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An update for Northern diabetes educators
Cardiovascular disease: the long-term
complication with Diabetes Mellitus
November 20th, 2014
Brian Butkus, PA-C,. MS. AACC
Physician assistant, St. Luke’s Hospital
Depart: Cardiology/Electrophysiology
[email protected]
Presenters Disclosures
NONE
Heart Disease: Atherosclerosis
Slow progressive disease which
begins in childhood.
Plaque in the artery wall forms as a
response to injury to the
endothelium.
Artery narrows and symptoms begin
when >50% blocked.
Diabetes mellitus:
A state of premature cardiovascular
death which is associated with chronic
hyperglycemia.
Fisher BM. Diabetes Mellitus and myocardial infarction: a time to act or a time to wait? Diabetes Medicine.
1998, 15: 275
 2 out of 3 Americans are overweight or obese
 More than 70 million (nearly 1 in 4) Americans have varying
degrees of insulin resistance
 There are an estimated 54 million (more than 1 in 6)
Americans with prediabetes
 Nearly 1 in 4 U.S. adults has high cholesterol
 1 in 3 American adults has high blood pressure
b
V
f
s
o
C
I
d
n
a
t
c
e
r
i
D
Estimated Direct
Medical Costs
Estimated Indirect Costs
Cardiovascular
Disease
$296 billion
$152 billion
Diabetes
$116 billion
$58 billion
TOTAL
$412 billion
$210 billion
(disability, work loss,
premature mortality)
*Note: these figures may not account for potential overlap.
Sources: 2008 statistics from the American Diabetes Association and American Heart Association.
In people with Diabetes:
Heart disease strikes people with DM twice
as often than those without.
Diabetics are 2-4x more likely to suffer
strokes after having had a stroke.
By far the greatest cause of death in people
with diabetes is CVD.
Deaths from heart disease in men with
diabetes have decreased by only 13%
compared to a 36% decreased in number
without diabetes. Why the diff?
DM and all CV-events according to
the Framingham study
Can a Hba1c Predict a MI in
Type 2 Diabetes??
UKPDS 35--Study
So does this mean we should treat
everyone to the lowest attainable
hemoglobin A1c Goal?
Despite clear epidemiology, controversy continues regarding the role
of glucose lowering to prevent coronary events
 This is the position
statement by the
ADA on glycemia
and CVD--2010
NEJM--Advance
--11,140 patient’s randomized.
--Followed 5.9 years.
--There was no evidence that intensive glucose
(Hga1<6.5%) control during the trial led to long-term
benefits with respect to mortality or macrovascular
events.
-- Aggressive A1c (<6.5%) was associated with a
threefold increase risk of hypoglycemia.
Sophia Zoungas, M.D., Ph.D., John Chalmers, M.D., Follow-up of Blood-Pressure Lowering
and Glucose Control in Type 2 Diabetes, NEJM Sept 19th, 2014
What about Insulin
Resistance?
Insulin resistance – the link between CVD
and type 2 diabetes
 Insulin resistance is an independent predictor of CVD2
 Insulin resistance is closely linked to a number of CVD
risk factors3
 Insulin resistance may develop 20+ years before onset of
type 2 diabetes:4 ~50% of newly diagnosed patients
show signs of CVD5
2Bonora
E, et al. Diabetes Care 2002;25:1135–1141. 3Bonora E, et al. Diabetes 1998;47:1643–1649.
4Beck-Nielsen H & The EGIR. Drugs 1999;58(Suppl. 1):7–10. 5Laakso M. Int J Clin Pract Suppl 2001;121:8–12.
6NCEP ATP III. JAMA 2001;285:2486–2497.
Insulin resistance is linked to a range
of CVD risk factors
Insulin resistance
Endothelial
dysfunction
Hypertension
Dyslipidaemia
Microalbuminuria
Vascular
inflammation
Atherosclerosis
CVD
Adapted from McFarlane SI, et al. J Clin Endocrinol Metab 2001;86:713–718.
Prevelance of DM/IGH with pts with CAD.
NGR
Known DM
32%
31%
New DM
IIIGT
IISOLAT IFG
12%
3%
Bartnik MET. a European Heart Journal 2004,25:1880
NGR
Treatment of CAD in the
Diabetic.
Stents,CABG,Meds
Revascularization and
Diabetes
 Patients with DM and multivessel CAD, what
is optimal method of revascularization?
