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Diabetes Distilled: Risk factor control and cardiovascular event risk in people with type 2 diabetes in primary and secondary prevention settings

Kevin Fernando
This high-quality observational study suggests that there is still clinically significant residual cardiovascular risk in people living with type 2 diabetes, even when cardiovascular risk factors are optimally managed. Over 6 years of follow-up in Scotland, cardiovascular events occurred in 31% of people with type 2 diabetes, while UK-wide data over 3 years of follow-up revealed cardiovascular events in 27% of people with type 2 diabetes versus 19% of matched controls without the condition. Compared to controls, people with type 2 diabetes and optimal cardiovascular risk factor control still had a 21% higher risk of CVD events. Surprisingly, in those with type 2 diabetes but without cardiovascular and/or renal disease, there was a stronger association between the degree of risk factor control and the subsequent risk of cardiovascular events and mortality compared to those with type 2 diabetes and comorbid cardiorenal disease. These findings have significant implications for all working in primary care and suggest that early and more intensive intervention is required in those living with type 2 diabetes who are deemed to be at lower risk; that is, those without established cardiorenal disease.

Around one third of people living with type 2 diabetes also have cardiovascular disease (CVD). Moreover, CVD can occur 10–15 years earlier in people with diabetes compared to those without diabetes, and a diagnosis of diabetes accelerates the time to the first cardiovascular event. CVD is responsible for approximately half of all deaths in people living with type 2 diabetes, with many of these deaths premature (McMurray et al, 2014; Einarson et al, 2018).

The seminal Steno-2 trial (Gaede et al, 2008) demonstrated that an intensive multifactorial approach to treating cardiovascular risk factors in people living with type 2 diabetes might halve the risk of CVD events and mortality, and may extend life expectancy by up to 8 years. However, even when CVD risk factors are optimally controlled, there is still significant residual cardiovascular risk in people with type 2 diabetes. The TNT (Treating to New Targets) study demonstrated that aggressive lipid-lowering therapy with atorvastatin 80 mg in people with type 2 diabetes resulted in an impressive 25% relative risk reduction in major cardiovascular events; however, 14–18% of individuals still experienced an event regardless of therapy (Shepherd et al, 2006).

There remains uncertainty in the UK whether people with type 2 diabetes and optimally controlled cardiovascular risk factors have similar risks of CVD and mortality to people without diabetes. Quantifying these risks is important to facilitate appropriate interventions (both pharmacological and non-pharmacological) for cardiovascular risk factors.

This large, well-conducted, retrospective cohort study examined the association between the degree of risk factor control and risk of CVD in people living with type 2 diabetes. Additionally, it explored whether any association was modified by baseline cardiovascular risk. Over 130 000 individuals with type 2 diabetes were identified and matched by age, sex, general practice and index date to controls without diabetes.

The study was based in part on CPRD (Clinical Practice Research Datalink) and SCI-Diabetes data. CPRD collects anonymised patient data from a network of GP practices across the UK. Primary care data are linked to a range of other health-related data to provide a longitudinal, representative UK population health data set. The data encompass 50 million patients, including 16 million currently registered patients. SCI-Diabetes was commissioned and is owned by the Scottish Government. It provides a fully integrated, shared electronic patient record to support treatment of NHS Scotland patients living with diabetes.

The authors found that, in CPRD, the mean baseline age in those with type 2 diabetes was 63 years and 28% had cardiovascular and/or renal disease, while in SCI-Diabetes the mean age was 62 years and 35% had cardiorenal disease. Over 3 years of follow-up in CPRD, CVD events occurred in 27% of people with type 2 diabetes and 19% of matched controls. Over 6 years of follow-up in SCI-Diabetes, CVD events occurred in 31% of people with type 2 diabetes. Overall, only 6% of people with type 2 diabetes had optimal risk factor control.

In CPRD, compared to controls without diabetes, those with type 2 diabetes and optimal cardiovascular risk factor control still had a 21% higher risk of CVD events. There was also a 31% higher risk of hospitalisation for heart failure.

Overall, in those with type 2 diabetes but without cardiorenal disease, there was a stronger association between the degree of risk factor control and the subsequent risk of CVD events and mortality compared to those with type 2 diabetes and cardiorenal disease at baseline. Those individuals without cardiorenal disease at baseline tended to be younger (mean age, 59 years) and, predictably, were prescribed fewer CVD prevention medications.

This high-quality observational study suggests that there is still clinically significant residual cardiovascular risk in people living with type 2 diabetes, even when cardiovascular risk factors are optimally managed. Furthermore, this appears to be the first published evidence to suggest that the association between cardiovascular risk factors and CVD outcomes is stronger in lower-risk individuals without cardiorenal disease than in higher-risk individuals with cardiorenal disease.

These findings have significant implications for all working in primary care and suggest that early and more intensive intervention is required in those living with type 2 diabetes who are deemed to be at lower risk; that is, those without established cardiorenal disease. This can be facilitated with guideline-driven care and clinical decision support to increase awareness and confidence in using newer agents such as SGLT2 inhibitors and GLP-1 receptor agonists with proven cardiorenal benefits beyond their glucose-lowering effects.

Click here to read the study in full.

REFERENCES:

Einarson TR, Acs A, Ludwig C, Panton UH (2018) Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovasc Diabetol 17: 83
 
Gaede P, Lund-Andersen H, Parving HH, Pedersen O (2008) Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 358: 580–91
 
McMurray JJ, Gerstein HC, Holman RR, Pfeffer MA (2014) Heart failure: a cardiovascular outcome in diabetes that can no longer be ignored. Lancet Diabetes Endocrinol 2: 843–51
 
Shepherd J, Barter P, Carmena R et al (2006) Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study. Diabetes Care 29: 1220–6

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