The same old diet recommendations in New Zealand’s new cardiovascular disease prevention guidelines

Screenshot 2018-06-05 09.47.56.pngCardiovascular Disease Risk Assessment and Management for Primary Care.
https://www.health.govt.nz/system/files/documents/publications/cvd-risk-assessment-and-management-for-primary-care-v2.pdf

Its the same stuff – saturated fat is bad for you. Avoid it, and replace it with polyunsaturated and monounsaturated fats

But hang on minute, is this still the best advice you have?  And will it really prevent people getting cardiovascular disease?

The advice to limit saturated fat misses more important effects?

We think there are a few holes in the argument. Or at least we aren’t getting the full story.

They say……

“Substituting dietary saturated fat with mono and polyunsaturated fats is the most effective dietary approach to reducing low-density lipoprotein cholesterol (LDL-C) while maintaining or increasing high-density lipoprotein cholesterol (HDL-C).”

But we think this misses the mark – polyunsaturated and mono-unsaturated fats lower LDL because of their effect on the LDL-receptor and on ApoB catabolism. But they only raise HDL when substituted for carbohydrate, because they are fats, and fats in general stimulate the release of ApoA1, the seed of HDL, from gut and liver cells.

A high intake of linoleic acid lowered LDL and raised HDL when it was added to the baseline fat intake (e.g. replaced carbohydrate in the diet), but lowered both LDL and HDL when it replaced saturated fat.[1]

This might seem to be picking on the details, but we think it is important. As it stands above replacing saturated fats isn’t the most effective way of changing the fats in your diet to improve your chances of avoiding clogged arteries.

We think better advice might to be to replace the carbs your eat with fats from minimally processed foods.

The classic feeding study meta-analysis of Mensink et al. makes clear the benefits of replacing carbohydrate with various fats. This is worth quoting at length.[2]

The cis MUFAs had a modest but significant LDL cholesterol–lowering effect relative to carbohydrates. All 3 classes of fatty acids increased HDL cholesterol relative to carbohydrates. Unsaturated fatty acids increased HDL cholesterol less than did SFAs. As a result, the replacement of 1% of energy in the form of SFAs with an equal percentage in the form of cis MUFAs is predicted to lower HDL-cholesterol concentrations by 0.002 mmol/L. A similar decrease is expected when 1% of energy in the form of MUFAs is replaced with an equal percentage in the form of PUFAs. These effects, however, are small compared with those of replacement of carbohydrates with any of the 3 classes of fatty acids. Replacement of carbohydrates with any class of fatty acids decreased fasting serum TG concentrations (Table 1). The effect was slightly but not significantly larger for PUFAs than for other fatty acids. This contrasts with the powerful TG-lowering effect of n−3 PUFAs from fish, which is evidently not shared by linoleic acid, the major n−6 PUFA. Replacement of carbohydrates with SFAs did not change apo B concentrations. The cis unsaturated fatty acids, however, decreased apo B, and this effect was slightly stronger for PUFAs. SFAs and MUFAs increased apo A-I concentrations relative to carbohydrates. PUFAs did not significantly change apo A-I concentrations.

In other words, all benefits expected in terms of increasing unsaturated fats are seen when fat replaces carbohydrate, and this has the additional benefit of decreasing triglycerides – it’s better for the TG/HDL ratio. We explained how this effect plays out in terms of ApoB and ApoA1, even if saturated fat increases, in an earlier blog.

The substitution meta-analysis of Farvid et al makes it clear that a similar effect – an association with risk here, not just risk markers – is even seen in prospective cohort studies, confounded though those are.[3]

“9 cohort studies evaluated substitution of LA for carbohydrate showed that substituting 5% energy intake from LA for carbohydrates lowered risk with about 10%. A slightly lower risk benefit was seen for substitution of LA for SFA.”

So if it’s better, or at least not worse, to replace carbs with unsaturated fats and leave saturated fats as they were, why isn’t this offered as advice?

