Referat - DM Dan Kardiovaskular

Diabetes and Cardiovascular System
Outline
01 Introduction
02 Criteria Diagnostic
03 Risk Stratification
04 Clinical Assessment
05 Prevention
Introduction
• The prevalence of DM worldwide continues to increase

• Rising to 10% of the population in countries
• The prediction >600 million individuals develop T2DM worldwide by 2045
• Guideline provide how to prevent and manage the effects of DM on the heart and vascular
Scope of the Problem
• Diabetes mellitus involves
insufficient production of insulin,
failure to respond appropriately to
insulin, or both, resulting in
hyperglycemia
• Diabetes affect 285 million adults
in 2010  estimated to be 430
million in 2030
Bonow RO, Mann DL, Zipes DP, Libby P. Braunwald's heart disease e-book: a textbook of cardiovascular medicine. Elsevier Health Sciences; 2011 Feb 25.
IFG : Impaired fasting glucose
IGT : impaired glucose tolerance
Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV. 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force for
diabetes, pre-diabetes, and cardiovascular diseases of the European Society of cardiology (ESC) and the European association for the study of diabetes (EASD). European heart journal. 2020 Jan 7;41(2):255-323.
• Atherosclerotic disease + diabetes 2-3x risk
• Heart failure + diabetes 2-5x risk
• Atrial fibrillation + diabetes augmenting stroke risk
Bonow RO, Mann DL, Zipes DP, Libby P. Braunwald's heart disease e-book: a textbook of cardiovascular medicine. Elsevier Health Sciences; 2011 Feb 25.
Stratification of Cardiovasular Risk
DM PRE-DM
• Individuals without CVD who
have pre-DM are not
necessarily at elevated CV
risk, but warrant risk scoring
for CVD in the same way as
the general population
Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV. 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force for diabetes, pre-
diabetes, and cardiovascular diseases of the European Society of cardiology (ESC) and the European association for the study of diabetes (EASD). European heart journal. 2020 Jan 7;41(2):255-323.
Clinical Assessment of Cardiovascular Damage
Biomarkers
• hsTnT, NT-pro BNP, Albuminuria
ECG
• Silent MI, QTc Interval, Heart Rate
• Exercise ECG :
• 20-40% detecting silent ST segment depression
• Detecting silent CAD : sensitivity 47% ; specificity 81%
Imaging
• Echocardiography, CT, Carotid Intima thickness
Cardiovascular Prevention in DM
LIFE GLYCEMIC
STYLE TARGET
BLOOD LIPID
PRESSURE
PLATELET
Life Style
• Diet
• Physical Exercise
• Smoking Cessation
Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV. 2019 ESC guidelines on
diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force for diabetes, pre-diabetes, and cardiovascular
diseases of the European Society of cardiology (ESC) and the European association for the study of diabetes (EASD). European heart journal. 2020 Jan
7;41(2):255-323.
Glycemic Control
• HbA1c < 7
• Avoid Hypoglycemia
• Glucose monitoring
Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV. 2019
ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force for
diabetes, pre-diabetes, and cardiovascular diseases of the European Society of cardiology (ESC) and the European association for the
study of diabetes (EASD). European heart journal. 2020 Jan 7;41(2):255-323.
Blood pressure
Target SBP < 130, not less than 120 for SBP; and < 80 for DBP
In elderly, target SBP 130-140
RAAs blocker  recommended in DM with albuminuria, proteinuria, or LVH
Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV. 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases
developed in collaboration with the EASD: the task force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of cardiology (ESC) and the European association for the study of diabetes
(EASD). European heart journal. 2020 Jan 7;41(2):255-323.
Statin therapy has been associated with new-onset DM : for every 40 mmol/L(mg/dL) reduction of
LDL-C by statins, conversion to DM is increased by 10%
Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, Braunwald E, Kastelein JJ, de Lemos JA, Blazing MA, Pedersen
TR, Tikkanen MJ, Sattar N, Ray KK. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a metaanalysis. JAMA 2011;305:2556-2564
Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV. 2019 ESC guidelines on diabetes, pre-diabetes,
and cardiovascular diseases developed in collaboration with the EASD: the task force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of cardiology
(ESC) and the European association for the study of diabetes (EASD). European heart journal. 2020 Jan 7;41(2):255-323.
Platelet
ASCEND Trial
15480 patients with DM with no
CVD to 100 mg aspirin/day
Primary outcome 8,5% : 9,6%
Bleeding 4,1% : 3,2%
¼ patients got PPI at the end of
study
Management CAD with DM
Medical Therapy
High/very high risk :
SGLT 2 inhibitor and GLP 1 RA monotherapy
Glycemic control
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Specific Cardivascular medication

