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Strategies for cardiovascular disease prevention using diet modification and changes to the current food environment

  • Diet, both in terms of quality of food and drink and amount of calories consumed has the potential to reduce cardiovascular disease (CVD).
  • Food supplements are useful for some groups but eating a healthy diet is best.
  • Many factors effect food choice and these can be influenced by governmental and educational strategies.
  • Healthcare professionals need good nutritional knowledge and the interest and ability to promote healthy eating patterns for all age groups.

This review summarises the current evidence base for food groups and nutrients on CVD prevention and then explores the factors that influence individual food choice and the actions that can be put in place to help promote a healthy eating environment. Barriers to implementing change are also discussed.

Excess caloric intake is an important factor in cardiometabolic health; restricting calories improves insulin sensitivity, blood glucose and inflammation. Unfortunately, many people find significant sustained weight loss difficult to achieve but emerging evidence suggests that the quality of the diet consumed is important for avoiding overeating and that low-carbohydrate and Mediterranean diets are superior to low fat diets for maintaining a healthy weight.

The article outlines the evidence for a healthy diet;

  • Food supplementation overall has not shown a significant reduction in CVD therefore dietary recommendations for CVD prevention should focus on whole foods and diet quality.
  • Consuming fruit and vegetables reduces CVD risk. This is thought to be due to phytochemicals and micronutrients in fruit and vegetables such as folate, potassium, fibre and flavonoids.
  • The consumption of whole grains reduces CVD risk. This is because the bran and germ layers (which are removed from refined grains) are a rich source of fibre, lignans, micronutrients, fatty acids and other phytonutrients. As a result whole grain consumption generally results in a high sense of satiety and a lower glycemic response when compared with refined grains.
  • Marine fish are a rich source of omega-3 fatty acids which can reduce arrhythmias, thrombosis, inflammation, blood pressure and improve lipid ratios thereby reducing CVD risk.
  • Nuts and legumes are high in unsaturated fat, fibre, micronutrients and phytochemicals which can reduce CVD risk.
  • Processed red meats increase the risk of CVD due to bioactive molecules such as haem iron, sodium, nitrates and L-carnitine which can cause increased blood pressure, oxidative stress, lipid peroxidation and unfavourable changes to the gut microbiome.
  • Alcohol shows a ‘u-shaped’ relationship with CVD risk where both abstainers and heavy drinkers have an increased risk of CVD when compared with moderate drinkers.
  • Sugar sweetened beverages increase the risk of CVD in a dose dependent manner.
  • Regular coffee drinking (3-5 cups a day) and regular tea drinking can lower CVD risk.

The article further looks at drivers for a poor-quality diet and actions necessary at all societal levels to achieve a cardio-protective diet. Drivers of poor diet quality include lack of knowledge, lack of availability, the pricing of food, time scarcity, social and cultural norms, marketing and taste.

Examples of actions across society that can be used to improve a population’s diet include:

  • Making cardiovascular disease a global priority
  • Nutritional and agricultural policies
  • Nutritional labelling
  • Regulation of marketing
  • School and workplace interventions
  • Standards of education and care in nutrition for health care professionals
  • Individual behavioural change.

One of the strengths of this article is that it explores the biological, physical, social and psychological factors that influence why people make certain dietary choices and recognises that scientific evidence alone is not enough to change the food a population consumes. The authors conclude :

‘A concerted effort from all levels of society will be needed to fundamentally change the current food environment and the global food system.’

For further information see: Yu E, Malik V and Hu F 2018 Cardiovascular disease prevention by diet modification. JACC 72,8:914-26

Raised LDL cholesterol is associated with increased cardiovascular disease mortality in individuals at low 10-year CVD risk

Raised low-density lipoprotein cholesterol (LDL-C) is associated with increased cardiovascular disease mortality (CVD) in individuals at low 10-year CVD risk.

