Coronary artery disease, Hypertension and Lipids In Diabetes

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Coronary artery disease, Hypertension and Lipids
In Diabetes

• Dr. SURESH PRABU
  
• Dept of Endocrinology
• Christian Medical College
• Vellore

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Case 1

• 58-year-old Mr.A presented to the emergency
  with worsening dyspnoea of 24 hr duration. Two
  days ago he was referred to an orthopedician by
  his family doctor when he had presented with
  acute onset neck pain, shoulder pain and vague
  discomfort.
• He was on irregular drugs for
  diabetes for last 8 years. He had quit smoking 1
  year ago subsequent to the development of right
  leg claudication.

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• On examination his BP was 100/60 mm Hg, had
  crepts over lung base and absent right leg pulse.
  ECG showed fully evolved MI with Q-waves in the
  anterolateral leads. RBS was 326 mg/dl and urine
  ketone was trace positive.

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Questions

• 1. What should have the doctor done when the
  patient presented to him initially?
• 2.What is the most appropriate management of
  diabetes in this patient?
• 3.What is the line of medical therapy to be
  followed on?
• 4. The combination of drugs cannot be used in
  this patient are..

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Case 2

• A 55 year old obese woman came to the OPD for
  check up.She had stopped her anti-diabetic
  medications for last 6 months.Her BP was 160/100,
  HbA1c 8.2 ,FPG - 210,2hr PPBG- 300,TC-
  256,LDL-151,TGL- 286 HDL - 48mg/dl.
• What is the appropriate line of management?

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The problem

• CAD -the main cause of mortality in diabetes.
• Diabetes increasing in epidemic proportions..
• The increasing life expectancy
• - so the numbers are expected to go
  up
• significantly.
• Dyslipidemia and hypertension -the common
• co-morbid condition in diabetes significantly
  affect
• the outcome.
• The crucial role of primary care physician in
  screening and management.

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What is different with diabetes ?

• Coronary artery disease is 3-4 times more
  common.
• Sudden death is higher by 50 in males and 100
  in females.
• Loss of premenopausal protection in females.
• Triple vessel disease, multiple lesions per
  patients and more distal involvement of
  coronary arteries.
• Atypical presentation delays diagnosis.
• LV dysfunction is more common.

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the difference

• Coexisting diabetic cardiomyopathy worsens the
  outcome.
• Revascularization procedures have less favorable
  outcome.
• Restenosis is more common.
• Defective lipid metabolism in diabetes.
• Autonomic neuropathy in diabetes worsens the
  outcome.

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Pathogenesis of accelerated
atherosclerosis

• Hyperglycemia
• Obesity
• Dyslipidemia of diabetes
• Hypertension
• Altered hemorheology
• Oxidative stress
• Hyperinsulinemia

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Clinical Manifestations

• With the classical symptoms of stable angina,
  unstable angina or myocardial infarction.
• Silent or painless ischemic symptoms -dyspnoea,
  hypotension,sweating,syncope or asymptomatic.
• Complications like shock, conduction
  disturbances, cardiac failure, re-infarction and
  ketoacidosis.
• Atypical symptoms - dyspepsia, arm pain,
  toothache, sudden falls, vomiting, and giddiness.
  

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Evaluation

• Resting ECG - has a low sensitivity
• A normal resting ECG does not
  rule out an acute coronary syndrome unless - a
  combination of
• a) Clinical features,
• b) Serial cardiac enzyme and ECGs and
• c) Significant relief with treatment of
  non-cardiac illness
• all have been evaluated to the ultimate
  satisfaction of the treating physician.
  

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Further evaluation

• Stress ECG - excludes triple vessel disease but
  
• not single or double vessel disease.
• Stress Echo - valuable, reliable and
  cost-effective but does not give information on
  the nature of the lesion.
• Angiography - describes the nature and site of
  the lesion but does not give 3D image and
  eccentric lesions are not visualized.
• Nuclear imaging -widespread availability is a
  problem. SPECT and PET assess viable myocardium.

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Management

• Differences in management and outcome are due to
  
• -atypical symptoms
• -requirement of repeated interventions
  and longer hospital stay
• -higher incidence of post-intervention
  complications.
• a higher degree of suspicion during evaluation of
  atypical symptoms and optimization of therapy
  with regular follow-up are vital.
  
  
  

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Behavioral interventions

• Diet -a low fat, low salt and low total calorie.
• Exercise - aerobic exercises
• upper limb exercises
• limit on their level of
  tolerance
• caution on bare foot
  walking or using ill-fitting shoes.
• Reduction of stress in life.
• Cessation of smoking..

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Glycaemic control oral drugs

• Role of optimal glycaemic control (HbA1c lt6.5)
  in preventing or retarding complications of
  diabetes applies to cardiovascular diseases also.
  