The most at risk benefit the least from current advice

The problem with the existing advice is is, that even the expected effects of replacing SFA with unsaturated fats are unlikely to be seen if you are overweight or insulin resistant. The studies being relied on for guidelines are based, overall, on healthy volunteers – unfortunately for people depending on these results, insulin sensitive people are at very low risk of CVD, and LDL has little correlation with their risk, but the opposite is true for the insulin-resistant.[4]

Design: A randomized, double-blind, 3-period crossover controlled feeding design was used to examine the effects on plasma lipids of 3 diets that differed in total fat: the AAD [designed to contain 38% fat and 14% saturated fatty acids (SFAs)], the Step I diet (30% fat with 9% SFAs), and the Step II diet (25% fat with 6% SFAs). The diets were fed for 6 wk each to 86 free-living, healthy men aged 22–64 y at levels designed to maintain weight.
Results: Compared with the AAD, the Step I and Step II diets lowered LDL cholesterol by 6.8% and 11.7%, lowered HDL cholesterol by 7.5% and 11.2%, and raised triacylglycerols by 14.3% and 16.2%, respectively. The Step II diet response showed significant positive correlations between changes in both LDL cholesterol and the ratio of total to HDL cholesterol and baseline percentage body fat, body mass index, and insulin. These associations were largely due to smaller reductions in LDL cholesterol with increasing percentage body fat, body mass index, or insulin concentrations. Subdivision of the study population showed that the participants in the upper one-half of fasting insulin concentrations averaged only 57% of the reduction in LDL cholesterol with the Step II diet of the participants in the lower half.

Whereas the drops in HDL and rise in TG (from the stepwise reductions in fat and replacement with carbs) probably cancelled out any benefit from lower LDL in responders here, the most IR subjects weren’t even getting the benefit of lower LDL! That’s where a low carb approach to lipid management would have come in handy –  if insulin and body fat % became lower, these subjects would experience a greater response to any PUFAs and MUFAs in their diet.

What is LDL anyway?

The LDL-cholesterol (LDL-C) in a standard lipid panel is just a calculated proxy for ApoB. On a low carb diet, with low TGs, you’ll start to get discordance between LDL-C and ApoB. That is, sometimes the LDL-C count can go up even when there’s a reduction in ApoB; this is because the ApoB particles become larger and less atherogenic. We see this in the Virta Health type 2 diabetes study – there’s a 9% rise in LDL cholesterol but ApoB has decreased non-significantly, LDL-P (the actual number of LDL particles) has decreased,  small LDL-P (the actual number of the most atherogenic type of LDL particle) has decreased massively, and of course everything else has improved.[5]

Virta Fig 1

Curiously, triglycerides are only mentioned in the new guidelines as a risk factor for pancreatitis, which is one pathway to diabetes, and not as a CVD risk factor (and the cut off here is 11 mmol/L. Wow). We’re not sure why this is. Has the new shift to non-fasting tests made it impossible to use the old risk calculations, which clearly defined risk in terms of LDL, TG, and HDL? Is there an assumption that because everyone in NZ should be eating a high carb diet, there is no point giving advice to lower TGs? It’s a mystery. TGs (with more reasonable cut-offs) are still a risk factor for people with LDL controlled by statins.[6]

Triglycerides are important

Here’s a rare, good quality study (n= 3590) from the Framingham Offspring Cohort that actually looked at risk based on all 3 lipid measures, in a population not taking any lipid-lowering drugs. The high/low cut of for HDL was 40 mg/dL for men and 50 mg/dL for women, which some labs will tell you is still too low (we can do better !). The lowest TG cut-off of 100 mg/dL is also a bit high (again, we can do better !) – the 2 cut-offs combined give a TG/HDL ratio of 2.5 for men and 2 for women, whereas the insulin-sensitive groupings in other studies tend to have a mean TG/HDL ratio of ~1.1 (consistent with LDL particle size in people with type 2 diabetes improving below a TG/HDL ratio of 1.5).
Even so, you can see that if HDL is high and TG low, risk is low, and any difference in the LDL level has little effect. Note that this population wasn’t screened for familial hypercholesterolaemia genes, which would have impacted risk across all higher LDL categories.[7]

Framingham

Statins – good for some?

When statins (okay we will wade into this just a little) are prescribed in secondary prevention (i.e. after a heart attack), they are very effective in preventing a second event in the most insulin-resistant people, calculated by the TG/HDL ratio. The NNT (number needed to treat) over 6 years in the IR group in the 4S study was 6, which is amazingly good – but statins didn’t really make much difference to the most insulin-sensitive, who are at an almost equally low risk if taking a placebo – their NNT in 4S was 36.[8]
Remember, these insulin sensitive cases, who don’t seem to benefit much from LDL lowering, are also the ones likely to see the biggest LDL drop if they replace saturated fats with unsaturated fats (it’s the opposite with statins, so the insulin-sensitive people below were actually on a higher statin dose to get the same LDL reduction – so much for extrapolating between diet and drug effects).