  • This large long-term study has shown that raised levels of LDL-C (and also non HDL-C) increases the risk of CVD mortality even in people with a low 10-year CVD risk.
  • A key strength of this study is that 36 375 individuals were followed-up for more than 2 decades.
  • Further work is still required to see if a lipid-lowering diet, lifestyle and pharmacological interventions will affect CVD outcomes in this low risk group of people with raised LDL-C and non-HDL-C.

In this US based study, 36 375 participants, from the Cooper Center Longitudinal Study (CCLS) cohort, with no history of CVD or diabetes mellitus and estimated to be of low 10-year CVD risk (< 7.5%), were included in a long-term assessment of the impact of raised LDL-C and non-HDL-C (defined as total cholesterol minus HDL cholesterol) on CVD mortality. Participants were only included if they had lipid measurements recorded during the 1978-1998 time period to minimise any impact from being on lipid lowering therapy which was more commonly used after this time.

Nearly three quarters of the participants (72%) were males with a median age of 42 years; they were followed-up over a median of 26.8 years and during this time 1086 CVD and 598 coronary heart disease deaths were recorded.

LDL-C and non-HDL-C of greater or equal to 160 mg/dL were found to be independently associated with an increase of 50% to 80% in relative risk of CVD mortality. This increased risk remained also in a subset of individuals with an estimated 5% 10-year CVD risk. Non-HDL-C appeared to be also important for long-term CVD risk in addition to LDL-C. It can be measured at no extra cost to LDL-C and is considered to be potentially a more robust prognostic marker. There were not enough women in the study to assess statistical differences in CVD mortality but generally similar patterns of elevated risk were observed with both sexes.

This study is of particular interest because of its large-scale, long-time follow-up and especially the fact that it focuses on low (10-year) CVD risk people. Much of the evidence for lipid management and CVD risk is in individuals at intermediate and high risk of CVD.

Although this observational study does not provide direct evidence that lowering LDL-C will improve outcomes in low CVD risk populations, it adds to the discussion to consider appropriate LDL-C thresholds for lipid lowering interventions in people who are estimated to be of low CVD risk. Further research is needed to define lipid lowering strategies in low CVD risk individuals with elevated LDL-C and non-HDL-C levels.

For further information see:  Abdullah SM, Defina LF and Leonard D et al The Cooper Center Longitudinal Study  2018  Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease. Circulation 138 DOI:10.1161/CIRCULATIONAHA.118.034273

A low-fat spread enriched with plant sterols and fish omega-3 fatty acids significantly lowers triglyceride and LDL-cholesterol levels in healthy individuals who have moderately raised blood cholesterol

  • This study showed that consuming daily a low- fat spread with 2 g added plant sterols and 1 g fish omega-3 fatty acids over 4 weeks significantly lowers blood triglyceride (TG) and LDL-cholesterol levels. 
  • Consuming a low-fat spread with added plant sterols and fish omega-3 fatty acids as part of a healthy, balanced diet may help individuals to maintaining low TG and LDL-C concentrations and so help to reduce their overall cardiovascular (CVD) risk.

This randomised, double-blind, placebo-controlled, parallel group study (conducted in Berlin, Germany) followed 260 participants (aged 18-75 years) who, after a 2 week placebo run-in period, were allocated to receive for four weeks either a low-fat spread with 1 g/d of eicosapentaenoic acid (EPA) and docosahexanoic acid (DHD) from fish oils and 2 g/d of plant sterols or a placebo low-fat spread.

The study group had moderately elevated blood TG of (≥1.4 mmol/L and low density lipoprotein cholesterol (LDL-C) of ≥3.4 mmol/L. Fasting lipid levels as well as apolipoproteins (Apo) were measured at the end of the two week run-in and at the end of the four week intervention periods.

Individuals in the intervention group of the study benefited from significant reductions in both TG (10.6% reduction) and LDL-C (5.2% reduction) levels when compared with the placebo group. There was also a significant reduction in total cholesterol, non-high density lipoprotein (non-HDL-C), remnant cholesterol and Apo B, Apo AII and ApoCIII levels when compared with placebo. No significant difference was seen in HDL-cholesterol,  and other apolipopreotin concentrations.

