Keep re-inventing the Wheel

Statins and LDL – Cholesterol – Primary Prevention What’s fact in 2012

Many studies have over the past 20 years reported beneficial effects of statin administration in secondary cardiovascular disease prevention and the large Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis of individual data published in 2010 (170 000 individuals in 21 trials of statin regimens vs control and 5 trials comparing intensive vs less intensive regimens) has endorsed this view.¹ 

Indeed, lowering low-density lipoprotein (LDL) cholesterol by 1 mmol/L can reduce the incidence of major vascular events (myocardial infarction [MI], coronary death, stroke, or coronary revascularization) by approximately 20%. Despite these beneficial effects in secondary prevention, doubts exist as to the true role of statins in primary prevention. These agents can have important side effects and studies have not completely reassured clinicians of the overall net benefit of statins in low-risk subjects.^2,3

The CTT have now reported their findings⁴ regarding the role of statins in primary prevention, which will most certainly have important clinical implications.

The study – This new meta-analysis—funded by the British Heart Foundation, the UK Medical Research Council, Cancer Research UK, the European Community Biomed Programme, the Australian National Health and Medical Research Council, and the National Heart Foundation (Australia)—included individual participant data from 22 trials of statin vs control (n=134 537;median follow-up 4.8 years) and 5 trials of higher vs lower statin dosage (n=39 612; median follow-up 5.1 years).

End points were: major cardiovascular events, including nonfatal MI and coronary death), stroke, and coronary revascularization. Subjects in the study were subdivided into 5 categories: baseline 5-year major vascular event risk (no statin or low-intensity statin) <5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%. In each of these categories, the rate ratio (RR) per 1.0 mmol/L LDL-cholesterol reduction was assessed.

Main findings – Irrespective of age, gender, baseline LDL cholesterol, and previous vascular disease, LDL-cholesterol lowering with a statin was associated with a reduction in major vascular events (RR 0.79; 95% confidence interval [CI] 0.77-0.81; per every 1.0 mmol/L reduction). Of interest, the proportional reduction in events was at least as big in the two lowest risk categories as in the higher risk categories. In the lowest risk categories, statins reduced major events (RR 0.57; 99% CI 0.36-0.89; P=0.0012; and RR 0.61; 99% CI 0.50-0.74; P<0.0001) and number of coronary revascularizations (P<0.0001). In individuals without a history of cardiovascular disease, statins reduced both vascular mortality (RR 0.85; 95% CI 0.77-0.95) and all-cause mortality (RR 0.91; 95% CI 0.85-0.97). Regarding stroke, the reduction in risk in subjects with <10% 5-year risk of major events was similar to that in higher risk categories (P for trend=0.3). IMPORTANTLY reduction in LDL cholesterol with a statin did not increase the incidence of cancer, cancer mortality, or other non-vascular mortality.

 

Implications of these findings

This recent study supports the notion that statins may be more than useful in primary prevention. Of note, in individuals with a 5-year risk of major vascular events <10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in events of approximately 11 per 1000 over 5 years. This finding is important because 50% of all vascular events occur among individuals without previous vascular disease, who are considered to represent a low-risk category.⁵

Another relevant issue is that the benefits reported in the study exceed the known risks associated with statin therapy. These, however, should not be underestimated when consideration is given to the use of statins in low-risk patients. Statins are associated with dose-related increased risk of myopathy (0.5 per 1000 over 5 years) and rhabdomyolysis (incidence ≈0.1 per 1000 over 5 years).⁶ The risk of hemorrhagic stroke—particularly in the Asian population—was also higher in some previous studies,⁷ but the present meta-analysis showed an overall reduction in the risk of stroke. Sattar et al⁸ have suggested that statins might be associated with a proportional increase in the diagnosis of diabetes mellitus (~10%), but the incidence of diabetes observed in the primary prevention trials was 5% over 5 years (absolute excess 0.1% per year). Thus the beneficial effects reported in the recent CTT meta-analysis⁴ largely exceeded the potential harm of a slight increase in the incidence of diabetes.

As also discussed in the article,⁴ long-term follow-up statin trials have shown that the absolute reductions in major vascular events increase while the statin treatment is continued¹ and these benefits persist for at least 5 years after the treatment has stopped.

The Lancet meta-analysis⁴ contributes importantly to the current debate regarding whether statins are truly beneficial in primary prevention and its findings are likely to influence forthcoming international guidelines.

 

References
1. Cholesterol Treatment Trialists’ (CTT) Collaboration; Baigent C, Blackwell L, Emberson J, et al.Lancet. 2010;376:1670-1681.
2. Ray KK, Seshasai SR, Erqou S, et al. Arch Intern Med. 2010;170:1024-1031.
3. Redberg RF, Katz M, Grady D. Arch Intern Med. 2011;171:1594.
4. Cholesterol Treatment Trialists’ (CTT) Collaborators. Lancet. 2012 May 16. Epub ahead of print.doi:10.1016/S0140-6736(12)60367-5.
5. Kerr AJ, Broad J, Wells S, Riddell T, Jackson R. Heart. 2009;95:125-129.
6. Armitage J. Lancet. 2007;370:1781-1790.
7. Cheung BM, Lam KS. Lancet. 2010;376:1622-1624.
8. Sattar N, Preiss D, Murray HM, et al. Lancet. 2010;375:735-742.

