Fight Aging!

Statins work to reduce cardiovascular disease risk by reducing blood lipid levels. In the research here, the authors quantify the benefits that have been obtained through the use of this class of drug over the past few decades. This class of drug is broadly considered to be one of the more important contributions to the reduced rate of cardiovascular mortality over that span of time. The data here suggests that statins should be even more widely used than they are at present: there are incrementally greater gains that might be obtained.

The mechanism of cardiovascular damage influenced by statins is one in which lipids oxidized due to other mechanisms of aging drive the pace at which atherosclerosis progresses. Lowering overall lipid levels in the bloodstream also lowers the level of these problem damaged molecules, and so atherosclerosis is slowed. The logical step beyond this in order to produce much better classes of therapy, treatments capable of reversing this condition, is to remove the damaged lipids and their byproducts rather than just slow their impact. The SENS Research Foundation, for example, ran a program to uncover bacterial enzymes that might be modified to accomplish this task for 7-ketocholesterol. For now, however, the only available approaches involve improved ways to lower blood lipids, such as PCSK9 inhibitors. These should be better than statins, but still not as good as repairing the situation by specifically clearing damaged lipids.

Previous research has shown the benefit of statins for reducing high cholesterol and coronary heart disease risk amongst different patient populations. However, until now there has been no conclusive evidence from trials for current guidelines on statin usage for people with very high levels of low density lipoprotein (LDL) cholesterol (above 190mg/dL) and no established heart disease. After studying mortality over a 20-year period, researchers showed that 40mg daily of pravastatin, a relatively weak type of statin, reduced deaths from heart disease in participants by more than a quarter.

"For the first time, we show that statins reduce the risk of death in this specific group of people who appear largely healthy except for very high LDL levels. This legitimises current guidelines which recommend treating this population with statins." In addition, the findings challenge current approaches on treating younger patients with LDL elevations with a 'watch and wait' approach. Instead, even those with slightly elevated cholesterol are at higher long term risk of heart disease, and that the accumulation of modest LDL reductions over time will translate into large mortality benefits. "Our findings suggest that we should consider prescribing statins more readily for those with elevated cholesterol levels above 155 mg/dl and who also appear otherwise healthy."

This research follows on from a five-year 1995 study in which researchers observed the long-term effects of statins on patients involved in the West of Scotland Coronary Prevention Study (WOSCOPS) trial. The researchers took into account the original five-year study and followed the patients for a further 15 years. The WOSCOPS study provided the first conclusive evidence that treating high LDL in men with pravastatin for five years significantly reduces the risk of heart attack or death from heart disease compared with placebo. Statins were subsequently established as the standard treatment for primary prevention in people with elevated cholesterol levels.

Now, researchers have completed analyses of the 15-year follow up of 5,529 men, including 2,560 with LDL cholesterol above 190 mg/dL of the original 6,595, chosen because they had no evidence of heart disease at the beginning of the present study. Participants were aged 45-64 years. During the five-year initial trial they were given pravastatin or placebo. Once the trial ended the participants returned to their primary care physicians, and an additional 15-year period of follow-up ensued. The 5,529 men were split into two groups: those with 'elevated' LDL (between 155 and 190mg/dL) and those with 'very high' LDL (above 190mg/dL). The standard 'ideal' level of LDL for high risk patients is below 100mg/dL, but this varies depending on individual risk factors.

The researchers found that giving pravastatin to men with 'very high' LDL reduced twenty year mortality rates by 18 per cent. Statins also reduced the overall risk of death by coronary heart disease by 28 per cent, and reduced the risk of death by other cardiovascular disease by 25 per cent among those with very high LDL cholesterol. The 15-year follow up also meant the researchers could compare patients' original predicted risk of heart disease with actual observed risk. According to the risk equations for cardiovascular disease, 67 per cent of patients included in the WOSCOPS trial with LDL above 190mg/dL would have less than a 7.5 per cent risk of heart disease by year ten, and thus would not have been treated with statins based on that risk. However, the present study shows that in fact, this group actually had a 7.5 per cent risk by year five, meaning their ten year risk was 15 per cent. Following statin therapy, this group's ten year risk was reduced compared with those that were given placebo during the trial.

Link: http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_6-9-2017-18-48-55