Most medications have side-effects. I recommend intense exercise (aerobic, high frequency at moderate to vigorous if tolerated 6 days a week for one hour) coupled with frequent walking after meals. Dietary modifications include eating smaller meals spaced at about 5 to 6 times a day. Reduction of all baked goods. Fat from natural healthy sources high in MUFAs such as nuts (if tolerated). Reduction of saturated fat to 7% of daily calories. Increase in fiber from whole grains, vegetables and whole fruits.

Dear Joan,

While considering the effectiveness of new treatments, it is important to consider whether they improve patient outcomes, rather than focusing on biomarkers such as lipid levels.While finding a newer perspective you may think about Diet and drugs both.

Diet

• Plant stanols and sterols reduce LDL cholesterol levels and have other potentially beneficial effects, but their effect on CVD and atherosclerosis is unknown.

• A diet rich in fruit and vegetables is protective for CVD. The mechanism is uncertain, but it may be related to dietary inorganic nitrate, found particularly in leafy green vegetables.

• Specific foods that may be protective for CVD are lycopenes (a carotenoid found in tomatoes), polyphenols (found in red wine and tea) and pomegranate juice.

• Dietary patterns and markers of inflammation are linked, and this may be relevant to the development of atherosclerosis.

• Moderate alcohol intake may protect against coronary artery disease, by various mechanisms. However, when advising patients about alcohol consumption and heart health there are various factors to consider.

Drugs

• Nicotinic acid can effectively raise HDL cholesterol levels. Research on prolonged-acting nicotinic acid is ongoing.

• Fibrates reduce LDL cholesterol, reduce triglycerides and increase HDL cholesterol, and may improve CVD outcomes.

• The cholesterol-absorption inhibitor, ezetimibe, has a small effect in raising HDL cholesterol, which is potentiated by combining it with a statin or fibrate.

• Pharmacological inhibitors of the cholesteryl ester transfer protein (CETP) offer a potentially novel mechanism for raising HDL cholesterol levels.

Thank you, Anil. I think that raising HDL may be more effective in health outcome improvement than just lowering total cholesterol. The ratio of LDL to HDL is more important in determining health outcomes than just LDL or total cholesterol. In fact non-HDL cholesterol may be even more important in determining cardiovascular health than even the LDL-HDL ratio. I am attaching our publication concerning hypercholesterol measured by subtracting HDL from total cholesterol. This leaves all the atherogenic components of cholesterol such as apo-a, VLDL, etc.

In my opinion, we are in a transition phase in which statins  had shown its potential in the only way that has proven useful in increasing HDL (or effect) is to use recombinant apoAI (complex treatment , but has been successful), however, other ways of raising HDL (CETP inhibitors) were not beneficial results for total cardiovascular risk. Right now it seems to go beyond key recommendations for the general population and try to identify more precisely the metabolic disturbances transporting lipids (lipoproteins) and genetic associations involved.

For most moderate hyperlipidemia or those that are associated with a high risk to be associated with conditions with known comorbidity (DMII, renal failure, secondary prevention without major lipoprotein alterations etc), some of the therapeutic approaches or their associations (statins , fibrates, ezetimibe), along with other lifestyle measures may be sufficient. However, there are many situations where it is necessary to deepen in lipoprotein metabolism and seek more specific solutions. This journey has already begun and for those interested, I recommend the NEXT Review:

http://www.clinicaltherapeutics.com/article/S0149-2918(13)00347-0/pdf.

Thank you Drs. Joan, Anil and Juan

I agree with your comments, but to that patients that do not attain the recommend LDL-cholesterol target despite their use of high doses of statins and increased physical activity and strict diet control. What can we do more?

Paulo, as I said in my previous answer, I think there are two important things to do in these cases: first, to investigate the cause of elevated LDL, may be that the alteration does not adequately respond to conventional treatment (such as hiperLp (a), or isolated hypertriglyceridemia although in the latter case it is unlikely that the LDL is very high). IN the case of hyper Lp (a), for the moment, only nicotinic ac has shown some effect (although probably insuficientre for therapeutic purposes). However, there are other approaches, as F Kronenberg says in his article:

Genetic determination of lipoprotein (a) and Its association with cardiovascular disease: convenient does not always mean better (pages 243-247)

http://onlinelibrary.wiley.com/doi/10.1111/joim.12207/pdf

While most are still not available, and those are very specific approved indications (homozygous FH). The second issue is the ability to metabolize the drugs used (CYP and others), but little can be done in such cases.

The latter, in my opinion underutilized at the moment, is the LDL apheresis. Why not use it?

Dear All, quite interesting discussion! Lipoprotein Apheresis (LA) - the newest name of LDL-apheresis - is a great technique with some limitations not to be discussed here.

Its main indication is Homozygous Famiial Hyercholesterolaemia (FH). In my opinion LA will be coupled with lomitapide and only in some cases with PCSK9 inhibitors in the future.

The story is different if we deal with Heterozygous FH or subjects with Isolated or Combined forms of HyperLp(a)lipoproteinaemia. The aforementioned subjects in Europe are very often treated also by means of LA. The advent of PCSK9 inhibitors will probably result in a limitation of the use of LA in HeFH, including those intolerant or poor- or non responders to statins.

On the contrary, LA use in HyperLp(a)lipoprotaeinemic individuals, especially those with Coronary Artery Disease will furtherly increase as the drugs currently available are substantially useless in the treatment of the above mentioned severe genetically determined disorder and the so called novel drugs (all included) do not show any extraordinary impact on plasma Lp(a) levels. Thank you.

There is recent news on PCSK9 – A novel target to lower LDL. Look at the lecture by Ulf Landmesser in the highlights of the ESC congress in Barcelona. Look it up at ESC365. This class seems to add really a lot to existing strategies. 

With regard to HDL, we have to conclude that it is a marker rather than a maker of cardiovascular complications as strategies for elevating this fraction were not successful so far. 

Thierry,

Thank you for the insightful presentation. Removal of LDL seems promising when coupled with other strategies.

Hi Thierry: All the above answers are very useful, including change for better Style of Lyfe..Nowadays, there is a dicussion on LDL-Cholesterol as risk factor and the effect of statins  . As inflamatory marker I think that  high sensitivity C Reactive protein is a main biomarker  with easy laboratory  measurement. . But remember that secondary dyslipidemias are linked with numerous endocrine pathologies. The first intervention is  to find  the primary disease and its treatment.,including obesity, insulin resistance , metabolic syndrome, hypothiroidism,Diabetes Mellitus types 1 and 2, cystic ovary,anorexia nervosa with very high levels of LDL,,insulinoma, and many others. 

What mean "lowering cholesterol"? Reduction in absolute or percentage of cholesterol in certain lipoprotein fractions? variation of molar ratio between free or esterified cholesterol in respect to other components ? Structural variation of lipoproteins? their higher turnover ? reduction in Lp (a), or HDL2 or HDL3, in LDLsd, IDL, apo B100, VLDL? of all?

And, above all, in which patients and why? If we continue to simplify, is difficult to understand something. However, I agree with what is written by some colleagues just above, and in particular the Prof Stefanutti contextualises a specific and well-defined problem. I therefore propose to address the discussion on specific issues.