RIESGO CARDIOVASCULAR EN EL PACIENTE DIABETICO J GONZALEZ JUANATEY

Información Atención Primaria| 2
RIESGO CARDIOVASCULAR EN EL PACIENTE DIABÉTICO
¿Cómo lo Evaluamos?
José R. González-Juanatey
Hospital Clínico Universitario. IDIS, CIBERCV
Santiago de Compostela. España
Conflict of interest:
Research grants and honoraria from (research
committees, clinical trials, personal, Institutional):
Astra-Zeneca, Bayer, Boehringer Ingelheim, Lilly /
Daiichi-Sankyo, Ferrer, MSD, Novartis, Pfizer, Sanofi-
Aventis, Servier, Amgen, Tecnofarma, Silanes

1- Diabetes y
enfermedad CV y Renal

Pathophysiology of CVD in Diabetes
CV, cardiovascular; CVD, cardiovascular disease; MACE, major adverse
cardiovascular events.
Insulin
Resistance
Vasculopenia
Oxidative
Stress
Inflammation
Diabetes
CV Death
Atherosclerotic
(MACE) Events
Heart Failure
Events
Kidney Disease

Cardiovascular-Renal Spectrum of Diabetes
MACE, major adverse cardiovascular events (non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death).
Verma S et al. Lancet. 2019;393:3-5.
Heart
Failure
MACE
Renal
Disease
Diabetes affects the
FILTER
PUMP
PIPES

The Bad Marriage of Diabetes and Chronic Kidney Disease

Cardiorenal disease was most common first comorbidity in T2D
CV = cardiovascular; HF=
heart failure; PAD =
peripheral artery disease;
T2D = type 2 diabetes.
Birkeland KI et al. Poster
presented at: ADA 79th
Scientific Sessions; June 7-11,
2019; San Francisco, CA.
Poster 206-LB.
Time in study, years
Germany Japan Norway Sweden
Patients
with
an
event
(%)
48% cardiorenal disease
CKD = chronic kidney disease; HF = heart failure; MI = myocardial infarction; PAD = peripheral artery disease; T2D = type 2 diabetes.
Birkeland KI et al. Poster presented at: ADA 79th Scientific Sessions; June 7-11, 2019; San Francisco, CA. Poster 206-LB.
Multinational observational cohort study including 645,180 comorbidity-free T2D patients
(mean follow-up of 4.3 years)

Cardiorenal disease was associated with highest mortality
risks in T2D
aAdjusted for age and sex; bDefined as presence of HF and/or CKD; cData only obtainable in Norway and Sweden.
CKD = chronic kidney disease; HF = heart failure; PAD = peripheral artery disease; T2D = type 2 diabetes.
Birkeland KI et al. Poster presented at: ADA 79th Scientific Sessions; June 7-11, 2019; San Francisco, CA. Poster 206-LB.
Multinational observational cohort study including 645,180 comorbidity-free T2D patients
(mean follow-up of 4.3 years)
a
First comorbidity vs. comorbidity-free
c
b
b

2- Evaluación Clínica
Básica del Riesgo CV y
Renal del Diabético

ADA, 2007
DM
100
126
140 200
Impaired
Glucose
tolerance
IFG +
IGT
Impaired
fasting
glycaemia
Normal
2h plasma glucose (mg/dl)
Fasting
plasma
glucose
(mg/dl)
Random plasma glucose
> 200 mg/dl + symptoms
DM
DM
2
3
1
4 HbA1c
> 6,5 %
x 2
x 2
x 1
x 2
ADA
T2DM and Pre-diabetes

ESC 2021 Prevention Guidelines. Risk estimation in T2D
Patients with T2D
Patients with DM with/o ASCVD
and/or severe TOD, and not
fulfilling the mod risk criteria
Patients with DM with ASCVD
and/or severe TOD:
eGFR<45 irrespective of albmin
eGFR 45-49 and microal (30-
300)
Proteinuria (>300)
Presence of microvasc disease
in at least 3 different sites
(microalb, retinopathy,
neuropathy)

EXTREMELY HIGH RISK VERY HIGH RISK HIGH RISK
Adapted from: Robinson JG, et al. Rev Cardiovasc Med 2018;19:S1–8.
CKD, chronic kidney disease; CRP, C-reactive protein; DM, diabetes mellitus; PVD, peripheral vascular disease.
Patient risk groups: ‘risk phenotypes’

