METABOLIC SYNDROME IN CARDIOVASCULAR DISEASE

Managing the undertreated risk factors

Fahmi Idrus
Division of Critical Care and Clinical Cardiology
Department of Cardiology and Vascular Medicine
Faculty of Medicine, Universitas Indonesia

Abstract
The metabolic syndrome is a complex of interrelated risk factors for cardiovascular disease
(CVD). These factors include dysglycemia, raised blood pressure,elevated triglyceride levels,
low high-density lipoprotein cholesterol levels, and obesity (particularly central adiposity). This
increasingly important proinflammatory condition remains both underrecognized and
undertreated. Previous studies demonstrated that a cluster of risk factors, including abdominal
obesity, hypertension, impaired fasting glucose, and dyslipidemia, was strongly associated with
the risk of coronary artery disease (CAD). Clinicians should identify individuals with this
condition, assess their cardiovascular risk and treat them by an aggressive and multifaceted
approach. We report a case of Acute Heart Failure in Acute Coronary Syndrome with Metabolic
Syndrome in 39 years old man. Before addmission, his metabolic state was undertreated. He
underwent coroangiography with result of CAD 3 vessel disease. Five months prior the
admission, his left ventricular ejection fraction was 65% which then dropped to 22% by the time
of hospitalization (within five months).

Introduction
Increased caloric intake, increased consumption of refined carbohydrates, and physical
inactivity have led to an explosion in the incidence of abdominal obesity and an emerging
epidemic of insulin resistance. Abdominal obesity has tripled in the United States during the past
4 decades, currently affecting half of all adults. More than one quarter of the US population has
the metabolic syndrome, and the incidence is increasing. In association with increasing obesity,
the age adjusted prevalence of the metabolic syndrome in the US population aged 25 years or
older has increased from 24% in 1988-1994 to 27% in 1999-2000, and in those older than
60 years, the prevalence is more than 40%.

The metabolic syndrome is a predictor of type 2

diabetes mellitus and future cardiovascular events. 1,2

Data from National Cardiovascular Center Harapan Kita (NCCHK) registry from 20082010 identified that coronary artery disease (CAD) with hypertension and diabetes mellitus as
comorbids were around 83 to 142 cases per year.

Figure 1. The incidence of coronary artery disease with hypertension and T2DM at NCCHK in
2008

Figure 2. The incidence of coronary artery disease with hypertension and T2DM at NCCHK in
2009

Figure 3. The incidence of coronary artery disease with hypertension and T2DM at NCCHK in
2010

Aim of Presentation
To discuss the management of metabolic syndrome in patient with coronary artery disease.
Case Ilustration
A 39 year-old man was referred from clinic to the emergency department (ED) of
National Cardiovascular Center Harapan Kita (NCCHK) on August 18th 2011 at 03.37 p.m. His
chief complaint was shortness of breath associated his chest liked being crushed by something
heavy with since 13 hours before he came to ED of NCCHK, he was sleeping at that time. He
also complaint for pain at the upper abdominal region through his back, the duration of pain was
about 30 minutes. He told that his upper abdominal just liked being squeezed. He realized that he
had massive cold sweat with nausea but no vomiting. He took isosorbid dinitrat 5mg SL at that
time, the pain was decreased but not fully disappear. Since that, he easily fatigue when he walk,
even to the bathroom. He denied of having swollen extremities, face, and abdominal region. He
sleeps with 1 pillow and never woke up due to difficulty in breathing before. He thought that he
only had gastritis for the first time, so he just put some oil on his back and asked her wife for
some massages. Two hours before he admitted to the ED of NCCHK, he went to a clinic, and he
was given aspirin 1x80 mg, clopidogrel 1x75 mg, omeprazole 1x1 cap, isosorbid dinitrat 5mg
SL, bisoprolol 1x2,5mg.
Five months before the patient came to ED, March, 2011, he was referred from RS.
Patria with consultation form to underwent echocardiograpy at NCCHK, due to his chest pain in
the lower region through his back, < 10 minutes, without massive cold sweat, nausea and
vomiting. The chest pain resolved by rest. The echocardiography was performed on March 14 th
2011. The echocardiography showed, the end diastolic diameter (EDD) was 52 mm and the end
systolic diameter (ESD) was 33 mm. The Left Ventricle (LV) systolic function was normal with
ejection fraction (EF) 65%, the right ventricle (RV) function was normal also with trans-annular
plane (TAPSE) 2,3cm. All the valve morphology and function were normal. The mPAP was 5
mmHg, E/A<1.
Three months before he came to ED, he had chest pain in the lower region through his
back, the pain quality just like when he came to ED, but with shorter duration, not longer than 10
minutes. It came when he was sitting at his office. He thought that he had gastritis. No massive
cold sweat, nausea and vomiting at that time. He just drank water, and the pain was disappeared.

