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The new guidelines call for treating low-density lipoprotein cholesterol LDL-C levels in specific patient groups to lower goals than previously recommended.
They also support the use of coronary artery calcium scores and inflammatory markers to help clinicians better stratify risk. Another notable feature is that the guidelines call for special consideration when it comes to patients with diabetes or familial hypercholesterolemia, women, and pediatric patients with dyslipidemia. The Extreme Risk category includes patients who have progressive cardiovascular disease, such as patients with unstable angina who have achieved a lowered LDL-C level and patients who have established cardiovascular disease accompanied by diabetes mellitus, chronic kidney disease stages 3 or 4 , or familial hypercholesterolemia.
Recent Activity. Electronic address: parcdesalutmar. More parcdesalutmar. Affiliations 1. Find all citations in this journal default. Or filter your current search. Abstract Atherogenic dyslipidaemia is underdiagnosed, undertreated, and under-controlled. The aim of the present study was to assess the positioning of clinical guidelines as regards atherogenic dyslipidaemia.
High-density lipoprotein HDL cholesterol, triglycerides, atherogenic dyslipidaemia, non-HDL cholesterol, and apolipoprotein apo B were gathered from the 10 selected guidelines, and it was assessed whether these parameters were considered a cardiovascular risk factor, a therapeutic target, or proposed a pharmacological strategy. A detailed overview of risk assessment to guide decisions in whom to use statin therapy is provided in the Cardiovascular Protection in People with Diabetes chapter, p. Principles of risk assessment also are discussed in the Canadian Cardiovascular Society CCS Guidelines for the Management of Dyslipidemia 12,13 , and efforts were made to ensure consistency between the guidelines.
The burden of dyslipidemia is high in people with diabetes.
Therefore, a fasting lipid profile total cholesterol [TC], HDL-C, TG and calculated LDL-C should be conducted at the time of diagnosis of diabetes and if treatment is not warranted, the assessment should be repeated annually or as clinically indicated. If treatment for dyslipidemia is initiated, more frequent testing is warranted. Indeed, the most recent CCS guidelines for management of dyslipidemia now endorse the option of nonfasting lipid measurements more broadly, not solely in people with diabetes, unless the person is known to have abnormalities of TG.
In people known to have this level of hypertriglyceridemia, a fasting profile should be performed but non-HDL-C or apo B may still need to be used to determine atherogenicity of the dyslipidemia in this circumstance as well For screening in children and adolescents, please refer to the chapters dedicated to diabetes in these groups Type 1 Diabetes in Children and Adolescents chapter, p. S; Type 2 Diabetes in Children and Adolescents chapter, p. Healthy behaviour interventions remain a key component of CVD prevention strategies and of diabetes management in general.
Achievement of healthy weight and aerobic activity level, adoption of an energy-restricted, compositionally well-balanced diet that is low in cholesterol, saturated and trans fatty acids and refined carbohydrates, inclusion of viscous fibres, plant sterols, nuts and soy proteins, use of alcohol in moderation and smoking cessation all are fundamental considerations to improve glycemic control, the overall lipid profile and, most importantly, to reduce CVD risk 15— Each of these is discussed in more detail in accompanying chapters Physical Activity and Diabetes chapter, p.
S54; Nutrition Therapy chapter, p. S64; Weight Management in Diabetes chapter, p.
A number of studies and meta-analyses have shown that the degree of LDL-C lowering with statins and the beneficial effects of lowering LDL-C apply equally well to people with and without diabetes 27— Large trials have demonstrated the benefits of statin therapy in both the primary and secondary prevention of CVD, and subgroup analyses of these studies have shown similar benefits in subsets of participants with diabetes 28—30, Across all subgroups, statin therapy provides the same relative risk reduction in terms of outcomes, but the absolute benefit depends on the baseline level of absolute risk, which is typically increased in people with diabetes.
Intensive-dose statin has been demonstrated to improve outcome compared to moderate-dose statins, even in older people with MI or in people on dialysis 40— Therefore, statin use should be considered for any person with diabetes at risk of a CV event. In the very small group of lower-risk individuals with type 2 diabetes, the relative reduction in CVD risk with statin therapy is likely to be similar to that seen in those at higher global risk for CVD, but the absolute benefit from statin therapy is predicted to be smaller.
However, the global CVD risk of these individuals is lifelong, will increase with age and may be worsened in the presence of additional CV risk factors. Therefore, repeated monitoring of the CVD risk status of people with diabetes as outlined in the screening section above is recommended. These results emphasized the benefits of statin treatment irrespective of the pre-existing serum LDL-C level. The mean baseline LDL-C of the study population was 3. Treatment resulted in a mean LDL-C of 2. The absolute risk, determined by other risk factors in addition to LDL-C, should drive the target levels 32, Indeed, the investigators questioned whether any individual with type 2 diabetes can be considered at sufficiently low risk for therapy to be withheld Although originally designed as a secondary prevention trial, the protocol underwent several changes, including the addition of participants without known CAD and the eventual conversion of all participants with known CAD to open-label, lipid-lowering medication.
