MACROVASCULAR COMPLICATIONS

OF DIABETES.
CARDIOVASCULAR RISC ASSESMENT
IN PATIENTS WITH DIABETES.

1
 Long term vascular complications of diabetes

MACROVASCULAR COMPLICATIONS
Diabetic
MICROVASCULAR COMPLICATIONS

Stroke
retinopathy Two- to four-fold
Leading cause increase in CV
of blindness mortality and
in adults1 stroke2

Diabetic
nephropathy Cardiovascular
Leading cause of disease
endstage renal 65%of individuals
disease2 with diabetes die
from CV events2
Diabetic
neuropathy Peripheral
Leading cause
of non- arterial Disease
traumatic Prevalence of 29% in
lower extremity diabetic people
amputations2 > 50 years3

Most complications arise from damage to small blood vessels and narrowing of
large arteries (atherosclerosis) associated with chronic hyperglycaemia.
Tight control of glycaemia may prevent these complications.
2
1. Cheung N et al. Lancet 2010; 376: 124–36. 2. Deshpande AD, et al. Phys Ther 2008; 88:1254-1264.
3.American Diabetes Association; Diabetes Care 2003;26:3333–3341, 2
MACROVASCULAR COMPLICATIONS OF
DIABETES
Coronary heart disease
• Angina (including silent ischaemia)
• Heart attack (including silent heart attack)
• Sudden death
• Heart failure
• Fainting attacks
Cerebrovascular disease
• Stroke
• Transient ischaemic attack
• Dementia
Peripheral vascular disease
• Intermittent claudication
• Gangrene
• Foot ulcers
3
4
 Cardiovascular Disease (CVD) in
Individuals with Diabetes
• CVD is the major cause of morbidity,
mortality for those with diabetes.
• Common conditions coexisting with type 2
diabetes (e.g., hypertension, dyslipidemia)
are clear risk factors for CVD.
• Diabetes itself confers independent risk.
• Benefits observed when individual
cardiovascular risk factors are controlled to
prevent/slow CVD in people with diabetes.

Prevention, Management of Complications. Diabetes Care

5
2013;36(suppl 1):S28-29
 Cardiovascular Disease (CVD) in
Individuals with Diabetes
• CVD is 2-3 more frequent than in general population;
• premenopausal diabetic women have the same CV risk
as diabetic men;
• CVD is the leading cause of mortality in diabetic
patients (70%–80% of people with diabetes die of
cardiovascular disease);
• CVD mortality rate is 2-4 greater than in general
population;
• for each risk factor present, the risk of cardiovascular
death is about three times greater in people with
diabetes as compared to people without the condition.

6
 Cardiovascular Disease (CVD) in
Individuals with Diabetes

• atherosclerosis is more diffuse, affecting

proximal and distal segments;

• lesion progression is faster and CVD occurs at

younger ages.

7
8
 CORONARY HEART DISEASE IN
DIABETES
• occurs at younger ages (generally with 7-10 years
earlier);
• coronary artery calcification is more extensive, more
diffuse, affecting proximal and distal segments of
an affected artery → implications for coronary
interventions;
• MI incidence in diabetic subjects without a prior MI
is the same as in non-diabetic subjects with a prior
MI.
• in patients with autonomic neuropathy, symptoms
can be atypical or less pronounced;
• higher prevalence of “silent ischaemia” than in
general population;
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 Incidence of MI during a 7-Year
Follow-up in a Finnish Population

50 45.0
Fatal or Nonfatal MI (%)

