c) plays a major role in the etiology of atherosclerosis. A broad body of evidence shows LDL-c as the primary atherogenic lipoprotein and High-density Lipoprotein cholesterol (HDL-c) as the predominant anti-atherosclerotic lipoprotein. It is established that Serum HDL-c is an independent protective risk factor for atherosclerotic CVD and Serum LDL-c as a causal risk factor for atherosclerotic CVD. Levels of these lipoproteins are now routinely measured in clinical practice for the screening of individuals with a high risk of CVD and being used as therapeutic targets for the primary and secondary prevention of CVD.

It has been suggested that an LDL-c/ HDL-c ratio is a better risk indicator for CVD than individual parameters.


Atherosclerosis, hardening of the arteries, is the leading cause of death worldwide. The disease triggers heart attack or stroke, with total annual deaths of 13 million worldwide.

Atherosclerosis is a disease in which a plaque builds up inside the arteries. The plaque contains Low density lipoprotein (LDL), macrophages, smooth muscle cells (SMCs), platelets, and debris. The plaque constricts the lumen of the blood vessel thereby increasing the shear force of blood flow. As the plaque continues to grow, the increased shear force may cause rupture of the plaque, possibly resulting in the formation of thrombus (blood clot) ischemic stroke and heart attack.

Cardiovascular Disease


In the population-based study of middle-aged men, it was observed that there is an increased risk of Sudden Cardiac Death (SCD) with a high LDL-c/ HDL-c ratio. Recent studies have shown that elevated HDL-c does not necessarily cause a decrease in the risk of CHD. In the Framingham study, 40% of CHD events occurred in individuals with normal or elevated HDL levels. Very high levels of HDL-c have also been demonstrated not to be associated with the risk of vascular events. Indeed, the evidence suggests that enhancing HDL-c function rather than increasing its levels, is associated with clinical benefit.

Based on data from clinical trials, a high LDL-c/ HDL-c ratio is associated with coronary plaque progression, whereas a decreased LDL-c/ HDL-c ratio achieved by pharmacological interventions may be associated with coronary plaque regression. Some studies have recommended that individuals with a high ratio of LDL-c/ HDL-c should commence treatment because of abnormal cholesterol levels. In addition, an elevated LDL-c/ HDL-c ratio has been suggested to be a predictor of coronary lipid-rich plaques and plaque vulnerability leading to an elevated SCD risk. 

In conclusion, a high LDL-c/ HDL-c ratio, but not the individual lipoprotein components, is associated with an increased risk of SCD. Further studies are needed to replicate these associations and assess the mechanistic pathways underlying the relationships.

Diagnostic Significance:

HDL Cholesterol:

High-density Lipoproteins (HDL) compose one of the major classes of plasma lipoproteins. They are synthesized in liver as complexes of apolipoprotein and phospholipid and are capable of picking up cholesterol and carrying it from arteries to the liver, where the cholesterol is converted to bile acids and excreted into the intestine.

An inverse relationship between HDL-cholesterol (HDL-C) levels in serum and the incidence/ prevalence of Coronary Heart Disease (CHD) has been demonstrated in a number of epidemiological studies. The importance of HDL-C as a risk factor for CHD is now recognized.

LDL Cholesterol:

Low Density Lipoproteins (LDL) are synthesized in the liver by the action of vari¬ous lipolytic enzymes on triglyceride-rich Very Low Density Lipoproteins (VLDLs). Specific LDL receptors exist to facilitate the elimination of LDL from plasma by liver parenchymal cells. It has been shown that most of the cholesterol stored in atherosclerotic plaques originates from LDL. For this reason the LDL Cholesterol concentration is considered to be the most important clinical predictor, of all single parameters, with respect to coronary atherosclerosis.

Accurate measurement of LDL Cholesterol is of vital importance in therapies which focus on lipid reduction to prevent atherosclerosis or reduce its progress and to avoid plaque rupture.

Methods in estimation of HDL Cholesterol and LDL Cholesterol:

  • Selective Detergent Method - Erba HDL and Erba LDL
  • Ultracentrifugation Method
  • Precipitation Method
  • Clearance Method
  • Homogeneous Method
  • Immuno Inhibition Method 
  • Direct Method
  • Friedewald Method
  • HPLC Method
  • Electrophoresis Method

Advantages of Erba Direct HDL and Direct LDL Kit:

  • Most Accurate
  • NIST (National Institute of Standards and Technology) Approved
  • WHO Approved
  • Selective Detergent Method
  • Highly stable, ready to use Liquid stable Reagents
  • No interference with high Triglycerides upto 2000 mg/dl, Bilirubin upto 40 mg/dl
  • Convenient Pack Sizes and can be tested in all types of Clinical Analyzers
  • High Linearity HDL Cholesterol-193 mg/dl and LDL Cholesterol – 263 mg/dl
  • Free Calibrator with the Kit
  • Easy to use

Erba Direct HDL and LDL Kit


  1. Straus SM, Bleumink GS, Dieleman JP, van der Lei J, Stricker BH, Sturkenboom MC: The incidence of sudden cardiac death in the general population. J Clin Epidemiol, 2004; 57: 98-102 
  2. Gillum RF: Geographic variation in sudden coronary death. Am Heart J, 1990; 119: 380-389 
  3. Steinberg D: The LDL modification hypothesis of atherogenesis: an update. J Lipid Res, 2009; 50Suppl: S376-
  4. Kannel WB, Wilson PW: Efficacy of lipid profiles in prediction of coronary disease. Am Heart J, 1992; 124: 768-774 
  5. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA2001;285:2486-2497.