Two days before admitted, he went to RS Patria for consultation about his hypertension
and diabetes. He was given isosorbid dinitrat 3x5 mg, glimepiride 1x2 mg, metformin 3x500 mg,
and amlodipine 1 x 10 mg.
Patient reported that he has hypertension and diabetes for the last 2 years, and he was not
taking medicine regularly.
From the examination at the emergency room, patient was still have a shortness of breath
and a little bit chest pain. He was fully alert and conscious. Patient weight was 94 kg, the height
was 167 cm, and the Body Mass Index (BMI) was 33.7 kg/m2. The blood pressure was 165/113
mmHg and the pulse rate was 100 per minute with regular and good pulse. The respiratory rate
was 24 times per minutes. The body temperature shows normal limit. The scleras were not
icteric, and the conjunctivas were not anemic. The jugular venous pressure (JVP) was 5-2
cmH2O. In the cardiac examination we heard regular first and second heart sounds. The lung
examination was vesicular sounds, with rales at the base of both lungs and no wheezing. From
the abdominal examination, the circumference was 121 cm, the liver and spleen were not
palpable. Both extremities were warm and no swelling.
The electrocardiogram (ECG) (figure 4) in the ED was sinus tachycardia with QRS rate
100 beats per minutes, QRS axis was normal, P wave was normal, PR interval was 0,16 seconds,
QRS duration was 0,08 seconds, ST-depression om I, aVL, V6, T inverted in lead I, aVL, V5-V6,
Q-wave in V1-V4. The conclusion of this ECG was: Old anteroseptal MCI with ischemic lateral.

Figure 4. The ECG on admission, August 18th 2011.

The chest x-ray ( Figure 5), taken on August 18th 2011, showed the cardio-thoracic ratio
53%, elongation of aortic segment, normal pulmonal segment, waist of heart was flat, downward
apex, there were congestions at the base region of the lung.

Figure 5. Chest X-ray, August 18th, 2011

The laboratory examination showed elevated of cardiac enzym Trop-T 0,064 ng/ml,
CKMB was 19 u/L. Lipid profile showed dislipidemia, with total cholesterol 219 mg/dl, HDL 25
mg/dl, LDL 144 mg/dl, triglycerides 264 mg/dl, the HbA1C was 8.3%,and the CRP was 10
mg/L. NT-pro BNP was 1554. Hematology routine, random blood glucose, renal function and
electrolyte were within normal limit.
The diagnosis were Acute Heart Failure e.c Acute Coronary Syndrome (NSTEMI TIMI
Risk 4/7, GRACE Score 101), Hypertension Stage II, and Diabetes Mellitus Type 2.
The medication was given at the emergency department were NTG drip 5 mcg/minutes,
aspirin loading 160 mg, clopidogrel loading 300 mg, isosorbid dinitrate 3 x 5 mg, simvastatin 1
x20 mg, laxadine 1 x C1, diazepam 1x 5 mg, heparinisation with enoxaparine 2 x 0,6 ml. The
fluid intake was 2000 cc/24 hours, and the caloric need was 2100 kkal/24 hours.

On the 2nd day of care at intermediate ward (August 19 th, 2011), the complaint of chest
pain decreased. Shortness of breath decreased also. The blood pressure was 136/83 mmHg, heart
rate was 85 per minutes, respiratory rate was 20 per minutes, and no febris. From lung
examination, there were still rales at the base region. The additional therapy was bisoprolol 1x5
mg, isosorbid dinitrate was uptitrated to 3x 10 mg, glimepiride 1 x 2 mg, metformin 1x 500 mg.
The other therapy was continued.
On the 3rd day of care( August 20th, 2011), the complaint of chest pain had diminished but
sometimes he still felt heavy on his chest. The blood pressure was 135/80 mmHg, heart rate 86
per minutes, respiratory rate was 18 per minutes, oxygen saturation was 100%. The additonal
therapy was diltiazem 1 x100 mg, and ramipril 1 x 5 mg. The NTG had been tapp off. The other
therapy was continued. The patient was scheduled for coroangiography on Monday, August 22 nd
2011.
On the 5th day of care (August 22 nd, 2011), the patient went to the cath lab. Before the
procedure started, in the cath lab, the patient was complaining about shortness of breath. In the
physical examination, the rales was heard at the basal region of the chest. Because of that
shortness of breath, the procedure was postponed.