4S Fig 1 Event Free Survival
4S – Open squares are highest TG/ lowest HDL quartile on statin, closed squares on placebo. Open circles are lowest TG/ highest HDL quartile on statin, closed circles on placebo.

Age increases risk?

It’s also worth questioning the use of age as a continuous variable in risk calculations. Of course your risk of dying from any disease goes up as you age, but trials of statins in elderly populations for primary prevention are few, and include 1) the ALLHAT open-label trial where statin use was not beneficial in a post-hoc analysis of the elderly patients (n=2867): this was a rare trial not funded by industry and came closest to a real-world model of prescribing.

The hazard ratios for all-cause mortality in the pravastatin group vs the UC group were 1.18 (95% CI, 0.97-1.42; P = .09) for all adults 65 years and older, 1.08 (95% CI, 0.85-1.37; P = .55) for adults aged 65 to 74 years, and 1.34 (95% CI, 0.98-1.84; P = .07) for adults 75 years and older. Coronary heart disease event rates were not significantly different among the groups.[9]

2) The PROSPER RCT (n=5804) in which CHD was reduced, but all-cause mortality was not affected (0·97 (0·83–1·14)) due to increases in other causes of death.[10]

3) The JUPITER and HOPE3 trials, in which a recent post-hoc sub-group meta-analysis has revealed benefit for the elderly patients. (JUPITER was a statin trial targeted at patients with low LDL but high CRP, i.e. inflammation, and had most clear evidence of benefit in cases with low HDL at baseline, which again is evidence of statins being far more effective in the insulin-resistant). The older people were, the more likely they were to stop taking statins, but we can’t say how much of this is due to increasing side effects with age, because side effects were poorly recorded in these early statin trials.[11]

Risk management in the elderly may also be complicated by the fact that total cholesterol and LDL are often protective risk markers in older populations. For example, in the Danish registry of people without pre-existing heart disease or diabetes higher LDL is associated with lower mortality, compared with LDL under 2.5 mmol/L, in those over 50. That this included those with very high LDL – above 4 mmol/L – rules out reverse causality. Though statin use (by about 1 person in 4) was also associated with lower mortality in this population, there was no interaction between statin and cholesterol (i.e. statins didn’t explain the LDL difference either way). HDL between 1-2 mmol/L was protective compared with HDL <1 mmol/L (39 mg/dL); HDL ≥ 2 mmol/L was protective in women but not men (very high HDL levels can reflect heavy drinking), and higher TG was associated with increased mortality. In other words, the TG/HDL ratio – which correlates with fasting insulin, the 2-hour insulin response to glucose, and measures of insulin resistance – still predicted the risk of dying even in a population where LDL was pointing the other way.[12]

 

Better diet prescription?

If we’re going to prevent diabetes and cardiovascular disease, it’s obvious we need to identify insulin resistance and prescribe diets accordingly. Prescribing diets that seem to lower LDL based on studies in healthy, insulin-sensitive people isn’t going to achieve much for the insulin-resistant who are most at risk, especially if these are still high carb, fat-phobic diets. At the very least, people at risk should be told to cut out sugar and refined starches, the products driving their insulin and triglycerides.

Whichever way you look at it – whether you think low carb is best, or you just favour a real food or Mediterranean diet with less sugar and processed food – the diet advice given in these guidelines, and supposed to be passed on by every GP in the country, represents a wasted opportunity.


References

[1] Rassias G, Kestin M, Nestel PJ. Linoleic acid lowers LDL cholesterol without a proportionate displacement of saturated fatty acid. Eur J Clin Nutr. 1991 Jun;45(6):315-20.