In this study the daily low-fat spread portion was consumed over at least two main meals and this appears to lead to a better effect than in studies where a single daily intake was given.

The decrease in elevated blood TG next to the LDL-C lowering with the combined intake of plant sterols and fish oils is particularly interesting as elevated blood TG are an emerging risk factor in the development of atherosclerosis and cardiovascular disease (CVD). Lifelong management of LDL-C and TG levels is seen as important to reduce life time CVD risk and hence early, easy to use interventions are needed.

For further information see: Blom WAM, Hiemstra H et al. 2018 A low-fat spread with added plant sterols and fish omega-3 fatty acids lowers serum triglycerides and LDL-cholesterol concentrations in individuals with modest hypercholesterolaemia and hypertriglyceridaemia. European Journal of Nutrition https://doi.org/10.1007/s00394-018-1706-1

Phytosterol supplementation may play a role in reducing low density lipoprotein (LDL) cholesterol, elevated liver enzymes and some markers of inflammation for patients with non-alcoholic fatty liver disease

  • Non-alcoholic fatty liver disease (NAFLD) is an important global health problem and its prevalence is growing as part of the current obesity epidemic
  • This exploratory study found that a 1.6 g/d supplement of phytosterols (plant sterols or stanols) taken for 8 weeks was effective in lowering LDL cholesterol (LDL-C), elevated liver enzymes and some markers of inflammation
  • This study suggests a benefit of phytosterols for NAFLD patients, but larger and longer-term studies are needed to confirm the results

It is estimated that non-alcoholic fatty liver disease (NAFLD) has an impact on the health of 25-30% of the general population1,2. NAFLD can lead to liver damage such as liver fibrosis and cirrhosis as a result of inflammatory processes from increased fat around the liver.

This exploratory, randomised, double-blind, placebo-controlled clinical  study, set in Iran, investigated the effectiveness of phytosterol supplementation in helping to control disease markers for inflammation and liver damage as well as LDL-C in patients with NAFLD.  Fasting blood samples were taken at baseline and then again at the end of the study at eight weeks. Thirty eight patients (who had been diagnosed by ultrasound with NAFLD) were included and were divided into a control and placebo group. The control group were given a starch tablet as a placebo supplement whilst those in the active arm of the study received an oral supplement of 1.6 g of phytosterols in the form of a daily capsule.

The daily intake of 1.6 g of phytosterol supplementation in patients with NAFLD significantly reduced serum levels of LDL-C, the liver enzymes AST and ALT and the inflammatory marker TNF-a but did not affect other cholesterol measures (e.g. high density lipoprotein, triglycerides, cholesterol ratios), other liver enzymes (GGT), other inflammatory markers (IL-6, hs-CRP) or hormones regulating energy use within the body (leptin) and the formation of fatty deposits in the arteries (adiponectin).

It is assumed that these exploratory findings will lead to further research into the role of phytosterols in the treatment of NAFLD. Of note, this study enrolled a limited numbers of participants and was carried out over just 8 weeks. Larger and longer-term studies are needed.

References

  1. Vernon G, Baranova A and Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Ailment Pharmacol Ther. 2011;34:274-85.
  2. Riqueline a, Arrese M, Soza A et al. Non-alcoholic fatty liver disease and its association with obesity, insulin resistance and increased serum levels of C-ractive protein in Hispanics. Liver Int.2009:29:82-88

For further information see: Javanmardi MA, Mohammad shahi M, Seyedian SS et al 2018 Effects of phytosterol supplementation on serum levels of lipid profiles, liver enzymes, inflammatory markers, adiponectin and leptin in patients affected by Non-alcoholic fatty liver disease: A double-blind, placebo-controlled, randomized clinical trial. Journal of the  American College of Nutrition https://doi.org/10.1080/07315724.2018.1466739

Individuals with or at risk of developing type 2 diabetes mellitus can achieve a reduction in elevated triglycerides and LDL- cholesterol by consuming 2 g of plant sterols daily.