The therapy of diltiazem was stopped,

ramipril was uptitrated to 2 x 5mg, furosemid 1 x 20 mg intravenous was added. The other
therapy was continued. The NT-pro BNP was checked, and also echocardiography evaluation.
The NT-pro BNP was 1554. .
The patient underwent echocardiography evaluation on August 23rd, 2011. It showed a
decreased function. The EDD was 63 mm and the ESD was 57 mm. The global LV contractility
has decreased with EF 22%, the RV function also decreased with TAPSE 1,3 mm. The segmental
analysis showed a global hypokinetics. The mitral valve examination showed mild mitral
regurgitation (functional). The mPAP was 30 mmHg, E/A > 1.

Figure 6. The echocardiography on August 23rd 2011

On the 7th day of care ( August 24th 2011), the patient was removed to the adult ward. The
patients has no shortness of breath nor of chest pain. The blood pressure was 142/105 mmHg,
the heart rate was 80 per minutes, the respiratory rate was 18 per minutes. There rales was not
heard anymore. The therapy was continued. The patient was rescheduled for coroangiography
on Thursday, August 25th, 2011.
On the 8th day of care ( August 25th, 2011) The patient condition was stable. The blood
pressure was 128/86 mmHg, heart rate 76 per minutes, respiratory rate 18 per minutes. The other
physical examination were in normal limit. The patient underwent coroangiography. The result
was; LM: normal; LAD: multiple stenosis from proximal to mid 70 -80 %; LCx: Multiple
stenosis 70-80% at mid; RCA: Stenosis 70% and PDA 80%. The conclusion was CAD 3 vessels
disease. Suggestion was CABG.

The patient was discharged after 8 days of care, with a stable hemodynamic. The chest
pain had resolved, the shortness of breath had disappeared, and he could sleep with 1 pillow. He
was scheduled for Thallium scanning examination on September 20th 2011. The patient went
home with therapy aspirin 1x80 mg, clopidogrel 1x 75 mg, simvastatin 1x20 mg, bisoprolol 1x5
mg, glimepiride 1x 1 mg, metformin 2x500 mg, ramipril 2x5 mg, furosemid 1x 40 mg, isosorbid
dinitrate 3x 5mg, isorbid dinitrate 5mg SL if necessary.
DISCUSSION
The National Cholesterol Education Programs Adult Treatment Panel III (NCEP/ATP
III) report identified metabolic syndrome as a constellation of risk factors that increase a persons
risk of developing cardiovascular disease (CVD). ATP III identified 6 components of the
metabolic syndrome that relate to CVD; Abdominal obesity, atherogenic dyslipidemia, raised
blood pressure, insulin resistance/ glucose intolerance, proinflammatory state, prothrombotic
state. When 3 of 5 of the listed characteristics are present, a diagnosis of metabolic syndrome can
be made. The WHO criteria require insulin resistance for diagnosis, by demonstrating the
presence of type 2 diabetes, IFG or IGT by OGTT in patients without IFG. In addition to insulin
resistance, two other risk factors are sufficient for a diagnosis of MS. Recently, IDF and
AHA/NHLBI representatives held discussions to attempt to resolve the remaining differences
between definitions of metabolic syndrome. Both side agreed that abdominal obesity should not
be a prerequisite for diagnosis but that it is 1 of 5 criteria, so that the presence of any 3 of 5 risk
factors (elevated waist circumference, reduced HDL, elevated triglycerides, raised blood
pressure, elevated fasting glucose glucose intolerance) constitutes a diagnosis of metabolic
syndrome. Most persons with the metabolic syndrome are overweight or obese; clinical studies
have noted a high correlation between abdominal obesity and the risk factors characteristic of the
metabolic syndrome. 3,4,5,6

Table 1. Current Clinical Definitions for Metabolic Syndrome. IDF/AHA6

Table 2. Current Recommended Waist Circumference Thresholds for Abdominal Obesity by