Systolic Home Blood Pressure is More Reliable and More Strongly Correlated
with LVH Than Either Office Blood Pressure or Ambulatory Blood Pressure
OFFICE BP HOME BP 24-HOUR BP

Laboratory, ECG and imaging testing for CV Risk assessment
in asymptomatic patients with T2D – ESC 2019 Guidelines

ESC
AF Guidelines
2020

CAROTID PLAQUE FORMATION AND PROGRESSION
VULNERABLE PLAQUE
Rusconi C. 2011

3- Evaluación Clínica Básica del
Riesgo CV y Renal del
Diabético

Etiology of CKD
HTN = hypertensive; IgA = immunoglobulin A; T2D = type 2 diabetes.
Wheeler DC et al. Online ahead of print. Nephrol Dial Transplant. 2020.
58.3%
86.4%
16.0%
6.9%
34.8%
16.1%
3.3%
42.8%
0%
20%
40%
60%
80%
100%
Overall Population (N = 4304) T2D (N = 2906) No Diabetes (N = 1398)
Investigator-Reported
Etiology
of
CKD
(%)
Diabetic Nephropathy Ischemic/HTN Nephropathy Chronic Glomerulonephritis
Chronic Pyleonephritis Chronic Interstital Nephritis Obstructive Nephropathy
Renal Artery Stenosis Unknown Other
Chronic glomerulonephritis
IgA nephropathy (6.3%)
Focal segmental glomerulosclerosis (2.7%)
Membranous nephropathy (1.0%)
Minimal change disease (0.3%)
Other (5.9%)
Other (0.9%)
Other (16.5%)
Ischemic/HTN nephropathy
Diabetic
nephropathy
Diabetic
nephropathy

*Adjusted for age, sex, race or ethnic origin, smoking, SBP, antihypertensive drugs, diabetes, total and high-density lipoprotein cholesterol
concentrations, and albuminuria (UACR or dipstick) or eGFR, as appropriate; #figure adapted from Matsushita K, et al. 2015
CKD, chronic kidney disease; CV, cardiovascular; eGFR, estimated glomerular filtration rate; HF, heart failure; SBP, systolic blood pressure; T2D,
type 2 diabetes; UACR, urine albumin-to-creatinine ratio
1. Matsushita K, et al. Lancet Diabetes Endocrinol 2015;3:514–525; 2. Fox CS, et al. Lancet 2012;380:1662–1673
CV risk increases as eGFR falls below ~75 ml/min/1.73 m2 and UACR exceeds 5 mg/g1
Diabetes further exacerbates this risk2
Patients with CKD and T2D have a high risk of
hospitalisation for HF and CV death
UACR (mg/g)*,2
HF
CV mortality
UACR (mg/g)
0
2.5
0 10
5 30 300 1000
4.0
3.0
2.0
1.5
1.0
0.8
Adjusted
HR
eGFR (ml/min/1.73 m2)*#,2
eGFR (ml/min/1.73 m2)
Adjusted
HR
4.0
3.0
2.0
1.5
1.0
0.8
0
15
0 45
30 75
60 105
90
CV mortality
HF
Reference Reference

Albuminuria categories1
(mg albumin/g creatinine)
A1
Normal to mildly elevated
A2
Moderately elevated
A3
Severely elevated
0–29 30–299 ≥300–4999
GFR
categories
(ml/min/1.73
m
2
)
G1 >90
G2 60–89
G3a 45–59
G3b 30–44
G4 15–29
G5 <15
Kidney Risk estimation in T2D. eGFR and Albuminuria

24
Albuminuria categories1
Description and range
(urine albumin-to-creatinine ratio)
A1
Normal–mildly
increased
A2
Moderately
increased
A3
Severely
increased
<30 mg/g
(<3 mg/mmol)
30–300 mg/g
(3–30 mg/mmol)
>300 mg/g
(>30 mg/mmol)
GFR
stages
description
and
range
(ml/min/1.73
m
2
)
G1 Normal or high ≥90
G2 Mild 60–89
G3a Mild–moderate 45–59
G3b Moderate–severe 30–44
G4 Severe 15–29
G5 Kidney failure <15
eGFR: 44 ml/min/1.73 m2
UACR: 200 mg/g (20 mg/mmol)
Risk and Management
Implications?
HbA1c: 6.0% (42 mmol/mol)
Kidney Risk estimation in T2D. eGFR and Albuminuria

Categoría de FGe
Empeoramiento
Mejoría/estabilización
MACE
Impacto pronóstico de la evolución de la función renal en pacientes con SCACEST
sometidos a intervencionismo coronario percutáneo primario: registro a 10 años
Tasende P, …, Gonzalez-Juanatey JR. Hellenic Journal of Cardiology 2022.