  • Having type 2 diabetes mellitus (T2DM) doubles the risk of an individual developing cardiovascular disease (CVD) when compared to those without the disease. 
  • Reducing CVD risk factors such as elevated blood cholesterol and trilglyceride (TG) levels is vital as CVD is the major cause of death in people with T2DM.
  • This randomised, double-blind, placebo- controlled study showed a dual blood lipid lowering benefit from the daily consumption of a low-fat spread enriched with 2 g of plant sterols in people with or at risk of developing T2DM and raised blood cholesterol and TG levels .

Reducing the risk of CVD in individuals who have or who are at risk of T2DM is crucial. This double-blind, randomised, placebo-controlled, parallel study, set in Australia, studied dyslipidaemic individuals  with T2DM or at risk of developingT2DM and assessed the impact of six weeks intake of a low-fat spread enriched with plant sterols (PS) on elevated low-density lipoprotein cholesterol (LDL-C) and TG.

After a two week run-in period the 161 study participants consumed low-fat spread with 2 g of added PS or placebo low-fat spread daily for a six week period. Fasted total cholesterol (TC), LDL-C, TG and high-density lipoprotein cholesterol (HDL-C), glucose and insulin were measured at baseline and after the 6-week intervention period. In the 138 individuals included in the per protocol analysis a significant reduction of 4.6 % in LDL-C and 8.3 % in TG was observed in the group consuming 2 g of plant sterol enriched low-fat spread compared with the control. All other measures were the same between the placebo and plant sterol groups.

Only 13 participants were excluded for low compliance rates with the test product and the low-fat spread was generally well tolerated.

The study demonstrates that a low-fat spread with added PS has a dual blood lipid benefit with a reduction in both elevated TG and LDL-C. PS, as part of a healthy balanced diet, may offer an effective option for those with or at risk of developing T2DM in helping to manage dyslipidaemia and reduce overall CVD risk.

For further information see: Trautwein EA, Koppenol WP and de Jong A et al. 2018 Plant sterols lower LDL-cholesterol and trigylcerides in dyslipidemic individuals with or at risk of developing type 2 diabetes; a randomized, double-blind, placebo-controlled study. Nutrition & Diabetes 8:30 DOI 10.1038/s41387-018-0039-8.

Progress and perspectives in plant sterols and plant stanol research

This review represents the Proceedings of a scientific meeting with 31 experts known as the 3rd International Plant Sterols/Stanols, Health and Disease Conference that took place from Sept 30 – Oct 1, 2016 in Winnipeg, Canada. This 2-day meeting was the third of a series of plant sterol/stanol expert meetings after previous expert meetings in 2001 (Katan et al, Mayo Clin Proc 2003) and 2011 (Plat et al Atherosclerosis 2012).

Day 1 focused around topics addressing physiological aspects of plant sterols/stanols; on day 2 clinical aspects related to cardiovascular disease (CVD) risk, disorders related to intestinal plant sterol/stanol absorption next to case reports on the genetic disease phytosterolemia (also known as sitosterolemia) were presented. Specific topics included the cholesterol-lowering effect next to health benefits of plant sterols/stanols beyond cholesterol lowering, their role as adjuncts to diet and drug treatment and challenges involved in measuring plant sterol/stanol concentrations in biological samples. Further, inter-individual responses to plant sterol/stanol intake and the role of personalizing lipid-lowering therapies were discussed and lastly the clinical aspects and treatment of phytosterolemia were reviewed.