40 P<0.001

30
18.8 20.2
20 P<0.001

10 3.5

0
Prior MI No prior MI Prior MI No prior MI
Nondiabetic subjects Diabetic subjects
(n=1373) (n=1059)
Haffner SM et al. N Engl J Med 1998;339:229-234. 10
 SYMPTOMS OF CORONARY HEART
DISEASE
• CHD frequently presents without typical
symptoms in individuals with diabetes;
• higher prevalence of “silent ischaemia” than
in general population;
• almost 1/3 of MI in patients with diabetes are
not accompanied by chest pain → underlying
autonomic dysfunction or differences in pain
sensitivity associated with diabetes;
• atypical symptoms: fatigability, atypical
thoracic discomfort, effort-related dyspnoea.
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 PATHOLOGY OF HEART DISEASE IN
DIABETES
• Diabetes is associated with multiple abnormalities
which induce endothelial dysfunction.
• More left main stem disease, more triple vessel
disease than in non-diabetic subjects, coronary
artery calcification is more extensive.
• The development of collateral vessels is reduced.
 Diabetic cardiomyopathy
– can impair systolic emptying or diastolic filling of
the left ventricle
– along with CHD contributes to the high
prevalence of chronic heart failure in people with
diabetes
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 ACUTE CORONARY SYNDROMES IN
DIABETES
• diabetic subjects have an increased incidence of
acute coronary syndromes, and experience poorer
outcomes compared with non-diabetic subjects;

• 20-25% of patients with acute coronary syndromes

also have diabetes;

• represents the cause of death in one of three

subjects with DM ;

• diabetes increases the risk of complications

following an acute coronary syndrome – LV
dysfunction, symptomatic heart failure, recurrent
myocardial ischaemia, requirement for urgent
revascularization, cardiogenic shock, re-infarction,
stroke and death. 13
 PERIPHERAL ARTERIAL DISEASE IN
DIABETES
• Higher prevalence than in general population
(prevalence around 10% in newly discovered type 2
diabetic patients and up to 45% in patients with long
diabetes duration).
• Intermittent claudication is less frequent than in non-
diabetic patients because of the association with
diabetic neuropathy.
• Morbidity and mortality is increased in diabetes, the
disease is more progressive, and the response to
revascularization is less successful than in non-
diabetic subjects.
• More diffuse and distal disease, with more vascular
calcification.
• Diabetes is the first cause of nontraumatic lower
limb amputation. 14
 PERIPHERAL ARTERIAL DISEASE IN
DIABETES
RISK FACTORS FOR PAD IN DIABETES
• Age
• High HbA1c
• Raised systolic blood pressure
• Low HDL cholesterol
• Smoking
• Other CVD
• Retinopathy
• Sensory neuropathy
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 ABI – ankle brachial index
• Normal > 0,9 (0,9-1,2)

• BAP prezentă < 0,9

• Claudicaţie intermitentă < 0,7
• Leziuni multiple, seriate < 0,5
• Durere în repaus < 0,25
• Ischemie critică, gangrenă < 0,2

> 1,3 – Abnormal - vessel hardening from PVD

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18
 INDICELE GLEZNĂ BRAŢ - IGB
• Normal > 0,9 (0,9-1,2)

• arterial disease < 0,9

• moderate arterial disease < 0,7
• devere arterial disease < 0,5
• pain at rest < 0,25

Valori > 1,3 sunt anormale (pacienţi cu

diabet – mediocalcoză; pacienţi cu IRC;
vârstinici cu calcificări intense).
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 CEREBROVASCULAR DISEASE IN
DIABETES
• Risk of ischaemic stroke is increased
threefold in diabetes, and encompasses a
spectrum of disease from large-vessel to
small-vessel occlusive disease.

• Transient ischaemic attacks occur between

two and six times more frequently in people
with diabetes.

• Higher mortality than in general population.