[2] Ronald P Mensink, Peter L Zock, Arnold DM Kester, Martijn B Katan; Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials, The American Journal of Clinical Nutrition, Volume 77, Issue 5, 1 May 2003, Pages 1146–1155, https://doi.org/10.1093/ajcn/77.5.1146

[3] Farvid MS, Ding M, Pan A, et al. Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies. Circulation. 2014;130(18):1568-1578. doi:10.1161/CIRCULATIONAHA.114.010236.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334131/

[4] Michael Lefevre, Catherine M Champagne, Richard T Tulley, Jennifer C Rood, Marlene M Most; Individual variability in cardiovascular disease risk factor responses to low-fat and low-saturated-fat diets in men: body mass index, adiposity, and insulin resistance predict changes in LDL cholesterol, The American Journal of Clinical Nutrition, Volume 82, Issue 5, 1 November 2005, Pages 957–963, https://doi.org/10.1093/ajcn/82.5.957

[5] Nasir H. Bhanpuri, Sarah J. Hallberg, Paul T. Williams, Amy L. McKenzie, Kevin D. Ballard, Wayne W. Campbell, James P. McCarter, Stephen D. Phinney and Jeff S. Volek.
Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study.
Cardiovascular Diabetology. 2018; 17:56 https://doi.org/10.1186/s12933-018-0698-8

[6] Gregory A Nichols, Sephy Philip, Kristi Reynolds, Craig B Granowitz, Sergio Fazio; Increased Cardiovascular Risk in Hypertriglyceridemic Patients with Statin-Controlled LDL Cholesterol, The Journal of Clinical Endocrinology & Metabolismhttps://doi.org/10.1210/jc.2018-00470

[7] Bartlett J, Predazzi IM, Williams SM, et al. Is Isolated Low HDL-C a CVD Risk Factor?: New Insights from the Framingham Offspring Study. Circulation Cardiovascular quality and outcomes. 2016;9(3):206-212. doi:10.1161/CIRCOUTCOMES.115.002436.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871717/

[8] Ballantyne CM, Olsson AG, Cook TJ, Mercuri MF, Pedersen TR, Kjekshus J. Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S.
Circulation. 2001 Dec 18;104(25):3046-51.
http://circ.ahajournals.org/content/104/25/3046

[9] Han BH, Sutin D, Williamson JD, Davis BR, Piller LB, Pervin H, Pressel SL, Blaum CS; ALLHAT Collaborative Research Group. Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older Adults: The ALLHAT-LLT Randomized Clinical Trial. JAMA Intern Med. 2017 Jul 1;177(7):955-965. doi: 10.1001/jamainternmed.2017.1442.

[10] Lloyd SM, Stott DJ, de Craen AJM, et al. Long-Term Effects of Statin Treatment in Elderly People: Extended Follow-Up of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Kiechl S, ed. PLoS ONE. 2013;8(9):e72642. doi:10.1371/journal.pone.0072642.

[11] Paul M RidkerEva LonnNina P. PaynterRobert GlynnSalim Yusuf. Primary Prevention With Statin Therapy in the Elderly: New Meta-Analyses From the Contemporary JUPITER and HOPE-3 Randomized Trials. 

[12] Bathum L, Depont Christensen R, Engers Pedersen L, Lyngsie Pedersen P, Larsen J, Nexøe J. Association of lipoprotein levels with mortality in subjects aged 50 + without previous diabetes or cardiovascular disease: A population-based register study. Scandinavian Journal of Primary Health Care. 2013;31(3):172-180. doi:10.3109/02813432.2013.824157.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750440/

 

3 thoughts on “The same old diet recommendations in New Zealand’s new cardiovascular disease prevention guidelines”

  1. Here’s an interesting aside on this – Kiwi Jocelyn Benatar and colleagues, who have done some very interesting work on dairy and cardiovascular disease in NZ, produced this meta-analysis of dairy feeding studies a few years back.
    In 8 studies on healthy volunteers, increasing dairy in the diet raised LDL a bit, P=0.05. It also lowered HDL a bit, non-significantly.
    In 12 studies on obese and overweight volunteers, increasing dairy had absolutely zero effect on LDL or HDL.
    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076480#pone-0076480-t002

    This sort of effect is well-known – we have not cherry picked the examples.

  2. “Is there an assumption that because everyone in NZ should be eating a high carb diet, there is no point giving advice to lower TGs?”

    That is exactly what I thought when I first heard of people in the UK no longer having their trigs tested, or reported.

    Even more appalling, I’ve read of diabetics being told to stop low carbing “and we can tell if you are complying because your trigs will increase”. Of course they are regarded as irrelevant because we don’t have a pill to decrease them.

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