The composite primary endpoint was reduced by Notably, an increased event rate for all primary and secondary efficacy outcomes was noted in the subgroup with diabetes compared to the overall study population.
This finding provides yet further evidence that people with diabetes and CAD are at extremely high risk of subsequent CVD events. The proportional reductions were very similar in all subgroups, including those with diabetes without pre-existing vascular disease The mean LDL-C in the simvastatin plus ezetimibe arm was 1. The event reductions were particularly evident in people with type 2 diabetes In the vast majority of people, this target can be achieved with either a statin alone or a statin in combination with another lipid-lowering agent, such as ezetimibe, as shown in the IMPROVE-IT trial The study showed that LDL-C reductions with simvastatin plus ezetimibe were associated with reductions in the incidence of major atherosclerotic events vs.
People with diabetes who also have these features should be considered candidates for these agents as per CCS recommendations Subgroup analyses of these phase 2 and 3 studies of these agents suggest that subjects with diabetes have similar improvements in their lipid profile as do people without diabetes. Indeed, the first pivotal, secondary prevention trial using a PCSK9 inhibitor 53 and a prespecified subgroup analysis of the participants with concomitant diabetes 54 demonstrate further risk reduction with the combination of statin plus PCSK9 inhibitor when compared to statin alone.
In addition, there was no evidence of worsening of hyperglycemia in the participants with diabetes or of new onset diabetes in those without. Although it has not been studied in any event-based randomized clinical trial, colesevelam, a bile acid sequestrant, appears to have an ancillary effect on lowering A1C 55, Indeed, some studies suggest that their vascular risk is almost as high as individuals with existing type 2 diabetes 57,58 see Cardiovascular Protection in People with Diabetes, p.
No clinical trials of lipid-lowering agents have been conducted exclusively in people with impaired glucose tolerance IGT ; however, given their increased CVD risk, it is reasonable to consider treating this population to the same targets as people with diabetes To reduce the CVD morbidity and mortality associated with prediabetes and metabolic syndrome, an aggressive approach aimed at associated CVD risk factors, including dyslipidemia, is warranted.
Healthy behaviour interventions aimed at reducing the risk of developing both type 2 diabetes and CVD are essential. Even so, this dyslipidemia is relatively responsive to healthy behaviour interventions e. To reduce the residual CVD risk despite statin therapy, the potential benefit of additional lipid modification of high TG or low HDL-C with adjuvant pharmacotherapy has attracted tremendous interest.
Both of these second-line adjunctive therapies failed to show any added clinical benefit compared to statin therapy alone. Therefore, neither niacin or fibrates can be recommended as routine adjunctive therapy in people already meeting LDL-C targets with statins since these agents appear to have no additional impact on CVD endpoints.
Dyslipidaemia in Clinical Practice - CRC Press Book. Diabetologia. Jun;46(6) Epub May Diabetic dyslipidaemia : from basic research to clinical practice. Taskinen MR(1). Author information.
In some people, however, these agents may help achieve LDL-C goals The results of 4 recent meta-analyses examining the effects of fibrate therapy on CV outcomes found that fibrates may be particularly beneficial in people with atherogenic dyslipidemia, which is characterized by elevated TG, small LDL particles and reduced HDL-C 64— Evidence suggests that fibrate therapy may help reduce the microvascular complications associated with diabetes i.
For example, the Fenofibrate Intervention and Event Lowering in Diabetes FIELD study found that long-term treatment with fenofibrate reduced albuminuria and slowed estimated glomerular filtration rate loss over 5 years, despite initially and reversibly increasing plasma creatinine Furthermore, if residual hyper-TG is high enough to impart a risk of pancreatitis, fibrates may be warranted.
Triglyceride within the particles can then be hydrolyzed by LpL, which is found on the wall of capillaries. This concept is supported by the evidence from kinetic studies where acute fluctuations of plasma NEFA are not followed by concomitant changes in the production of total VLDL apo B. Close mobile search navigation Article Navigation. Screening The burden of dyslipidemia is high in people with diabetes. Diabetes is associated with a high risk of vascular disease i. Curr Cardiol Rep ;—
As indicated above, healthy behaviour interventions, including healthy eating, weight management and improved glycemic control, should all be emphasized. While several studies have shown that fibrate therapy is associated with CVD prevention, there is much less evidence for CVD risk reduction with fibrates relative to statins, specifically in people with diabetes 75— In some studies, no statistically significant reduction in the primary endpoint was demonstrated with fibrate therapy 80, But, as discussed above, the efficacy of these approaches in improving patient outcomes has not been established Although combination treatment with fenofibrate appears to be safe 61,80 , statins should not be used in combination with gemfibrozil due to an increased risk of myopathy and rhabdomyolysis When there is no overriding concern for acute pancreatitis and when there is evidence of hyper-TG in association with an elevated apo B or high non-HDL-C, it would be reasonable to consider a statin as first-line therapy with the subsequent addition of a fibrate, as needed.
