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Viewpoint: Cardiovascular risk management in type 2 diabetes
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Endocrine Today interviews Kathleen M. Dungan, MD, Assistant Professor of Medicine, Division of Endocrinology, Diabetes, & Metabolism, at Ohio State University in Columbus, Ohio. Part 1 of a 2-part series.
According to a 2010 article in Diabetes Care, 70% of patients with type 2 diabetes will die of cardiovascular causes. However, many patients with type 2 diabetes do not realize their heightened CV risks. What is the correlation between type 2 diabetes and risk for CV disease?
Type 2 diabetes is widely regarded as a coronary risk equivalent. Patients with type 2 diabetes who do not have CVD have about the same risk for a mild myocardial infarction (MI) or other CV event as patients with coronary artery disease who do not have diabetes. Patients with diabetes who also have CVD have an increased risk for a subsequent CV event. Furthermore, patients with prediabetes have an increased CV risk.
There does not seem to be a clear association between hyperglycemia and increased risk. Therefore, when determining the risk for MI or other CV event, attention should center on other risk factors rather than glucose alone.
Type 2 diabetes is also considered a gender-equalizer in terms of CV risk: Whereas women in general have less risk for CVD than men, women with diabetes have the same risk for an MI or CV event as men. Men and women have similar risks for developing diabetes.
Studies show that lowering blood pressure is one way to lessen risk for CVD in patients with type 2 diabetes. What is the physician's approach to safely and effectively lower elevated blood pressure in a patient with type 2 diabetes?
The blood pressure target for patients with type 2 diabetes is less than 130/80 mm Hg, and the range for patients who do not have type 2 diabetes is higher than that.
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The first-line agents used in lowering blood pressure are angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers because they are associated with a reduced risk for nephropathy and progression of nephropathy, and they are cardioprotective. However, a variety of agents have been shown to reduce CV events, including beta-blockers, calcium channel blockers and thiazide diuretics. Therefore, the best choice for a second-line therapy is not as clear, and multiple agents may be needed for effective blood pressure control.
Safely and effectively lowering a patient’s blood pressure requires continuous vigilant attention because blood pressure can change over time and both patients and providers can become complacent when monitoring it. Unlike glycemic control, blood pressure control offers positive CV benefits regardless of disease stage. Therefore, providers must continuously be vigilant in their efforts to maintain blood pressure control.
It is important for patients to monitor their own blood pressure, but they should not overinterpret the results. Many patients mention having "white coat" syndrome (ie, when blood pressure rises only in a medical or clinical environment); however, studies that show benefits of controlling blood pressure are based on data derived from monitoring blood pressure in an office setting. Although physicians should consider that a patient’s blood pressure may only be elevated in the clinician's setting, they should also consider the results of studies in which consistent blood pressure readings were obtained in a clinical setting.
How does low-density lipoprotein (LDL) cholesterol affect patients with type 2 diabetes?
Patients with type 2 diabetes have smaller, denser LDL particles, which are more easily oxidized, making them more atherogenic. Even though the overall concentration of LDL is not elevated compared with that in patients without diabetes, an overall greater number of LDL particles translates to increased atherosclerosis because it is the lipoprotein particle that crosses the endothelial barrier, not the actual LDL molecule. Therefore, the target LDL is more stringent in patients with diabetes. Therefore, lowering LDL should be the primary focus of lipid management, although nontraditional measures, such as non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, and detailed lipoprotein particle levels are gaining increased attention as possible alternatives for lessening the risk for CVD. Further study on LDL targets in patients with type 1 diabetes is needed.
The National Cholesterol Education Program guidelines advocate a target LDL level of less than 100 mg/dL for patients with diabetes similar to the guidelines for patients with known CVD or coronary risk equivalents (Framingham risk score >20%). Increasing evidence recommends an even lower target (<70 mg/dL) for patients with diabetes who have known CVD.
What is the role of statins in the treatment of patients with type 2 diabetes?
Due to the complexities of lipid abnormalities that are not well characterized by standard lipid panels and to other purported beneficial pleiotropic effects of statins, patients with type 2 diabetes and CVD who are 40 years or older with at least one other risk factor should receive a statin regardless of baseline LDL level. Treatment for patients younger than 40 years who do not have other risk factors and do not have elevated LDL has not been determined. However, the general treatment consensus is moving toward treating almost all patients with type 2 diabetes with a statin, regardless of baseline LDL level.
Patients who do not reach therapeutic targets at the highest tolerable dose may need a more potent statin, such as atorvastatin or rosuvastatin, or use a combination therapy. Even a low dose of statin, used with or without another agent (eg, Niaspan, fibrate, ezetemibe or bile acid sequestrants), is preferable to monotherapy with other agents because evidence supports its success in reducing CV risk. However, combination therapy may be associated with increased risk for side effects (primarily myalgia and myopathy or rhabdomyolysis, and the potential for gastrointestinal and hepatotoxic effects), and its use is not as well supported by evidence. Statin treatment must be individualized. Not all patients will tolerate high-dose statins, and in some patients, LDL levels may not decrease to the desired target.
