Cardiovascular risk
Patients with diabetes mellitus (DM) have a significantly increased risk of
developing cardiovascular diseases with their sequelae of acute myocardial
infarction, stroke and cardiovascular death. For example, even today a 60-year-old
male patient with diabetes has 6 years less life expectancy compared to a
metabolically healthy male of the same age, and a 60-year-old patient with diabetes
and a previous history of a heart attack has 12 years less [1]. These data highlight the need for targeted
risk stratification of patients with diabetes and the consistent treatment of
diabetes, associated risk factors and cardiovascular disease.
Patients with diabetes mellitus should be categorized according to their
cardiovascular risk into those with very high cardiovascular risk, high
cardiovascular risk and moderate cardiovascular risk [2].
Very high cardiovascular risk
DM and existing cardiovascular disease, or end organ damage, or≥3 risk
factors or diabetes duration>20 years.
High cardiovascular risk
DM with a diabetes duration>10 years without end organ damage, but with
an additional risk factor.
Moderate cardiovascular risk
Young patients (type 1 diabetes<35 years; type 2 diabetes<50
years) with a diabetes duration<10 years without other risk factors.
Further risk stratification
In addition to diagnostics for the above-mentioned risk stratification, patients
with diabetes and hypertension or clinical suspicion of cardiovascular disease
should receive a resting ECG. At present, no convincing data exist to use
additional imaging techniques such as echocardiography, stress echocardiography,
scintigraphy or MRI in asymptomatic patients with diabetes mellitus. As part of
clinical routines, no determination of circulating biomarkers should be carried
out as part of risk stratification.
Cardiovascular risk reduction
Cardiovascular risk reduction
For the recommendations on the reduction of cardiovascular risk in diabetes
treatment, refer to the DDG practice recommendations on the therapy of type 2
diabetes (see p. 65–92) and on the treatment of lipid metabolic disorders
(see p. 160–165). Therefore, only the basic statements are listed here:
-
Patients with diabetes should receive structured advice on how to stop
smoking. For patients with diabetes, a Mediterranean diet enriched with
polyunsaturated and monounsaturated fatty acids is recommended. Patients
with diabetes should perform moderate to strenuous physical activity for at
least 150 min/week.
-
In patients with type 2 diabetes and very high cardiovascular risk, a target
value for LDL cholesterol of<55 mg/dL and a minimum
of 50% reduction in LDL cholesterol is recommended. For patients
with a high cardiovascular risk, a target value of 70 mg/dL
and a minimum of 50% reduction in LDL cholesterol is recommended.
For patients with a moderate risk, a reduction in LDL cholesterol
to<100 mg/dL is recommended.
-
The administration of aspirin (100 mg/day) is recommended for
secondary prevention in patients with diabetes mellitus. In the context of
primary prevention, patients with diabetes should not receive antiplatelet
therapy. Platelet aggregation inhibition after acute coronary syndrome
and/or coronary intervention (duration of dual antiplatelet therapy,
etc.) should be coordinated with the treating cardiologist.
-
In accordance with the new guideline of the European Society of Cardiology,
patients with diabetes mellitus should have a target systolic blood pressure
of 130 mmHg. If possible, systolic values<130 mmHg
should be targeted. The diastolic blood pressure target
is<80 mmHg. A blood pressure
setting<120/70 mmHg should be avoided.
-
When adjusting blood glucose levels, patients without a cardiovascular
pre-existing condition should be treated according to the recommendations
for type 2 diabetes; in patients with a pre-existing cardiovascular
condition, hypoglycaemia should be avoided and proven therapy strategies in
reducing cardiovascular risk should be used. Therefore, GLP-1 receptor
agonists and/or SGLT-2 inhibitors with proven event reduction should
be used for reducing cardiovascular events and mortality based on the
results of large cardiovascular endpoint studies in cases of type 2 diabetes
and cardiovascular diseases or a high/very high cardiovascular
risk.