Key insights discussed at the expert meeting are:

  • Regarding the cholesterol lowering effect of plant sterols/stanols, data summarized from meta-analyses show that most studies reported an LDL-cholesterol (LDL-C) reduction between 0.3 and 0.4 mmol/L, equivalent to about a 7.5-12% lowering. As LDL-C is recognized as a causal CVD risk factor, such a lowering of LDL-C would correspond to a 7% reduction in risk. However, direct evidence of an effect on CVD is not available, as studies on CVD events and mortality are lacking, likely because they are expensive and challenging with respect to long-term compliance.
  • The advantages of combining plant sterols/stanols with other dietary means such as dietary fiber, soy protein, and nuts are becoming more widely recognized.
  • Concerning benefits of plant sterols/stanol beyond cholesterol-lowering, promising triglyceride (TG)-lowering and immune-modulating effects were discussed, but further human studies are needed to further substantiate these effects.
  • Effects of plant sterols/stanols on the central nervous system suggest that they do not enhance cognition in normo-cognitive settings, although there is emerging evidence supporting a therapeutic potential for plant sterols in disease-related cognitive impairment.
  • Regarding the responsiveness of LDL-C lowering to plant sterols/stanols, several cholesterol related gene-diet interactions have been found. Further studies will help to better understand inter-individual variability and may lead towards more personalized approaches.
  • Differences in the responsiveness may be explained by differences in cholesterol absorption and synthesis efficiency. The reciprocity between cholesterol synthesis and absorption on the LDL-C lowering efficacy of plant sterols/stanols is increasingly been recognized.
  • Concerning plant sterols/stanol and the risk of CVD, clear evidence for effects on surrogate markers of CVD risk, e.g. on vascular function is still inconclusive. No worsening of endothelial function has however been shown.
  • The difference in the severity of phytosterolemia across patients was emphasized and the importance of an appropriate screening using circulating plant sterol concentrations and confirmation of the specific gene mutation as diagnostic criteria was emphasized. Diagnosis of phytosterolemia should be considered in individuals with a hyper-response to dietary sterol (cholesterol and plant sterols) intake.

Although the clinical benefits of dietary plant sterols and stanols to vascular function have yet not been established and long-term clinical trials with endpoints of CVD are still lacking, the review concludes that plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management and serve as important natural health products as well as ingredients of functional foods.

Progress and perspectives in plant sterols and plant stanol research, Jones et al Nutrition Reviews 2018; doi: 10.1 093/nutritinuy032

 

A plant stanol-enriched smoothie drink lowers blood cholesterol in an Indonesian population

  • A clinical study has demonstrated that a smoothie drink with 1 gram of added plant stanols, taken twice daily after meals, lowers blood total and low- density lipoprotein cholesterol (LDL-C) in Indonesian adults with raised cholesterol.
  • The effect was seen within two weeks of taking the plant stanols and was maintained over the four-week study period.
  • This study is important because it expands the evidence for the LDL-C lowering benefit of plant stanols to an Indonesian population with different dietary patterns.
  • The study also demonstrates the usefulness of adding plant stanols into a smoothie drink.

The prevalence of cardiovascular disease (CVD) in the Indonesian population is rising1 and accounts for 37% of all deaths in Indonesia 2. The major risk factors for CVD in Indonesia are similar to that of the rest of the world; elevated blood pressure, elevated blood cholesterol and cigarette smoking1.  Finding practical ways to help reduce overall CVD risk is important especially through primary prevention with diet and lifestyle3.

This randomised, double blind, placebo controlled, parallel design, trial tested the effects of dietary advice and twice daily consumption of a plant stanol ester enriched smoothie drink on the blood lipid profiles of 99 Indonesian adults with hypercholesterolemia. Study participants were divided into two groups with fifty receiving a control smoothie drink and the remaining 49 receiving the plant stanol ester-enriched smoothie drink (2 g plant stanols per day); all received also dietary advice. A serving (100 ml) of the smoothie drink was consumed immediately after the main morning and evening meal each day. Clinical, anthropometric, and biochemical variables including blood lipids were measured at baseline, 2 weeks and 4 weeks.  The dietary advice delivered by two trained dieticians was based upon Indonesian Heart Foundation recommendations.