Options to prevent new onset or worsening renal
function are limited – Major Role of SGLT2i
ONTARGET, BEACON demonstrated increased risk of events.
ALTITUDE = Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints; ARB = angiotensin receptor blocker; ACE = angiotensin-converting
enzyme; BEACON = Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus; DRI = direct renin inhibitor;
IDNT = Irbesartan Diabetic Nephropathy Trial; ONTARGET = Ongoing Telmisartan Along and in Combination with Ramipril Global Endpoint Trial;
RENAAL = Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan; SGLT2i = sodium-glucose cotransporter 2 inhibitor; Sun-
MACRO = Sulodexide macro-albuminuria; VA NEPHRON-D = Veterans Affairs Nephropathy in Diabetes.
2001 2008 2011 2012 2013 2018-22
RENAAL1
IDNT1
ONTARGET1
ROAD MAP1
ALTITUDE1
Sun-MACRO1
VA NEPHRON-D1
BEACON1
SGLT2i2-5
Benefit
Neutral/
Harmful
ARB ARB/ACE combo DRI Anti-inflammatory
Glycosaminoglycan

4- Evaluación Clínica
Básica del Riesgo CV y
Renal del Diabético –
Manejo Multifactorial

New treatment paradigm in T2D
GlucoCentric Aproach
(CV) Events Reduction
Approach
Multifactorial Intervention
HbA1c as the central focus

29
Conventional glucose-lowering therapies have shown limited benefit in reducing CV risk2
HbA1c target individualised; generally ~7%
Lifestyle modification, then metformin/SGLT2i/GLP1a
Glucose
Lipid lowering
LDL < 55 / <70 or < 100 mg/dL (1.8 mmol/L); lifestyle, statin, ezetimibe, PCSK9i
Lipids
Target of <130/80 (140–130/90–80) mmHg
ACEi/ARB, BB
Blood pressure
Antiplatelet use
ASA (75–162 mg/day), DAPT
Antithrombotics
Lifestyle Changes
ARB, angiotensin receptor blocker; BB, beta blocker; CV, cardiovascular; DAPT, dual antiplatelet therapy;
GLP1a, glucagon-like peptide 1a; SGLT2i, sodium glucose transport protein 2 inhibitor.
Optimal CV/KIDNEY risk reduction in Diabetic Patients is
achieved through targeting multiple risk factors

ESC 2021
Prevention
Guidelines.
Risk
estimation in
T2D
Patients with Type 2 Diabetes Mellitus

Diabetes
1º paso

Diabetes
2º paso

Cardiovascular-Renal Spectrum of Diabetes
MACE, major adverse cardiovascular events (non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death).
Verma S et al. Lancet. 2019;393:3-5.
Heart
Failure
MACE
Renal
Disease
FILTER
PUMP
PIPES

34
Diabetes Mellitus and Ischemic Heart Disease
Diagnóstico Clínico
No se justifica búsqueda isquemia silente

Stretched and dilated chambers
Stiffened and thickened chambers
Patients with T2D and CAD are at higher risk of left
ventricular heart failure
35
Failure of
normal
relaxation and
filling
Failure of
normal
contraction
and emptying
Systolic dysfunction
Diastolic dysfunction
Hypertension Myocardial infarction
Diabetes is a risk
factor for diastolic
dysfunction

36
HFpEF
HFrEF
Diagnóstico Clínico
No se justifica la evaluación
ecocardiográfica de rutina

1
1.5
IDENTIFY THE
RISK FACTOR
DIABETES AND CARDI-RENO DISEASE PROTECTION
“CONTROL” THE
RISK FACTOR
REDUCE CV
EVENTS
AVOID SIDE
EFFECTS
The “Virtuous Chain” of Cardio-reno Protection In Diabetes
DIABETES
DIAGNOSIS
REDUCE HB A1C
(“TREAT THE BLOOD TESTS”)
REDUCE CV RISK
(“TREAT THE PATIENT”)
AVOID
IATROGENY
(HYPOGLYCEMIA)

Muchas gracias

RIESGO CARDIOVASCULAR EN EL PACIENTE DIABETICO J GONZALEZ JUANATEY

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