As discussed above, evidence has emerged to support the use of apo B determination in the management of patients with dyslipidemia 12,13, Mechanistically, it is important to consider that there is 1 apo B molecule per LDL-lipoprotein a [Lp a ], very low-density lipoprotein VLDL and intermediate-density lipoprotein IDL particle, all of which are atherogenic. Consequently, the measurement of apo B and its monitoring in response to lipid-lowering therapy have been advocated by some authors 12,13,45, The measurement of apo B is most clinically useful in the individual with hyper-TG since it provides an indication of the total number of atherogenic lipoprotein particles in the circulation through direct measurement, as opposed to calculated LDL-C which cannot be determined reliably with TG above 4.
Because hyper-TG is commonly seen in people with diabetes, a focus on non-HDL-C or measurement of the apo B level can be used to guide therapy. The latter threshold is endorsed by the Canadian Cardiovascular Society Further important information has emerged from CARDS with respect to alternative targets and therapeutic goals In people treated with a statin, the average apo B concentration in the subgroup with concomitant LDL-C of 2.
A non-HDL-C level of 2. It should be recognized, however, that sole reliance on this general correlation would imply that all people have an average size of LDL-C which is clearly not the case. Thus, these correlations apply to populations and not necessarily to individual patients as LDL-C particle size may vary substantially, leading to the observed standard error associated with the linear correlation. But since non-HDL-C is available without additional cost or separate assay, it is attractive to consider, and its clinical use is supported by several analyses 89— Finally, because of a series of conflicting results from biochemical and genetic studies of HDL, and several apparently failed clinical trials that aimed to reduce CVD events by pharmacologically raising HDL 94 , there has been reconsideration of the targeting of HDL-C.
In summary, in order to reduce CVD risk among individuals with diabetes, it is important to understand the atherogenicity of small, dense LDL particles, remnant lipoproteins, TG-rich particles and the complex anti-atherogenic role of HDL particles. It is paramount to improve these metabolic parameters primarily through healthy behaviour interventions, improved glycemic control and pharmacotherapy, when indicated. Despite academic interest in various lipid parameters, it is of paramount importance to realize that the current best-outcome evidence for minimizing the atherogenic impact of lipid abnormalities in people with diabetes is to remain focused on achieving very low plasma concentrations of LDL-C, typically with statin-based therapy, as this conclusion is based on the most extensive clinical trial evidence.
Although statins are the cornerstone of lipid-altering therapy for CVD risk reduction in people with or without diabetes, recent evidence has suggested that chronic statin use is associated with an increased risk of incident diabetes. The interplay between statin therapy and incident diabetes was highlighted in a prespecified analysis of the West of Scotland Coronary Prevention Study WOSCOPS , which actually showed a decrease in the incidence of new-onset diabetes with pravastatin therapy Several meta-analyses suggest that there is indeed a small overall increase in diabetes with chronic statin use 98,99 and that this risk may be related to the statin dose The mechanistic link appears to involve inhibition of 3-hydroxymethylglutaryl-CoA reductase However, as discussed earlier, even people with risk factors for the development of diabetes enjoy a marked benefit in CVD risk reduction through the LDL-C lowering effects of statins, which appears to far outweigh any small risk of new-onset diabetes 57, Accordingly, these recent analyses do not affect the recommendation that statins are the preferred agents for lowering LDL-C in most instances, including in people with established diabetes or in those with risk factors for developing the disease , PLoS Med 6 6 : e For more information, visit www.
All content on guidelines. For questions, contact communication diabetes. Next Previous. Key Messages The beneficial effects of lowering low-density lipoprotein LDL -cholesterol with statin therapy apply equally well to people with diabetes as to those without the disease. Achievement of the primary goal may require intensification of healthy behaviour interventions with statin monotherapy. On occasion, the addition of other lipid-lowering medications may be required. Key Messages for People with Diabetes Most adults with diabetes are at greater risk for cardiovascular diseases, such as heart attack and stroke.
They have an even higher risk if their LDL-cholesterol is elevated. Adults with diabetes should have their cholesterol tested yearly or as indicated by your health-care provider. More frequent testing may be necessary for people taking cholesterol medications. Always discuss your cholesterol results with your physician or nurse practitioner and other members of your health-care team.
Introduction Diabetes is associated with a high risk of vascular disease i.
Risk Assessment of Individuals with Diabetes A detailed overview of risk assessment to guide decisions in whom to use statin therapy is provided in the Cardiovascular Protection in People with Diabetes chapter, p. Screening The burden of dyslipidemia is high in people with diabetes. Healthy Behaviour Interventions Healthy behaviour interventions remain a key component of CVD prevention strategies and of diabetes management in general.