Compared with the control group, the group consuming the smoothie drink  with added plant stanols reduced their serum LDL-C concentration by 7.6%(p<0.05) and 9.0% (p<0.05) over two and four weeks, respectively.

In comparison with the habitual baseline diet, LDL-cholesterol was reduced by 9.3% (p<0.05) and 9.8% (p<0.05) at two and four weeks respectively in the active arm of the study.

Adverse events were generally mild gastrointestinal effects and no difference was detected between the two groups.

This is the first study to demonstrate the efficacy of plant stanols in lowering LDL-C for the Indonesian population. The reported effect is similar to that already demonstrated in other populations. The study also demonstrates that plant stanols are effective in a non-fermented smoothie drink. It adds to the growing wealth of evidence supporting the use of plant stanols and sterols in reducing LDL-C, a key modifiable risk factor for CVD.

References

  1. M.A.Hussain, A.A. Mamun, S.A.E. Peters et al. The burden of cardiovascular disease attributable to major modifiable risk factors in Indonesia. Journal of Epidemiology 2016: 26, 10 515-521
  2. World Health Organization , Noncommunicable Diseases (NCD) Country Profiles 2014 http://www.who.int/gho/countries/idn/country-profiles/en/.
  3. Expert Panel on; Dyslipidemia, S.M. Grundy, H. Arai et al., “An International Atherosclerosis Society position paper, Global recommendations for the management of dyslipidemia:Executive summary; Expert Panel on Dyslipidemia, Atherosclerosis, 2014 232, 410-413

 

For further information see: Lestiani L, Chandra DN, Laitinen K et al Double-Blind randomized Placebo Controlled Trial Demonstrating serum Cholesterol Lowering Efficacy of a Smoothie Drink with added plant stanol esters in an Indonesian population Hindawi Cholesterol 2018  published online @ https//www.hindawi.com/journals/cholesterol/2018/4857473/

Cost-effectiveness of foods with added plant sterols or stanols as a primary prevention strategy for people with CVD in England

Yang et al “The effectiveness and costeffectiveness of plant sterol or stanolenriched functional foods as a primary prevention strategy for people with cardiovascular disease risk in England: a modeling study”.
Eur J Health Econ; DOI 10.1007/s10198-017-0934-2

  • This new publication evaluates the cost-effectiveness of consuming margarine-type spreads with added plant sterols or stanols for the prevention of cardiovascular disease (CVD) in people with hypercholesterolemia in England as compared to a normal diet.
  • This study therefore adds to available evidence from previous studies on whether the use of plant sterols/stanols is a cost-effective preventive strategy for reducing CVD risk, especially from an United Kingdom (UK) context.
  • It was found that daily intake of spreads with added plant sterols or stanols could reduce CVD risk, esp. in men and older age groups. Assuming a 50% compliance rate, over a period of 20 years 69 CVD events per 10,000 men and 40 CVD events per 10,000 women aged 45-85 years could be saved.
  • If the costs to the consumers between a typical spread and a plant sterol- or stanol-added spread is subsidized, the intake of plant sterols or stanols from spread is likely to be cost-effective over 20 years for hypercholesterolaemic men aged over 64 years and for hypercholesterolaemic women aged over 74 years with a compliance level of either 10 or 50% and assuming a cost-effectiveness threshold of £30,000 per QALY gained.
  • The findings from this assessment suggests that encouraging consumers to use foods with added plant sterols or stanols is likely to bring cost savings to national health systems next to improving health outcomes.

This new analysis by Yang et al. assessed the cost-effectiveness of plant sterol- or stanol-added foods took for the prevention of CVD in an English population with elevated total cholesterol (TC). The analysis took the perspective of the British National Health Service (NHS). The population cohort used for the analysis was from the 2011 Health Survey for England including 2238 individuals with elevated TC (1598 with TC of 4-6 mmol/L and 640 with TC above 6 mmol/L). Reported health outcomes included CVD events, mortality, and quality-adjusted life years (QALYs). Cost-effectiveness was defined based on available UK criteria with a threshold of between £20,000 and £30,000 per QALY gained. Effectiveness outcomes were assessed for 10-year CVD risk of individuals with either mild (4-6 mmol/L) or high (above 6 mmol/L) TC and by gender and age groups (45–54, 55–64, 65–74, 75–85 years) and for CVD events avoided and QALY gains over 20 years.