• The concern about sulphonylureas
• - hinder ischemic
  pre-conditioning
• - prolonged severe hypoglycemia
  may precipitate an acute coronary event or CCF.
• Are newer sulphonylureas like Glimeperide safe?

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Glycaemic control oral drugs

• Metformin reduces the risk of coronary events
• -first-line therapy in obese
  patients if not contraindicated.
• Thiazolidinediones improve insulin sensitivity
• but cannot be used in obese
  patients and who are prone for volume overload.

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Glycaemic control-The insulin
concern

• Insulin therapy may aggravate
• 
  hyperinsulinemia
• Present consensus - Treatment with insulin
• when needed is not withheld, as
  hyperglycemia
• itself is atherogenic.

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Acute Coronary Syndrome

• No OHA - only Insulin Therapy
• ACE-I Within 24 hrs.
• Cardio-selective beta blockers
• Anti platelets and Thrombolysis
• Anti hypertensives
• Anti lipid therapy
• CABG Vs PTCA

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Glycaemic control acute phase

• Insulin is mandatory during any acute illness.
• Insulin infusion followed by intensive s/c
  therapy influences the outcome significantly.
• Once stable, initiate on short acting insulin,
  followed by once or twice-a-day premixed insulin.
• Frequent monitoring and simple logical dose
  adjustments are the secrets of successful
  management.
• Patient and family education during the acute
  phase can sustain the gains.

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Glycaemic control chronic phase

• In those with chronic complications of diabetes,
  secondary OHA failure and end organ failure
  -continuation of insulin alone is advisable.
• Uncomplicated diabetes Metformin or newer
  sulphonylureas can be initiated and titrated.
• Maintaining a HbA1c values less than 6.5 has
  been proven to be beneficial.

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Hypertension -the problem statement

• Affects 2060 of patients with diabetes.
• Substantially increases the risk of both macro
  vascular and micro vascular complications.
• Increases mortality by 7 folds.
• In diabetic nephropathy increases mortality by
  37 folds.
• 85 of nephropathy patients have hypertension.

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How crucial is BP control ?

• Each 10-mmHg decrease in mean Sbp
• 12 reductions in risk for any
  complication
• 15 for deaths related to diabetes
• 11 for myocardial infarction
• 13 for micro vascular
  complications.

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Classification of hypertension
(JNC-VII)

• SBP
  DBP
• Normal lt120 lt80
• PreHT 120-139 or 80-89
• Stage 1 140-159 or 90-99
  
• Stage 2 gt 160 or gt
  100

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What is the target BP?

• Blood pressures lower than 125/75 mmHg are
• recommended for people who have proteinuria
  
• higher than 1gm/day and renal insufficiency
• regardless of etiology.
• A target blood pressure goal of lt130/80 mmHg is
• reasonable if it can be safely achieved.

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Non-pharmacological management

• Moderate sodium restriction
• Weight reduction
• Moderately intense physical activity
• Smoking cessation and moderation of alcohol
  intake

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Pharmacotherapy of hypertension

• ACE inhibitors and ARBs have a favorable effect
  on renal and cardiovascular systems.
• Diuretics are recommended when BP control is
  still uncontrolled.
• ß-blockers along with ACE inhibitors help in
  reducing myocardial infarction and heart failure.
• Non-DCCBs (i.e., Verapamil and Diltiazem) may
  reduce microalbuminuria. DCCBs (i.e.,Amlodipine)
  in combination with ACE inhibitors, ß-blockers,
  and diuretics help in controlling blood pressure.

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ACE-inhibitors

• ACE-inhibitors 1st drug of choice
• In Type 1 DM , with or without
  hypertension,
• with any degree of albuminuria,ACE-I delay
• progression of nephropathy.
• In Type 2 DM,with hypertension and
• microalbuminuria,ACE-I delays the
  progression of
• nephropathy.
• Side effects -??K ,dry cough, worsening renal
  failure.

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ANGIOTENSIN REC. BLOCKERS

• AR-Blockers are synergistic with ACE inhibitors
• In Type 2 DM with hypertension,
  microalbuminuria
• nephropathy, or renal insufficiency, an ARB
  should be
• initiated or used as add-on drug.
• Side effects- like ACE-I, but no dry cough

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ACE inhibitors and ARBs

• Enalapril -2.5-40mg 5/10mg
• Lisinopril -10-40mg 5/10mg
• Ramipril -2.5-20mg 2.5/5mg
• Losartan -25-100mg 25/50mg
  
  
  
• Telmisartan 20-80mg 40mg
• Irbesartan 150-300mg
• Valsartan 80-320mg

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Beta-blockers and CCBs

• No contraindication for cardio-selective
  blockers.
• Beta blockers particularly in DM with IHD ( like
  in angina or recent myocardial infarction),
  reduce the mortality.
• Side effects Bronchospasm,Pevd,autonomic
  dys.
• NDCCB ( Like Verapamil,Diltiazem are preferred
  to DCCB) are preferably used when other drugs
  are contraindicated.
• Side effects - Heart blocks.