Revascularization
Recommendations for Glucose-lowering
Treatment in DM
Recommendations for Glucose-lowering
Treatment in DM
SGLT-2 Inhibitors
Canagliflozin, dapagliflozin, empagliflozin
Inhibiting SGLT-2 in the Meal Intestine

proximal convoluted tubule: glucose
• increases glucosuria absorption
• inhibits renal glucose SGLT-1
reabsorption
• causes weight loss Blood

• does not induce hypoglycemia glucose
• reduces blood pressure
• gives CV benefits Inhibition of kidney
• may have renal benefits glucose re-absorption
by 20-30%
X
SGLT-2
SGLT-1
Glucosuria
SGLT-2 inhibitors; sodium-glucose cotransporter-2 inhibitors
70-90 g/day
Bailey CJ, Day C. Br J Diabetes Vasc Dis 2010; 10: 193-9.

Summary of CVOTs with GLP-1R Agonists
Main Primary Secondary Follow-up

Intervention N
Inclusion Criteria Outcome Outcome Period
Lixisenatide ACS event ≤180 days prior to 2.1 years
ELIXA1 6068 4P-MACE Expanded MACE
Placebo screening median
REPORTED
Established CVD (≥50 years),

Liraglutide 3.8 years
LEADER 2
or ≥60 years + ≥1 CV risk 9340 3P-MACE Expanded MACE
Placebo median
factor
Semaglutide Established CVD, HF or CKD
SUSTAIN- 2.1 years
* stage ≥3 (≥50 years), or 3297 3P-MACE Expanded MACE
63 median
Placebo ≥60 years + ≥1 CV risk factor
Exenatide All-cause mortality;
Any level of CV risk, including 3.2 years
EXSCEL 4
ER* 14,752 3P-MACE HHF, hospitalization
prior CV event median
Placebo for ACS
Exenatide Coronary, cerebrovascular or
†
~4000 4P-MACE Not specified ~5 years
FREEDOM 5
Placebo peripheral artery disease
Dulaglutide Pre-existing vascular disease All-cause mortality, Up to
REWIND6 ~9622 3P-MACE
Placebo or ≥2 CV risk factors HHF, HUA 6.5 years
Albiglutide Expanded MACE,
HARMONY- Established CVD ~9400 3P-MACE 3–5 years
Placebo HHF
Outcomes7
*, once weekly; †, via DUROS device;
Pfeffer MA et al. N Engl J Med. 2015;373:2247-57; Marso SP et al. N Engl J Med. 2016;375:311-22; Marso SP et al. N Engl J Med.
2016;375:1834-1844
Specific CV Agent
PCI VS CABG
Heart failure and Diabetes
• Reducing risk of HF
• Pharmacotherapy
• Click to edit Master text styles
• Second level
• Third level
• Fourth level
• Fifth level
Arrhythmias and dm
• Atrial Fibrillation
• Ventricular Arrhythmias and Sudden Death
• DM  Independent risk factor for AF
• DM increase chance of acute Hf in the
setting of new onset – AF
• AF + DM  ↑ All cause death, CV
death, stroke and HF
• DM increases the risk of stroke in
paroxysmal or permanent AF
• Current Guidelines recommend that oral
anti coagulant therapy, with NOACs or
VKAs, should be considered
• Kidney function should be carefully
evaluated in patients with DM when
prescribing a NOAC to avoid over-dosage
Ventricular arrhythmia
and sudden death
• CHARM study  DM predictor of mortality