Regarding the effect size, a 12% reduction in TC or LDLC with an intake of 3 g/d of plant sterols or stanols was assumed.

The analyses were based on plant sterol- or stanol-added spreads and not on other food formats because the required intake of 3 g/d can be best achieved with spreads, they are commonly consumed in the English diet and are the least expensive means of providing the required daily intake.

Regarding cost-effectiveness and if the NHS would pay the costs for the plant sterol- or stanol-added spreads, the probability that these foods are cost-effective was seen as 100% for men over 64 years and for women over 74 years in the high cholesterol group (total cholesterol above 6 mmol/L) and at £20,000 per quality-adjusted life years QALYs).  It is also below the £30,000 threshold for men over 54 women over 64 years of age.

Subsidizing plant sterol or stanols added spreads was found to be more cost-effective in individuals with higher TC levels; QALY gains increased with the level of compliance (10 vs. 50%) and with older age of men and women.

Shifting the cost burden of paying for the plant sterol- or stanol-added spread to the consumers, increases the cost-effectiveness and the NHS will benefit from reduced CVD treatment costs.

Overall, this new cost-effectiveness assessment focusing on the UK perspective adds to previous analyses from e.g. Germany, Finland and Canada showing that significant cost savings in health care costs could be achieved with the regular consumption of foods with added plant sterols or stanols next to a potential reduction in CVD cases.

Low density lipoprotein cholesterol levels currently considered normal are associated with subclinical atherosclerosis in the absence of cardiovascular risk factors

  • Individuals without cardiovascular (CV) risk factors are normally considered low risk for atherosclerosis and cardiovascular disease (CVD) and yet they still have CV events.
  • Subclinical atherosclerosis may be found in approximately half of middle aged individuals without major conventional CV risk factors and in around a third of those who have optimal risk factor profiles.
  • Low density lipoprotein cholesterol (LDL-C) even at levels currently considered normal can predict subclinical atherosclerosis in individuals free of CV risk factors.
  • This finding supports more effective LDL-C lowering strategies to prevent early development or progression of atherosclerosis.

To gain greater understanding of predictors of subclinical atherosclerosis (e.g. plaque or coronary artery calcification) in individuals free of cardiovascular (CV) risk factors, participants from the PESA (Progression of Early Subclinical Atherosclerosis) study, without conventional CV risk factors, were evaluated. Out of a total 4184 participants in the PESA study 1779 were assessed as being CV risk factor free. The 4184 PESA participants were middle-aged men and women between 40 to 54 years.

Cardiovascular (CV) risk factor free was defined as:

  • No current smoking
  • Untreated blood pressure less than 140/90 mmHg
  • Fasting glucose less than 126 mg/dl
  • Total cholesterol (TC) less than 240 mg/dl
  • Low-density lipoprotein cholesterol (LDL-C) less than 160 mg/dl
  • High density lipoprotein cholesterol (HDL-C) greater than or equal to 40 mg/dl

 

A sub group of 740 people with optimal CV risk factors was also identified based on blood pressure levels less than 120/80 mmHg, fasting glucose less than 100 mg/dl, glycosylated haemoglobin (HbA1c) of less than 5.7% and TC less than 200 mg/dl.

Ultrasound detected plaques; coronary artery calcification; serum biomarkers and lifestyle adjusted odds ratios were measured. Subclinical atherosclerosis (plaque or coronary artery calcification) was found in nearly half of the participants free of CV risk factors (49.7%).  In the group with optimal CV risk factors, 37.8% had atherosclerosis.