 700,000 patients undergo multivessel
coronary revascularization yearly
 25% of these patients are diabetic
N Engl J Med. 2012 Dec 20;367(25):2375-84. doi:
10.1056/NEJMoa1211585. Epub 2012 Nov 4
History
 Bypass Angioplasty Revascularization
Investigation trial (BARI) in 1997
 Patients w/ multivessel disease assigned randomly
to CABG or PTCA; average follow-up 5.4 yrs
 No difference in mortality overall
 Diabetic subgroup undergoing CABG lived longer
 Led to ACCF/AHA Guideline recommendations:
CABG preferred for revascularization of
multivessel disease in diabetics
N Engl J Med. 2012 Dec 20;367(25):2375-84. doi: 10.1056/NEJMoa1211585. Epub
2012 Nov 4
Circulation.2011; 124: e652-e735Published online before print November 7, 2011,doi: 10.116
History cont: FREEDOM
 Patients undergoing CABG had significantly
lower rates of the primary endpoint including
death from any cause
 Results consistent with reports from smaller,
retrospective, cohort, underpowered and
subgroup analyses in the past
 Previous results had shown major adverse
events were driven by rates of
revascularization. This study shows CABG
benefit driven by decreased MI and death
from any cause.
Diabetics and Coronary
Revascularization in general
Coronary Bypass Surgery
Higher mortality
More frequent complications
infections, delayed wound healing…
Percutanous coronary angioplasty
Higher mortality
Higher restenosis rate
Increased rate of stent thrombosis
More frequent repeat revascularizations
 Statins (also called HMG-CoA reductase inhibitors) work by
increasing hepatic LDL-C removal from the blood.
 Resins (ie, Welchol) bind to bile acids in the intestines and
prevent their reabsorption, leading to increased hepatic
LDL-C removal from the blood.
 Fibrates (also called fibric acid derivatives) activate an
enzyme that speeds the breakdown of triglyceride rich
lipoproteins while also increasing HDL-C.
 Niacin (also called nicotinic acid) reduces the liver’s ability
to produce VLDL. When given at high doses, it can also
increase HDL-C.
American Diabetes Association. Understanding Cardiometabolic risk: Broadening risk Assessment and Management,
Dyslipidemia Richard M Bergenstal, MD International Diabetes Center
 For patients >20 years of age, cholesterol
should be checked every 5 years
 Ordering a fasting lipid panel is preferred to
gauge the patient’s total cholesterol, LDL-C,
HDL-C and triglycerides
 New guidelines based on ASCVD risk score vs
ATPIII guidelines based on treating to targets.
New Recommendations for Diabetics
and statins (LDL:70-189).
--Age 40-75(no CAD): Mod-intens
statin.
--Age 40-75(CAD): High-intens
statin.
2013 ACC/AHA LIPID GUIDELINES
Statins???
Do statins cause diabetes ?
 It is clear that statins can prevent future major
cardiovascular events!!!!!!!!
 Trials do show that Statins can modestly raise blood
sugars.
 In 1 study, diabetes mellitus was diagnosed in 27% more
patients receiving a statin (rosuvastatin) compared with
patients receiving placebo (an identical appearing pill that
does not contain medication), but patients receiving the
statin had a significant 54% lower risk of heart attack, 48%
lower risk of stroke, and 20% lower risk of death from any
cause.
of Min LDL cholesterol) from a meta-analysis of 14 clinical trials risk of experiencing a cardiac
event or death by diabetes status (for a near 40 mg/dL reduction in LDL cholesterol) from a
meta-analysis of 14 clinical trials of statin therapy.
Shah R V , and Goldfine A B Circulation. 2012;126:e282e284
Copyright © American Heart Association, Inc. All rights reserved.
So how much does a statin
increase your glucose?
 Non- diabetics
 Diabetics
Fasting sugars are
increased by 3mg/dl
Increased hemoglobin
A1c by 0.3%
Simsek S, Schalkwijk C, Wolffenbuttel B. Effects of rosuvastatin and atorvastatin on glycemic
control in type 2 diabetes: the Corall Study. Diabet Med. 2012;29:628– 631.
Diabetes and heart failure:
 Numerous trials (HOPE,SOLVD) have found DM
as a major risk factor for the development of
heart failure.
 DM: can cause heart failure independent of CAD
or HTN , via the development of diabetic
cardiomyopathy.
Relation of glucose
tolerance to LV
 Left ventricular size increases with
worsening glucose tolerance– especially in
women.
 Multiple mechanisms have been implicated
in this cause of CHF.
Henry RMA et al. Diabetes care. 2004; 27:522 -529.
Link between DM and Atrial fibrillation cause
or correlation?
--AF is the most common arrhythmia in the world.
--AF is likely multifactorial and the mechanism is
elusive.
--Population based studies suggest DM is an
independent risk factor for AF.
--Most importantly is the fact that DM and AF are
predictors for stroke!!!!!!!!