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CARDIOVASCULAR RISK
FACTORS

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 RISK FACTORS
• A risk factor is a condition that places an individual at
risk of developing a health-related problem.
• Can be genetic or acquired.
• It may be identified as a single measurement (eg a
physical feature such as weight), a disease (eg
hypertension) or a lifestyle characteristic (eg smoking).
• In order to be considered a risk factor for a disease, the
condition must be associated with that disease in a
manner which is beyond chance alone. A causal link is
therefore implied. However, a risk factor will not
necessarily always lead to the development of the
disease.
• The ultimate purpose of identifying a risk factor is to
modify it in order to prevent the disease.
Type 2 diabetes,
IDF publication: ‘Diabetes Atlas
theExecutive Summaryand cardiovascular disease22
metabolic syndrome in Europe
RISK FACTORS FOR CARDIOVASCULAR
DISEASE - modifiable
• Diabetes and other high blood glucose
conditions
• Dyslipidaemia
• High alcohol consumption
• Hypertension
• Insulin resistance
• Obesity
• Sedentary lifestyle
• Smoking

IDF publication: ‘Diabetes and Cardiovascular Disease’ 23

RISK FACTORS FOR CARDIOVASCULAR
DISEASE – non-modifiable

• Advancing age
• Genetic background
• Male gender
• Menopause
• Diabetes duration
• Left ventricular hypertrophy

IDF publication: ‘Diabetes and Cardiovascular Disease’

24
 Prevalence of Cardiovascular Risk Factors in Diabetic
Subjects Relative to Nondiabetics

Risk Factor Type 1 Type 2

Dyslipidemia
Hypertriglyceridemia + ++
Low HDL – ++
Small, dense LDL – ++
Increased apo B – ++
Hypertension + ++
Hyperinsulinemia/insulin resistance – ++
Central obesity – ++
Family history of atherosclerosis – +
Cigarette smoking – –
+ = moderately increased compared with nondiabetic population
++ = markedly increased compared with nondiabetic population
– = not different compared with nondiabetic population
Adapted from Chait A, Bierman EL. In: Joslin’s Diabetes Mellitus. Philadelphia: Lea & 25
Febiger, 1994:648-664.
 Prevalence of cardiovascular risk factors in people with
diabetes compared to people without diabetes

Risk factor Prevalence

Hypertension Prevalence is at least double in people with type 2
diabetes.
High blood cholesterol Prevalence is similar in people with diabetes.

High triglycerides with Prevalence is higher in people with diabetes.

low HDL
Left ventricular Most commonly seen in people with long-standing high
hypertrophy blood pressure, but is also seen in the absence of
elevated blood pressure in people with diabetes.
Obesity Prevalence is stronger in people with diabetes.
Weight distribution is also usually different, with more
central obesity which is linked with a tendency to develop
coronary heart disease.
Smoking People with diabetes smoke less (presumably due to
medical advice).

IDF publication: Diabetes Atlas, Executive Summary. 26

RISK FACTORS FOR CARDIOVASCULAR
DISEASE - traditional

• hypertension
• hypercholesterolemia
• smoking
• diabetes

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RISK FACTORS FOR CARDIOVASCULAR
DISEASE – emerging risk factors
• Central obesity
• microalbuminuria
• Reduced GFR
• Endothelial dysfunctin
• Biomarkers (eg highly specific C
reactive protein, fibrinogen, seric A
amiloid, PAI-1, f. von Willebrand,
citokines)
Hoffmeister A et al. Am J Cardiol. 2001;87:262-266. Saito I et al. Ann Intern Med.
2000;133:81-91. Koukkunen H et al. Ann Med. 2001;33:37-47

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METABOLIC SYNDROME - ABDOMINAL
OBESITY

Dyslipidemia

Insulin resistance

Proinflammatory state

Prothrombotic state

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METABOLIC SYNDROME DEFINITION

OBESITY

GLUCOSE INTOLERANCE/
INSULIN RESISTANCE
Cardiovascular
Cardiovascular
T2DM
T2DM disease
ATHEROGENIC DYSLIPIDEMIA disease

HYPERTENSION

WHO, ATP III, IDF, EGIR, AACE, AHA/NHLBI 30

 METABOLIC SYDNROME –
SOCIOECONOMIC IMPORTANCE

Cardiovascular
2x disease

Metabolic
Metabolic
syndrome 3x
syndrome

5x Type 2 diabetes
mellitus

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CARDIOVASCULAR RISK
ASSESMENT