How long should it take to reduce a patient’s LDL level using statin treatment?
A 3-month lifestyle evaluation for patients with modestly elevated LDL should be implemented, particularly for patients who are not at high risk for a CV event. If lipid panels are measured at each visit, then the physician can actively adjust the dose. CVD takes years to develop, and although many of these patients have CVD at baseline, data do not suggest that physicians must immediately lower LDL level in patients who have not had a CV event. Conversely, data also suggest that multifactorial risk factor modification including the use of statins can cause regression of atherosclerotic lesions.
For example, it would be difficult to reduce a patient’s LDL level by more than 50% if the baseline is 200 mg/dL. The physician can use high-dose statins to determine a patient’s response, but an LDL level of less than 70 mg/dL may not be attainable without untoward previously mentioned side effects or other problems. American Diabetes Association (ADA) Guidelines suggest reducing LDL to 30% to 40% regardless of the baseline, which can be quite challenging.
What do you do when the patient says, "I don't want to be on any more drugs?"
Patients must be counseled on the risks and benefits of using statins or a combination drug therapy so they can make an informed treatment decision. For example, are patients concerned because they do not want to take the drug or are they really concerned about its cost? Perhaps some generic formulations can be considered.
If patients are concerned with the number of pills they are taking, there are many combination pills available as options. Sometimes combination pills are more expensive, but exploring these options may be helpful. Above all, it is first important to understand the reasons behind the patient's apprehension.
Beyond lowering blood pressure, what else should physicians do to lower the risk for CVD in patients with type 2 diabetes?
Physicians can encourage patients with type 2 diabetes to lower their risk for CVD in the following ways:
- HDL and triglyceride control. These remain secondary treatment priorities (except for instances of severely elevated triglycerides). Low HDL cholesterol levels (<40 mg/dL in men and <50 mg/dL in women) are also clearly associated with increased CV risk; however, fewer treatment options are available (eg, lifestyle changes and extended-release niacin), although statins and fibrates also lead to a modest increase in HDL cholesterol level. Low levels of HDL cholesterol are also commonly associated with increased triglyceride levels, which is accounted for by increased very low-density lipoprotein particles. The evidence for reducing CV risk by lowering triglyceride levels, however, is less compelling than for lowering LDL levels.
- Smoking cessation.
- Aspirin therapy. This treatment is still indicated for secondary risk prevention and is supported by strong evidence. However, there is less evidence for use of aspirin therapy as primary prevention. Formal consensus guidelines from the ADA, American Heart Association and American College of Cardiology are expected this year. The ADA recently relaxed its recommendations for aspirin therapy in individuals at increased CV risk (10-year risk >10%, generally men older than 50 years, women older than 60 years with one or more major risk factors) and in individuals who are not at increased risk for bleeding.
- Glycemic control. Glycemic control is achieved initially through therapeutic lifestyle changes (including medical nutrition therapy and exercise), but importantly, medication should not be delayed in order to implement these changes. Initial therapy probably should include metformin if not contraindicated. However, combination oral and non-insulin-injectable glucose-lowering therapy is required in most patients. Patients with very poor control (HbA1c >10%) who are significantly symptomatic (eg, weight loss, fatigue) or who do not meet glycemic targets when using other agents should receive insulin therapy. The most significant mistake that providers make is delaying the start of insulin therapy in patients who need it.
- For most patients, a target HbA1c of 7% is appropriate. In patients with recent diagnosis of type 2 diabetes, no comorbidities and no risk for adverse events, tight glycemic control (aiming for normoglycemia or HbA1c target <6.5%) may reduce CV events where it can be achieved safely and easily, particularly over the long term. In some patients, attainment of glycemic control is neutral for CV benefit and, in some instances, in patients with more advanced disease may be harmful. There are no data regarding treatment strategies or preference for one agent over another.
The bottom line is that multiple risk factor management must be the focus for preventing CV events. This was recently supported by the STENO-2 study, which showed that multifactorial intervention, including glucose, lipid, and blood pressure regulation using multiple drug therapy, reduced the risk for nonfatal CVD as well as microvascular complications, such as neuropathy, nephropathy and retinopathy, among patients with type 2 diabetes.
Do you think that multiple risk factor management is important to implement when treating patients with type 2 diabetes?
Multiple risk factor management is imperative, although it can be an overwhelming concept. Many patients have multiple risk factors. Many of these risk factors require lifestyle interventions, and many patients do not have the resources (eg, insurance coverage) that would allow them to obtain adequate diabetes education. Multiple risk factor management aimed at tightly controlling blood glucose, blood pressure and lipids can open a new set of difficulties in terms of patient compliance with medications.
For more information:
- Laakso M. Diabetes Care. 2010;33(2):442-449.
- Gaede P. The New England Journal of Medicine. 2008;358(6):580-591.