• The causes underlying increased vulnerability
to electrical instability in DM are unclear 
several factor  Nephropathy, autonomic
neuropathy, prolonged QTc interval,
hypoglycemia, and comorbidities related to DM
• Diagnostic workup does not differ between DM
and non-DM
• In highly symptomatic patients with PVC or
NSVT, medication or catheter ablation can be
used to suppress arrhythmias
• Most patients with sustained VT or aborted
cardiac arrest without a diagnosed trigger need
an ICD to prevent sudden death
Aorta, Pad AND DM
• Aortic disease
• LEAD
• Carotid Artery Disease
• Aortic Disease
• DM shows decrease incidence of Abdominal Aorta Aneurysm  But the outcome
in AAA repair is poorer in DM
• No specific recommendation  Lack of study
• Recommendation is the same with general population
• Carotid Artery Disease
• 10-15% stroke from thromboembolism in carotid artery
• COMPASS Trial
• 27.395 patients with stable CAD :
• rivaroxaban 2.5 mg b.i.d. plus aspirin 100 mg o.d VS rivaroxaban5mg b.i.d. or aspirin 100 mg o.d.
• Sub study of 7240 patients with CAD or LEAD with a mean follow-up of 23 months (44% with DM)  major adverse limb events
including amputation were significantly decreased with combination therapy at the cost of major bleeding risk
• Patients with intermittent claudication should take part in exercise training programmes (> 30-45 min, at
least 3 times/week)  improves walking distance  less pronounced benefits in patients with DM
• CLTI  strict glycamic control is associated with improved limb outcomes
• Revascularization should be attempted when possible and should be considered in severe/disabling
claudication
• Amputation should be considered only when revascularization failed
• No specific trial for revascularization in DM  But a review of 56 studies including patients with DM
suggested higher limb salvage rates after revascularization (78-85% at 1 year )compared with
conservative management
CKD in DM
• Approaching DM in patient with CKD
• Nephroprotection has been observed in GLP1-RA (liraglutide and semaglutide) and three
SGLT2 inhibitor (empagliflozin, canagliflozin, dapagliflozin)  These trials did not include
patients with advanced CKD
• Several studies have been initiated [DAPA-CKD, EMPA-Kidney, and CREDENCE].
• CREDENCE
• Patients with T2DM and eGFR 30 to <90 (urinary albumin : creatinine ratio 33.9-565 mg/mmol) to
canagliflozin100 mg/day or placebo
• A total of 4401 patients were followed for 2.6 years and the relative risk of the primary outcome (a
composite of end-stage renal disease, a doubling of serum creatinine levels, or renal or CV death) was
reduced by 30%
• Secondary outcomes, including the composite of CV death or hospitalization for HF; the composite of CV
death, MI, or stroke; and the analysis of hospitalization for HF alone, all demonstrated significant benefits
with canagliflozin
• This trial also demonstrated that the SGLT2 inhibitor canagliflozin may be used with benefit down to an
eGFR of 30mL/min/1.73m2
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Multiple causes Type 2 Diabetes
Insufficient ↑ glucose
insulin Islet
production
β-cells
Excess
glucagon ↓ glucose uptake
and metabolism
Defective Islet α-cells
Blood
Blood
incretin glucose
effect glucose
Excess adiposity
Altered Pro-inflammatory
microbiome
Autonomic ↑ glucose
disturbances reabsorption
Bailey CJ. Clin Pharmacol Ther 2015;98(2):170-84

Anastasia Poznyak, Andrey V. Grechko, Paolo Poggio. Diabetes Mellitus – Atherosclerosis Connection : the role of lipid and glucose metabolism and chronic inflammation.
International journal of molecular science 2020 March 6.
Guideline 2019

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Diabetes and Cardiovascular System

• The prevalence of DM worldwide continues to increase

Specific Cardivascular medication

Inhibiting SGLT-2 in the Meal Intestine

• causes weight loss Blood

Bailey CJ, Day C. Br J Diabetes Vasc Dis 2010; 10: 193-9.

Main Primary Secondary Follow-up

Established CVD (≥50 years),

*, once weekly; †, via DUROS device;

• CHARM study  DM predictor of mortality

Bailey CJ. Clin Pharmacol Ther 2015;98(2):170-84

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