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Other antihypertensives

• Diuretics - Add on to ACEI/ARB
• If creatinine lt1.8 Thiazides (e.g-
  Indapamide)
• If creatinine gt1.8 Loop diuretics(e.g-
  frusemide)
• CCF - Loop diuretics Frusemide (20-320 mg/d)
• Ksparing diuretic Spironolactone
  (25-100mg/d)
• Side effects-worsening hyperglycemia, Hypokalem
  ia.
• Alpha blockers - DMBPH
• Side effects -Adverse cardiac events

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When to start therapy?

• Bp should be measured at every visit both in
  the
• sitting and lying down positions.
• SBP gt130, DBP gt 80 - needs repeated readings.
• SBP of 120139 mmHg or a DBP of 8089 mmHg
• requires lifestyle/behavioral therapy for a
  maximum of
• 3 months.
• SBP gt 140 mmHg or DBPgt 90 mmHg should receive
  drug therapy in addition.

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Special situations

• Ischemic Heart Disease
• Stable angina beta blockers or long acting
  CCBs
• Unstable angina/MI beta blockers ACE
  Inhibitors
• Post MI CCFACE-Is beta blockers
• 
  aldosterone antagonists
• Pregnancy
• Alpha methyldopa, vasodilators and calcium
  channel blockers are safe

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Special situations

• Renal Disease
• In the presence of microalbuminuria, ACE-I or
  ARBs are the preferred drugs.
• An increase in sr. creatinine up to 35 above
  baseline is acceptable, unless serious
  hyperkalemia develops.
• Sr.creatinine gt3mg/dl is a C/I for AACEI/ARB.
• They are stopped and are replaced by NDCCB
  or centrally acting drugs like Alpha methyldopa
  and vasodilators.

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Follow-up

• Monitor renal function and serum potassium
  levels.
• Reinforce lifestyle modification.
• Reassess adherence, weight, alcohol, acute life
  
• stress and co-existing medical problems.
• In elderly people, BP should be lowered
  gradually.
• Titrate initial drug, add or substitute another
  agent.
• Patients not controlled on 3 drugs- including a
  diuretic, and /or if with significant renal
  disease should be referred to a specialist.

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Cardio protective drugs

• Anti-platelet drugs Aspirin and Clopidogrel
  
• ACE inhibitors
• reduce cardiac remodeling,
  infarct size,
• improve endothelial function and
  fibrinolysis.
• Beta-blockers
• cardio-selective drugs reduce
  sympathetic load on the heart and improve the
  outcome.
• As a primary prevention strategy aspirin is
  recommended in those with risk factors like
  hypertension, smoking and dyslipidemia.

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Surgical intervention

• PTCA (Percutaneous Transluminal Coronary
  Angioplasty)
• less effective due to extensive
  disease and re-stenosis
• CABG (Coronary bypass grafting) with internal
  mammary artery
• -is better than bypass
  grafting with the saphenous vein and more
  effective than PTCA.
•     

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Dyslipidemia in diabetes -
the unique alterations

• Hypertriglyceridemia High FFA
• Cholesterol rich and small
  dense VLDL
• HDL Ineffective
• Triglyceride rich HDL
• LDL Dangerously modified
• Small dense ,Glycated
  oxidated LDL

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Categories of risk (based on
Lipoprotein levels in mg/dl )

• Risk Total-C LDL-C HDL-C
  TGL
• High gt240 gt130 lt35
  gt400
• Border 180-239 100-129 35-40
  150-399
• line
• Low lt180 lt100
  gt40 lt150

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Management of dyslipidemia

• In all patients with diabetes and IGT check
  lipid
• profile at diagnosis and during annual
  screening.
• R/o alcohol, estrogen use, physical inactivity,
• renal impairment, hypothyroidism, steroids,
• diuretics and familial hyperlipidemia.
• Diet - reduces LDL cholesterol 1525 mg/dl.
• carbohydrate - 50 to 60 , fat
  - 24 to 28
• protein 10 to 15 , Saturated
  falt 7 ,
• mufa and pufa 10 each of the
  total fat.
• The total cholesterol intake lt200 mg / day.

