The 2019 guideline developed in collaboration with the European Association for the Study of Diabetes (EASD) comes as the third update and elaborates the means to manage and prevent Cardiovascular Diseases (CVD), a risk associated to pre-diabetes and Diabetes Mellitus (DM) patients.

This concise version highlights the updates, changes or additions in the 2019 version and many important recommendations for different glucose metabolism-related disorders. It provides information for management and prevention of CVD in diabetics and pre-diabetics, based on the current state-of-the-art treatments.

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Why was the guideline updated?

The guideline emphasises on a prediction that more than 600 million individuals around the world would be victims of Type 2 Diabetes Mellitus (T2DM) by the year 2045 and possibly a similar number of people would develop pre-DM. Hence, it became important to create awareness about its effects on the heart and vasculature, which varies in different races and sex and even with increasing age.

The prediction and the possible comorbidities make it essential to ensure that different methods of management and prevention of associated CV risks are known and the patient is abreast with information that can make him or her capable of managing his/her condition better.

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Key messages of the guideline

1. CV risk assessment in DM and pre-DM: Classification of CV risk (moderate-to-very high risk) adapted from the 2016 ESC Guidelines on CVD prevention in clinical practice to the DM setting.
2. Lifestyle:

• Moderate alcohol intake should not be promoted as a means to protect against CVD
• Obese DM patients need to target a weight loss of >5% to enjoy an overall improvement in health
• Vitamins or micronutrients are not recommended for lowering CVD risks. Less protein is recommended for DM patients with CKD
• For patients with pre-DM and DM, weekly two sessions of resistance exercise and engaging in regular moderate physical activity for pregnant women with DM is recommended

3. BP control: Detailed recommendations for individualized BP targets are now provided
4. Glucose-lowering treatment (a paradigm shift after recent CVOTs): For the first time, many Cardiovascular Outcome Trials (CVOTs) conclude that DM patients can get help in CV treatment by using glucose-lowering medicines for high to very high CV risk. The results that were based on both, GLP1-RAs (LEADER, SUSTAIN-6, Harmony Outcomes, REWIND, and PIONEER 6) and SGLT2 inhibitors (EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58, and CREDENCE), and they indicate that these drugs should be recommended for T2DM patients with an existing CVD or very high/high CV risk. These can be used on patients who are treatment-naïve or already on metformin.

   GLP1-RAs help by minimising arteriosclerosis-related events and SGLT2 inhibitors help bring down HF-related endpoints, benefitting those who run a high HF risk.

   As per UKPDS’s (UK Prospective Diabetes Study) observation made in clinical practice, Metformin helps in primary prevention in newly diagnosed T2DM without CVD and running a moderate risk.

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Diagnosing Diabetes and Pre-Diabetes

ESC recommends diagnosing DM based on HbA1c or FPG, and on OGTT to clarify doubts. OGTT is essential to diagnose impaired glucose tolerance (IGT). Tests can also be repeated for confirmation. For CVD patients, the same methods should be applied.

In the Glucose Abnormalities in Patients with Myocardial Infarction (GAMI) study, OGTTs came up with the result; reported that two-thirds of patients without DM had either developed DM or were pre-DM.

The Euro Heart Survey on Diabetes and the Heart and EUROASPIRE IV results showed that an OGTT may help identify a higher number of patients with CVD as having glucose abnormalities than FPG or HbA1c.

1. Patients admitted for coronary angiography too reported similarities. However, in patients of acute coronary syndromes (ACS), OGTT should not be performed before 4–5 days so as to reduce the chances of false-positive results.
2. Patients with CVD should first be screened using HbA1c and/or fasting glucose test. OGTT can be used if the FPG and HbA1c turns out to be in doubt.

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Cardiovascular risk assessment in pre-diabetes and diabetes patients

1. Routine assessment of microalbuminuria is advised to identify patients, who may develop renal dysfunction and/or CVD
2. A resting ECG for patients with DM and hypertension or if CVD is suspected.
3. Transthoracic echocardiography, coronary artery calcium (CAC) score, ankle–brachial index (ABI) and other tests may be conducted to diagnose structural heart diseases or identify risk modifiers in patients at a moderate or high risk of CVD.
4. As for CV risk stratification, routine assessment of novel biomarkers is not recommended.