Diabetes and coronary heart disease
Diabetes and coronary heart disease
All patients with coronary heart disease should be examined for the presence of
diabetes mellitus (see Diagnostics and Classification of Diabetes Mellitus). For
prognostic factors, patients with diabetes mellitus and coronary heart disease
should receive platelet aggregation inhibitors, ACE inhibitor therapy and
lipid-lowering therapy with statins.
The first year after myocardial infarction the administration of a beta-blocker
additionally leads to an improvement of the prognosis, whereby this effect decreases
over the course of time. With respect to antidiabetic therapy, for patients with
type 2 diabetes at high cardiovascular risk, empagliflozin [3] or canagliflozin [4] versus placebo. In addition, empagliflozin
significantly reduced all-cause mortality [3}. In DECLARE, there was no significant
effect for dapagliflozin vs. placebo [5].
However, it seems that the individual substance is less important for the different
results in the studies than the patient population. Similarly, in LEADER with
liraglutide [6], in SUSTAIN-6 semaglutide [7], in HARMONY with albiglutide [8], in REWIND with dulaglutide [9], and in PIONEER-6 [10] with oral semaglutide vs. placebo showed a
significant reduction in the 3-point MACE endpoint. In addition, liraglutide and
oral semaglutide vs. placebo reduced all-cause mortality in the LEADER trial and
PIONEER 6 trial, respectively. Administration of semaglutide resulted in significant
reduction of cardiovascular events [11].
Against the background of these data, therapy with one of these substances should be
an integral part of blood glucose-lowering therapy in patients with diabetes and
cardiovascular disease.
In the presence of coronary artery disease requiring intervention or surgery, the
therapy of coronary revascularization in patients with diabetes does not differ from
the therapy in patients without diabetes. In complex coronary findings with
multi-vascular disease and low perioperative mortality, bypass surgery appears to be
superior to coronary intervention. The decision on the revascularization procedure
to be performed (coronary intervention or bypass surgery) should always be made by
the interdisciplinary cardiac team in the case of complex coronary heart
disease.
Diabetes and heart failure
Diabetes and heart failure
Epidemiological and clinical data of recent years have shown that patients with
diabetes mellitus have a significantly increased risk of developing heart failure
and that the prognosis of patients with diabetes and heart failure is significantly
worse than that of patients with heart failure without diabetes [12], [13].
Heart failure with a reduced ejection fraction (HFrEF), Heart failure with preserved
ejection fraction (HFpEF) and Heart failure with mildly reduced ejection fraction
(HFmrEF) are categorized according to the recommendation of the European Society of
Cardiology guideline ([Tab. 1]) [14]. In principle, it can be said that half of
patients with heart failure and diabetes have impaired left ventricular
function.
Tab. 1 Definition of heart failure with preserved (HFpEF),
moderately restricted (HFmrEF) and reduced ejection fraction
(HFrEF).
|
HF type
|
|
HFrEF
|
HFmrEF
|
HFpEF
|
|
Criteria
|
1
|
Symptoms±sign1
|
Symptoms±sign1
|
Symptoms±sign1
|
|
2
|
LVEF<40%
|
LVEF 40-49%
|
LVEF≥50%
|
|
3
|
–
|
1. Increased serum concentrations of natriuretic
peptides22. At least 1 additional criterion:a.
Relevant structural heart disease (LVH and/or LAE)b.
Diastolic dysfunction3
|
1. Increased serum concentrations of natriuretic
peptides22. At least 1 additional criterion:
|
LAE Left atrial enlargement (left atrial volume index
[LAVI]>34 ml/m2 ); LVH left
ventricular hypertrophy (left ventricular muscle mass index
[LVMI]≥115 g/m2 for men
and≥95 g/m2 for women).; 1
Signs may be absent in early stages of heart failure (especially HFpEF) and
in patients on diuretic treatment. 2
BNP>35 pg/ml and/or
NT-proBNP>125 pg/ml. 3 E/A
ratio≥13, mean (septal and lateral) "E"
velocity<9 cm/s (for details see section 4.3.2 in
[1] ). LAE = Left atrial
enlargement, LVEF = left ventricular ejection fraction, LVH
= Left ventricular hypertrophy.