PREVALENCE OF AF
Prevalence
%
10
8.8
8
6
4.8
4
1.8
2
0.5
0
50-59
60-69
70-79
Age (years)
80-89
PATHOGENESIS
Priorities in the Management of A FIB
The Patient Care Pathway
Rhythm Control
Prevention of
Thromboembolism
Rate Control
CHADS 2 SCORE
C CHF = 1
H Hypertension = 1
A Age >75 years = 1
D Diabetes = 1
S Prior Stroke or TIA = 2
Gage et al. Validation of Clinical Classification Schemes for Predicting
Stroke. JAMA 2001: 285: 22 (2864-2870).
Antithrombotic Therapy
ACC/AHA/ESC Guidelines 2006
Risk Factor
No risk factors
CHADS2 = 0
One moderate risk factor
CHADS2 = 1
Any high risk factor or
>1 moderate risk factor
CHADS2 >2
or Mitral stenosis
Prosthetic valve
Recommended Therapy
Aspirin, 81-325 mg qd
Aspirin, 81-325 mg/d or
Warfarin
(INR 2.0-3.0, target 2.5)
Warfarin
(INR 2.0-3.0, target 2.5)
Warfarin
(INR 2.5-3.5, target 3.0)
Ms. Anderson
 57-year-old female, hasn’t seen doctor in




years
Works as a driver, eats mostly fast food
Smokes 1 pack per day
At health fair found to have BP = 146/86,
total cholesterol = 210
Weight = 200 lbs; Family history of HTN and
diabetes
Chief Complaint:
-SOB
-Jaw discomfort when walking
out in the cold
-Fatigue
Ms. Johnson
46 yo female transferred to SLH by Life Flight with
Chest Discomfort.
-Admits to being diabetic but is on no medications.
-HTN
-Smokes 1-pack cigarrettes
-unknown lipid status
--under initial circumstances, difficult to obtain medical
hx.
Ms Johnson
Her Hemoglobin A1c
8.4%
Risk factors(modifiable) for the prevention
and management of cardiovascular disease:
1. Hypertension
2. Dyslipidemia
3. Smoking cessation
4. Hyperglycemia
Recommendations: Hypertension/Blood
Pressure Control
 Patients with blood pressure >120/80 mmHg should
be advised on lifestyle changes to reduce blood
pressure.
 Patients with confirmed blood pressure higher than
140/80 mmHg should, in addition to lifestyle
therapy, have prompt initiation and timely
subsequent titration of pharmacological therapy to
achieve blood pressure goals.
ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S36
Recommendations: Hypertension/Blood
Pressure Control
 Lifestyle therapy for elevated blood pressure
 Weight loss if overweight
 DASH-style dietary pattern including reducing
sodium, increasing potassium intake
 Moderation of alcohol intake
 Increased physical activity
Antiplatelet and Diabetics
 Consider aspirin therapy (75–162 mg/day)
 As a primary prevention strategy in those with type 1
or type 2 diabetes at increased cardiovascular risk (10year risk >10%)
 Includes most men >50 years of age or women >60
years of age who have at least one additional major
risk factor





Family history of CVD
Hypertension
Smoking
Dyslipidemia
Albuminuria
2010, a position statement of the ADA, the American Heart Association (AHA), and the
American College of Cardiology Foundation (ACCF)
Aspirin continued
 Aspirin should not be recommended for CVD
prevention for adults with diabetes at low
CVD risk, since potential adverse effects from
bleeding likely offset potential benefits
--Low risk: 10-year CVD risk <5%, such as in men <50
years, women <60 years with no major additional CVD
risk factors
ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S40
Treatment
 To reduce risk of cardiovascular events in
patients with known CVD, consider
 ACE inhibitor
 Aspirin*
 Statin therapy*
 In patients with a prior MI
 β-blockers should be continued for at least
2 years after the event
 In patients with symptomatic heart failure,
thiazolidinedione—Black box warning
Take Control of your Eating
--Know what your eating
--Read the labels
--Eat real food
--Don’t combine eating and other activities (TV,
Work,etc)
The problem is that we are not eating food anymore
we are eating food like products!
--Dr. Alejandro Junger
“Walking is man’s best medicine”
---Hipprocrates
1) 150 minutes of mod-intensity aerobic activity week
and
2) Moderate intensity muscle-strengthening 2days wk
“I don’t have time for this type of exercise”
THEN YOU BETTER MAKE TIME FOR ILLNESS!!!!!
What about screening?
Screening
In asymptomatic patients, routine screening
for CAD is not recommended because it does
not improve outcomes as long as CVD risk
factors are treated
In summary: How do we lower the risk for our diabetic patients
in developing CVD:
--Hemoglobin A1c less than 7%
--Control Nonglycemic risk factors:
1) Blood pressure control.
2) Lipid lowering with statin therapy
3) Aspirin therapy
4) Lifestyle modifications
all of these trials confirm that we
need to provide comprehensive care for
diabetes which involve the treatment of all
vascular risk factors-not just hyperglycemia.
???????