A large trial shows high levels of good cholesterol (HDL) are insignificant if bad cholesterol (LDL) is low

The more the high density lipoprotein (or HDL) cholesterol, or good cholesterol as it is generally called, the less the chances of a person suffering from a cardiovascular event. And the emphasis has always been on increasing HDL cholesterol and reducing the level of low density lipoprotein (LDL), which is also called the bad cholesterol.

Population-based studies have earlier shown that low HDL concentrations (<1.03 mmol/L) are a risk factor for cardiovascular disease. Thus increasing the level of HDL cholesterol reduces cardiovascular risk.

JUPITER trial results

But results of the JUPITER study published online on Thursday in The Lancet are contrary to the well recognised relationship between HDL and cardiovascular risk.

The JUPITER results show that levels of good cholesterol (HDL) in a person are of no consequence as far cardiovascular risk is concerned if LDL (bad cholesterol) has been substantially lowered. The LDL reduction is most often achieved with high-dose of statins.

JUPITER is a primary cardiovascular prevention trial that had enrolled 17,800 volunteers. It is a randomised double-blind trial.

In the case of the JUPITER trial, the 8,900 volunteers given 20 mg of statin drug, Rosuvastatin, per day showed reduced LDL cholesterol, and the HDL concentration had no bearing on cardiovascular risk.

The authors conclude that while HDL concentration is useful as part of cardiovascular risk assessment, its level cannot be used to predict the “residual vascular risk among patients… with very low concentrations of LDL cholesterol.”

The JUPITER trial found that the risk of a cardiovascular event in the dummy group (placebo) was lowered by as much as 46 per cent in those volunteers who had the highest concentration of HDL compared to those who had the lowest HDL levels.

The JUPITER trial found a 23 per cent reduction in cardiovascular risk for every 1.03 mmol/L (40 mg/dL) reduction of LDL. The reduction was achieved using statins.

Need for caution

The JUPITER trial results are contrary to other trial results. “Why HDL cholesterol concentrations did not predict cardiovascular risk at very low concentrations of LDL cholesterol is unclear,” notes the Comment published along with the JUPITER trial results.

The authors writing the Comment further note that when it comes to primary prevention of cardiovascular disease, the HDL cholesterol level may not predict cardiovascular risk if LDL cholesterol concentrations if less. Probably there is a need to look at other lipid measures to get a more accurate prediction of cardiovascular risk than HDL cholesterol when the LDL cholesterol levels are very low.

The Comment emphasises that further large trials are required to corroborate the JUPITER trial results.

Secondary prevention

The JUPITER trial looks at only primary prevention. Hence the correlation of HDL and LDL cholesterol and secondary cardiovascular disease can be established only when many large trials are undertaken.

Finally, it may be remembered that raising HDL cholesterol has been a major treatment strategy to reduce cardiovascular risk, especially in those who do not have a low LDL cholesterol concentration. Any change in this strategy should be made only when overwhelming evidence is available.

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