34
 CARDIOVASCULAR RISK FACTORS IN
SUBJECTS WITH DIABETES
• EVALUATED AT DIAGNOSIS AND AT LEAST
ONCE A YEAR.
• dyslipidemia,
• hipertension,
• smoking,
• positive family history for early CHD
• micro- or macroalbuminuria.
• diabetes duration, metabolic control,
presence of chronic complications.
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 Framingham Risk Score
• estimates the 10-year cardiovascular
risk
• 6 risk factors: gender, age, TC, HDL-C,
systolic blood pressure, treatment for
hypertension, and cigarette smoking
status
• Risk:
 low risk (<10%);
 intermediate risk (10-20%);
 high risk (>=20%)
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Step 1: Age
Step 6: Adding Up the Points
Systolic BP Points Points
(mm Hg) if Untreated if Treated
<120 0 0
120-129 0 1
130-139 1 2
140-159 1 2
³160 2 3

HDL-C
(mg/dL) Points
³60 -1
50-59 0
40-49 1
<40 2

37
Expert Panel on Detection, Evaluation, and Treatme
Blood Cholesterol in Adults. JAMA. 2001;285:
38
 Years Points
20-34 -7 Age
35-39 -3
40-44 0 Total cholesterol
45-49 3
50-54 6 HDL-cholesterol
55-59 8
60-64 10 Systolic blood pressure
65-69 12
70-74 14 Smoking status
75-79 16
Point total
Step 2: Total Cholesterol

Note: Risk estimates were derived from the experience of the Framingham Heart Study,
predominantly Caucasian population in Massachusetts, USA.
39
 40
Expert Panel on Detection, Evaluation, and Treatment of
Cholesterol in Adults. JAMA. 2001;285:2
 SCORE Risk Charts
• Total risk estimation using multiple risk factors (such
as SCORE) is recommended for asymptomatic adults
without evidence of CVD.

• High-risk individuals can be detected on the basis of

established CVD, diabetes mellitus, moderate to severe
renal disease, very high levels of individual risk factors
or a high SCORE risk.

• 5 risk factors: gender, age, smoking status, total

cholesterol, systolic blood pressure

• Risk:
 low risk (< 1%);
 moderate risk (1-5%);
 high (>= 5% - <10 %);
 very high risk (>= 10%). 41
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 UKPDS RISK SCORE
• a type 2 diabetes specific risk calculator based
on 53,000 patients years of data from the
UK Prospective Diabetes Study

• UKPDS Risk Engine provides risk estimates

and 95% confidence intervals, in individuals
with type 2 diabetes not known to have heart
disease, for:
non-fatal and fatal coronary heart disease
non-fatal and fatal stroke

• 10 risk factors: gender, age, diabetes duration,

etnicity, atrial fibrilation, smoking status, Hb
A1c, total cholesterol, HDL cholesterol, systolic
blood pressure
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UKPDS RISK SCORE

Risk:
low (<15%),
moderate (15-30%)
high (≥30%).

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 CVD PREVENTION

• Lifestyle optimisation;
• Smoking cessation;
• Glycemic control;
• Hipertension control;
• Hyperlipidemia management;
• Antithrombotic therapy.

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 Recommendations: Glycemic, Blood
Pressure, Lipid Control in Adults
A1C <7.0%*
Blood pressure <140/80 mmHg†
Lipids: LDL cholesterol <100 mg/dL (<2.6
mmol/L)‡
Statin therapy for those with history of MI or
age >40+ or other risk factors
** More or less stringent glycemic goals may be appropriate for individual patients. Goals should be
individualized based on: duration of diabetes, age/life expectancy, comorbid conditions, known CVD or
advanced microvascular complications, hypoglycemia unawareness, and individual patient
considerations.
†Based on patient characteristics and response to therapy, higher or lower systolic blood pressure
targets may be appropriate.
‡In individuals with overt CVD, a lower LDL cholesterol goal of <70 mg/dL (1.8 mmol/L), using a high
dose of statin, is an option.
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Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S33;