Other conclusions drawn from The Emerging Risk Factor Collaboration, which was a meta-analysis of 102 prospective studies, were:

1. DM in general (DM type unspecified) means a two-fold higher risk of vascular outcomes such as, coronary heart disease, ischaemic stroke, and vascular deaths, all exclusive of other risk factors (given below).
2. The chances of ‘higher’ relative risk of vascular problems were greater in women with DM and at younger ages.
3. Risk levels (both relative and absolute) will be higher in patients with long-standing DM and microvascular complications. Emphasising on DM here, the notes can be considered for both types of DM unless otherwise specified.

Recommendations for lowering glucose in diabetes patients

• Metformin can be considered in overweight T2DM patients who may be at moderate risk of a CV event.
• SGLT2 inhibitors- Empagliflozin, canagliflozin and dapagliflozin and GLP1RAs- liraglutide, semglutide and dulaglutide are recommended to reduce CV events in DM patients with CVD or those running a very high/high CV risk.
• Insulin is recommended in ACS (acute coronary syndrome) patients with hyperglycaemia (>10 mmol/L or >180 mg/dL).

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Recommendations for glucose control to lower related CV risks

1. Stringent glucose control initiated early on in younger DM patients can reduce CV outcomes over a 20-year timescale. Less rigorous targets should be considered for elderly DM patients, as per individual requirements, keeping in mind advanced CVD or comorbidities.
2. Post-prandial glucose testing is recommended for patients with on target pre-meal glucose values but above target HbA1c. Management of glucose variability may become an additional goal. Prevention of hypoglycaemia is of critical importance, especially to lower the risk of arrhythmias and myocardial ischaemia (MI).

In T2DM patients, an HbA1c reduction of ∼1% can mean a 15% relative risk reduction in non-fatal MIs, without beneficial effects on stroke, CV, or all-cause mortality or hospitalization for HF. This is reported by a meta-analysis of three major studies—Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), and the Veterans Affairs Diabetes Trial (VADT).

Indications from the meta-analysis:

• Intensive glucose control was beneficial for CV events in patients with a short duration of DM, lower HbA1c at baseline, and no CVD
• HbA1c targets should be individualized, with more-stringent goals [6.0–6.5% (42–48 mmol/mol)] in younger patients with a short duration of DM and no evidence of CVD, if achieved without significant hypoglycaemia
• Less-stringent HbA1c goals [e.g. <8% (64 mmol/mol) or ≤9% (75 mmol/mol)] may be adequate for elderly patients with long-standing DM and limited life expectancy, and frailty with multiple comorbidities, including hypoglycaemic episodes

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Recommendations for BP management in pre-diabetes and diabetes patients

Blood pressure goals:

1. Treatment with antihypertensives is recommended for office reading of >140/90 mmHg.
2. Target SBP goal for hypertensive patients with DM should be 130 mmHg or less, but not less that 120 mmHg, and for patients at high risk of CVD or a history of stroke, SBP target of less than 130 mmHg. In patients above 65 years of age, SGP target should be between 130 to 139 mmHg.
3. DBP target should be 80 mmHg, but not less than 70 mmHg.

Treatment:

1. RAAS (renin-angiotensin-aldosterone system) blockers such as ACEI (angiotensin-converting enzyme inhibitor) or ARB (angiotensin receptor blocker) may be considered for hypertensive DM patients especially those with microalbuminuria, albuminuria, proteinuria, or LV hypertrophy. However, ACEI and ARB combinations are not recommended.
2. RAAS blockers can be used in combination with CCB (calcium channel blockers) or thiazide/thiazide-like diuretic.
3. For patients with impaired fasting glycaemia or impaired glucose tolerance, RAAS should be considered over beta-blockers.

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To access the original guideline document, click here.