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Management of dyslipidemia

• Physical activity help in reducing TGL LDL
  levels and in increasing the HDL levels.
• Diabetic control improves lipids in Type1 DM
  but in Type2 DM,some lipid abnormalities
  persist.
• Glucose-lowering oral agents have main effect
  on TGL only a minimal effect on HDL levels.
• Lifestyle interventions should be monitored at
  regular intervals, with consideration of
  pharmacological therapy between 3 and 6 months.

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Management of dyslipidemia-LDL

• If gt 1 risk factors for cardiovascular disease,
  
• -treatment is initiated even when
  the
• LDL gt 100mg/ dl. Aim for reduction by 30-40
• of the baseline value.
• If no risk factors
• -therapy is usually initiated when
  LDL level is
• persistently gt 130 mg/dl even after
  strict behavioral
• therapy.
• 
  

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Management of dyslipidemia-TGL

• TGL levels improve significantly with blood
  glucose control alone.
• Treatment with drugs is initiated
• -if the TGL levels are persistently high
  even after satisfactory blood glucose control.
• -or if the initial values are gt400 mg/dl
  as the risk of pancreatitis increases.

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Drug therapy- Choice of drugs

• ? TGL ? HDL
• 1st choice - Fibric acid derivatives
  
• 2nd choice-HMG-Co-A RI (Statins)
• 3rd choice Nicotinic acid
• ? LDL
• 1st choice - Fibric acid derivatives
  
• 2nd choice-HMG-Co-A Reductase
  inhibitor
• ?? LDL ? TGL
• High dose statins

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• Fibric acid Derivatives
• Reduce TGL by 2550,raise HDL-C by 15 25.
• Gemfibrozil-600mg bid Fenofibrate 60-200mg
  qd
• HMGCoA RI
• Reduce LDL 50 , triglyceride by 25 .
• Lovostatin-10-80mg qd, Simvastatin - 5-80
  mg qd
• Atorvostatin-10-80mg qd,Rosuvastatin-10-40mg
  qd
• Serious side effect- myositis(lt1)
• Asymptomatic liver enzyme elevation
  (lt2)

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• Nicotinic acid
• TGL reduced by 20-50 , raises HDL by 15-35 ,
  reduces LDL by 5-25
• Dose - 1.5 to 3 gm /day
• Side effects Hyperglycemia,Skin flushing,
• ? liver enzymes ,GI irritation, ocular
  toxicity

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Newer agents

• Ezetimibe - 10 mg once a day dose
• impairs cholesterol absorption and
  ?hepatic delivery, ?hepatic uptake Primarily
  LDL lowering effect. Used as monotherapy or as
  add- on therapy.
• Policosinol - 10 mg per day
• studied in older subjects with
  dyslipidemia, also
• has antiplatelets action in addition to LDL
• lowering effect.

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Monitoring

• Targets (in mg/dl)
• HDL gt40 (gt50 in women)
• TGL lt 150
• LDL lt100
• Total cholesterol lt 180. 
• Therapy is monitored with muscle enzymes and
  liver
• enzyme estimation.Discontinue if liver enzymes
  are
• increased by 10 times the basal values.
• Reduce dose of drugs and monitor renal
  functions
• while combining with fibrates.

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• Co-existing conditions Preference of drugs
• 1.Htn with stable angina - Anti platelets
• 
  Beta-blockers
• 2.CAD with
• LV dysfunction - ACE-I,
  Diuretics,
• 
  Antiplatelets
•  
• 3.CAD with coronary stent - Anti platelets,
  
• 
  Clopidogrel, Statins
• 4. CAD with Nephropathy - ACE-I, AR2-B,
• 
  Anti platelets

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Case 1

• 1. The doctor should have done the following
  when the patient presented to him initially
• Suspected ischemic cardiac disease.
• a) taken ECG and given Aspirin.
• b)Checked his blood glucose and urine
  ketones.
• c)referred to physician or cardiologist
• particularly when a smoker with diabetes and
• vascular disease presents with acute onset
• symptoms.

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Case 1

• 2.The most appropriate management of Diabetes is
  to initiate insulin in the acute phase and
  continue on a long term basis.
• 3.Management of acute coronary syndrome,
  glycaemic control with insulin and subsequent
  patient education on compliance and lifestyle
  with stress on long term follow up.
• 4.Combination of drugs
• To be used -Insulin, aspirin, statins,
  ACEI
• Cannot be used -Beta blockers and OHAs

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Case 2

• 1.Optimization of glucose control.
• 2.Behaviour therapy and statins.
• 3. Renal parameters and ACE-I/ARBs.

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The vital targets

• HbA1C lt 6.5
• LDL lt 100 mg/dl
• BP lt 125 / 75mmHg

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Summary

• Blood Glucose, Blood Pressure,
• ECG,Lipids, Urine Microalbumin, Creatinine
• Exercise,Life Style Diet
• Medications
• Monitor
• Targets
• Referral