Blessings Cardiologydoc

South African Omega-3 Index Experience 2012

To date only 312 South African’s have undergone the Omega-3 Index (test) to assess their red blood cell membrane for the fatty acid content.

Data from the Physician’s Health Study identified low Omega-3 level or high Omega-6: Omega-3 ratios as HIGH risk for subsequent cardiac events.  As the Omega-3 content increased in the cell membrane (increase in the Omega-3 Index) the risk for cardiac death fell dramatically. Healthy Omega-3 Index appears to be > 8% and is directly influenced by your diet.

South Africa has one of highest incidence of heart disease in the world.  Per 100 000 population death rates per year are approximately 700.  This is exactly the same death rate per 100 000 population due to HIV related deaths.

Obesity and overweight are of epidemic proportions in South Africa coupled with poor exercise and eating habits pretty much accounting for the high death rate from cardiovascular disease.

Up to 60% of the SA population are either obese or overweight with the demographics spread across all social classes.  In SA the high daily intake of energy dense calories from carbohydrate (60-70% of daily calories) and the high use of polyunsaturated vegetable oils (sunflower etc.)  together with a high intake of trans fat from “fast foods” is probably responsible for the “state-of-the-nation”.

The omega-3 (EPA and DHA) content; the omega-6 (AA): omega-6 to 3 ratio (omega-3 index) of the RBC membranes of South African’s tested pretty much summarizes the problem of our society with very poor levels of omega-3 and high levels of toxic omega-6 (Arachidinic Acid AA being the most common omega-6) recorded.

High levels of saturated fatty acids (SFA) with only 1% of individuals tested having favourable levels of SFA are an obvious concern and reflect POOR dietary practise.  Finally only 27% of people tested have low (<1.3%) trans fat confirming the really toxic heated oils used; the high intake of margarines and cookies cakes and biscuits all containing higher amounts of trans fat.

So how does the Cardiologydoc fare in the “state-of-affairs”. 

I eat an uncomplicated “low carbohydrate” (100 g/d) Eco-Atkins diet (2500 calories per day) with 55% calories from fat; 35% from protein and 10% calories from carbohydrate.  I eat high proportion of “whole food” fish with daily sardine/ pilchards as a snack and oily fish 3 times per week (salmon) as a main meal with stir fry and salad.  I take daily dairy (full cream yoghurt); moderate egg (10 per week) and small amounts of cheese and no more than 2 portions of 80 g mixed raw nuts and seeds (almonds; macadamia; sun flower seeds and pumpkin seeds) per day and occasional small amounts of biltong & dry wors.  I recently recorded the following Omega-3 Index:

I have started to collect my own database of Omega-3 index and can confidently state that the test absolutely reflects your dietary mix of fats. The good news is that you can influence your Omega-3 Index with attention to some simple ground rules:

1. Stick to “whole foods” rich in omega-3
2. Don’t use the omega-6 containing vegan oils (sunflower, peanut, corn, soya, cottonseed) – throw them away……
3. If you use oil; use cold pressed extra-virgin olive oil and try not to heat it (use non stick frying pans)
4. Use canola oil (better omega-3: 6) in moderation
5. Eat omega-3 enriched eggs
6. Keep raw nuts and seeds in moderation and use macadamia nuts for fat calories (avoid peanuts as a bean and cashews as high in carbohydrate)
7. Have a tin of sardine or pilchards on most days drained of oil as this is often cottonseed oil
8. Absolutely avoid all fried foods (in oil) and “fast foods” (deep-fried chicken etc)
9. Keep intake of green leafy vegetables and yellow, green, red pigmented vegetables high (natural anti oxidants)
10. Keep dairy in moderation depending on your diet type (full cream; fat-free; low-fat and low-carbohydrate)
11. Fruit intake according to your diet preference but low-glycaemic (citrus) and rich in pigments (berries) and stay off fruit juice (very high glycaemic-index)
12. Animal protein/fat and grass-fed organ meat in moderation probably no more that 1 to 2 x 200-250 g portions per week
13. Keep away from cakes; cookies; pies and pastry’s (tons of trans fat)

With a recent publication indicating the really POOR quality of “over-the-counter” Omega-3 supplements in South Africa I am tending to get more of my omega-3 intake for “whole foods”.

This study demonstrated in ~ 50 of the OTC preparations of Omega-3 in SA more than 50% of the preparations contained < 90% of the advertised EPA/ DHA content and >50% contained significant content of rancid oil.  The only GOOD news was the mecury content was very low…….

In summary:

The Omega-3 Index has a high correlation to your dietary discipline and is predictable for an individual (thanks to my dear wife for her permission to publish her result).

Currently we are NOT doing well in SA as only about 1 in 10 individuals reflect a healthy RBC membrane for fatty acid content which is key to cell stability and optimal cellular function. 

Blessings Cardiologydoc