At present, clinical data only exist for patients with HFrEF that suggest an
improvement in prognosis. The therapy for HFrEF in patients with diabetes does not
differ from the therapy of non-diabetic patients in terms of both drug therapy and
device therapy (Implantable cardioverter defibrillator [ICD], Cardiac
Resynchronization Therapy [CRT]). For HFpEF and HFmrEF there are no data available
that reliably prove an improvement in the prognosis of the patients, so that
symptomatic therapy options -e. g. the administration of diuretics –
and a treatment of comorbidity -e. g. adjustment of the arterial
hypertension – are in the foreground.
With regard to blood glucose-lowering therapy, the studies with empagliflozin,
canagliflozin, dapagliflozin, and ertugliflozin showed a significant reduction in
hospitalization for heart failure, so that these substances should be used in
patients at high risk for heart failure and in patients with heart failure for blood
glucose lowering and reduction of cardiovascular morbidity and mortality. For
patients with HFrEF, the DAPA-HF and EMPEROR-Reduced trials are also available, both
conducted in patients with and without diabetes. Administration of dapagliflozin or
empagliflozin significantly reduced worsening heart failure, cardiovascular death,
or all-cause mortality regardless of the presence of diabetes mellitus [15], [17].
Dapagliflozin is the first SGLT-2 inhibitor since the end of 2020 to be approved for
the treatment of heart failure with an ejection fraction<40%
(HFrEF), regardless of the presence of diabetes mellitus. Important to note in this
regard is the Estimated Glomerular Filtration Rate (eGFR) limit, which is important
for use. While dapagliflozin may be started at an
eGFR>60 ml/min and continued up to an eGFR of
45 ml/min for the treatment of diabetes mellitus, therapy may be
started and continued in patients with heart failure up to an eGFR of
30 ml/min. In addition, on May 20, 2021, the Committee for Medicinal
Products for Human Use (CHMP) gave a positive evaluation to empagliflozin for the
treatment of heart failure with reduced ejection fraction. European approval was
granted on June 21, 2021, making two SGLT-2 inhibitors currently available for the
treatment of heart failure with reduced ejection fraction. Due to the increased risk
of hospitalization for heart failure, glitazones and the DPP4 inhibitor saxagliptin
are contraindicated in patients with heart failure.
Diabetes and atrial fibrillation
Diabetes and atrial fibrillation
The presence of diabetes mellitus is a separate risk factor for thromboembolic events
in patients with atrial fibrillation. All patients with atrial fibrillation should
be risk stratified for their risk of thromboembolism using the CHADS-VASC score
([Tab. 2]) and accordingly receive
anticoagulation with vitamin K antagonists and Non-vitamin K antagonist oral
anticoagulants (NOACs) [16]. At this stage, no
data exists that show a prognostic advantage of a rhythm restoration (cardioversion
in the sinus rhythm) or frequency control in atrial fibrillation. In this respect,
the procedure is comparable for patients with and without diabetes.
Tab. 2 Approach based on risk factors, expressed as point
system with the acronym CHA2DS2 -VASc
score.
|
Risk factor
|
Score
|
|
Chronic heart failure or left ventricular dysfunction
|
1
|
|
Hypertension
|
1
|
|
Age≥75 years
|
2
|
|
Diabetes mellitus
|
1
|
|
Stroke/TIA/thromboembolism
|
2
|
|
Vascular disease history1
|
1
|
|
Age 65-74 years
|
1
|
|
Female
|
1
|
|
Maximum score
|
9
|
Note: As the age can be evaluated with 0, 1 or 2 points, the maximum score is
9. 1 Condition after myocardial infarction, peripheral arterial
occlusive disease, or plaque in the aorta. TIA = Transient ischemic
attack.
German Diabetes Association: Clinical Practice Guidelines
This is a translation of the DDG clinical practice guideline
published in Diabetologie 2021; 16 (Suppl 2): S319–S323
DOI 10.1055/a-1515-9121