Along with unmodifiable risk factors such as age and male sex the modifiable risk factor serum LDL-C was found to be independently associated with the presence and extent of atherosclerotic changes in both the CV risk factor free and optimal CV risk factor groups. Increased LDL-C levels demonstrated a linear and significant rise in the prevalence of atherosclerosis from an 11% increase in the 60-70 mg/dl LDL-C category to a 64% in the 150 to 160 mg/dl LDL-C group.

This study supports a more aggressive strategy to lower LDL-C. It gives further strength to the argument for “the lower the better” and “the earlier the better” when it comes to LDL-C levels. The LDL-C levels in the sub populations analysed were well within the range that is considered normal which reinforces the concept that in fact healthy LDL-C concentrations are probably much lower than those that are currently recommend. This study provides evidence of a unique and independent role for LDL-C in the early development of atherogenesis and has important implications for cardiovascular disease prevention. A healthy diet and lifestyle including the LDL-C lowering benefit of plant sterols/stanols as part of dietary options can help in maintaining LDL-C levels at low levels through the lifetime.

References

For further information see: Fernández-Friera L, Fuster V and López-Melgar B et al  2017 Normal LDL-Cholesterol levels are associated with subclinical atherosclerosis in the absence of risk factors. Journal of American College of Cardiology 70, 24, 2979-2991.

Diabetes UK “Evidence-based nutrition guidelines for the prevention and management of diabetes” recommend plant sterols/stanols for cholesterol management

Diabetes UK “Evidence-based nutrition guidelines for the prevention and management of diabetes” recommend plant sterols/stanols for cholesterol management

 

  • Diabetes UK recommends that health care professionals take an individualised approach when talking to people with or at risk of developing diabetes.
  • Key diet and lifestyle recommendations include restriction of energy intake, reduction in total and saturated fat intake, increase in dietary fibre intake and more physical activity
  • Diabetes UK state that a daily dose of 2-3 g of plant sterols and stanols can be recommended as part of a healthy diet to reduce cardiovascular risk for people with or at risk of developing diabetes.
  • Plant sterols and stanols are also recommended for people already taking cholesterol-lowering medication to further reduce their serum cholesterol and cardiovascular risk.

Updated evidence-based nutrition guidelines for the prevention and management of diabetes have been published by Diabetes UK in March 2018. The guidelines written for health care professionals (HCPs) are aimed at adults with either Type 1 or Type 2 diabetes and those at risk of developing Type 2 diabetes.

The guidelines recommend that HCPs take an individualised approach to diet and consider a person’s personal and cultural preferences. They recommended people eat more vegetables, fruits, wholegrains, fish, nuts and pulses.

To reduce the risk of cardiovascular disease (CVD) and in particular two of the modifiable risk factors, blood lipids and blood pressure, the guidelines recommend Mediterranean or DASH-style diets with less salt, more plant based food and less red and processed meat, refined carbohydrates and sugar sweetened drinks. They recommend replacing saturated fats with unsaturated fats and to limit the intake of trans fatty acids (TFA). They also recommended limiting alcohol intake to less than 14 units per week. Overweight individuals should aim to achieve modest weight loss of at least 5% of overall weight and everyone should aim for at least 150 minutes per week of moderate to vigorous physical exercise, over at least three days. A daily dose of 2-3 g of plant stanols and sterols per day can be recommended.

Whilst acknowledging that the UK NICE guidelines have not recommended the use of plant sterols and stanols for the primary prevention of CVD (mainly due to the lack of hard cardiovascular event endpoint studies) Diabetes UK clearly recommend their use at a daily dose of 2-3 g per day. Diabetes UK cites evidence of the effectiveness of plant sterols and stanols in significantly reducing total and LDL cholesterol in people with or without diabetes and also explain that further reductions in LDL-C can also be achieved in people on cholesterol lowering medication such as statins.

 

For further information see: https://www.diabetes.org.uk/professionals/position-statements-reports/food-nutrition-lifestyle/evidence-based-nutrition-guidelines-for-the-prevention-and-management-of-diabetes