Organization 6

In this patient, the weight was 94 kg, the height was 167 cm, and the Body Mass Index
(BMI) was 33.7 kg/m2. From the abdominal examination, the waist circumference was 121 cm,
the blood pressure was 165/11mmHg. The lipid profile show, the HDL 25 mg/dl, LDL 144
mg/dl, triglycerides 264 mg/dl, cholesterol 219 mg/dl. According to the IDF/AHA criteria, we
can diagnose this patient with metabolic syndrome.
Data from recent meta-analyses indicate that people with metabolic syndrome have a 2fold increase in CV outcomes and 1.5-fold increase in all-cause mortality.7

Pathophysiology of cardiovascular disease in metabolic syndrome

Figure.7. Pathophysiology of cardiovascular disease in metabolic syndrome 9

Clinical Management of Metabolic Syndrome

The primary goal of metabolic syndrome is to reduce risk for clinical atherosclerotic
disease. For individuals with established diabetes, risk factor management must be intensified to
diminish their higher risk for atherosclerotic cardiovascular disease (ASCVD). The prime
emphasis in management of the metabolic syndrome per se is to mitigate the modifiable,
underlying risk factors (obesity, physical inactivity, and atherogenic diet) through lifestyle
changes.8
Practical ABCDE Approach for Metabolic Syndrome in Coronary Artery Disease.
Assesment & Antiplatelet
The first step in treatment is recognition the clinical condition. Review current and prior
cardiovascular medical and surgical diagnoses and procedures (including assessment of left
ventricular function); comorbidities (including peripheral arterial disease, cerebral vascular
disease, pulmonary disease, kidney disease, diabetes mellitus, musculoskeletal and
neuromuscular disorders, depression, and other pertinent diseases); symptoms of cardiovascular
disease; medications (including dose, frequency, and compliance); cardiovascular risk profile.
In second place,

we should do some

physical

examinations

and 12-lead

electrocardiography. Document the patient assessment information, interactively, communicate

the treatment and follow-up plans with the patient and appropriate family, ensure that the patient
is taking appropriate doses of medicine.10
Use aspirin for CHD patients to reduce prothrombotic state.12 This patient was given
aspirin 1x80 mg and clopidogrel 1x75 mg for antiplatelet.
Blood pressure management
Measure blood pressure, assess current treatment and compliance. Assess use of
nonprescription drugs that may adversely affect blood pressure. If blood pressure is 120-139 mm
Hg systolic or 80-89 mm Hg diastolic: Provide lifestyle modifications, including regular physical
activity/exercise; weight management; moderate sodium restriction and increased consumption
of fresh fruits, vegetables, and low-fat dairy products; alcohol moderation; and smoking
cessation. Provide drug therapy for patients with chronic kidney disease, heart failure, or diabetes
if blood pressure is 130/ 80 mmHg after lifestyle modification. If blood pressure is 140

mmHg systolic or 90 mmHg diastolic: Provide lifestyle modification and drug therapy.
Continue to assess and modify intervention until normalization of blood pressure in
prehypertensive patients; <140 mmHg systolic and <90 mmHg diastolic in hypertensive patients;
<130 mmHg systolic and <80 mmHg diastolic in hypertensive patients with coronary artery
disease, diabetes, heart failure, or chronic kidney.11
The hypertension in this patient was treated with bisoprolol 1x 5mg, ramipril 2 x5 mg.
The hemodynamic when he was discharged was stable with blood pressure 126/80 mmHg.
Cholesterol level management
First, we should obtain fasting measures of lipid profile. If the result in abnormal levels,
obtain a detailed history to determine whether diet, drug, and/or other conditions that may affect
lipid levels can be altered. Assess current treatment and compliance. Repeat lipid profiles at 4-6
weeks after hospitalization and at 2 months after initiation or change in lipid-lowering
medications. In patient with type 2 diabetes and cardiovascular disease or chronic kidney disease
the LDL goal < 70 mg/dl and the secondary goal for non HDL < 100 mg/dl.13
The dyslipidemia in this patient was treated with simvastatin 1x 20 mg.
Diabetes & diet management
The mortality rate in diabetic subjects who have experienced CHD is much higher than in
non-diabetic subjects. First, we should confirm presence or absence of diabetes in all patients. If
a patient is known to be diabetic, identify history of complications such as findings related to
heart disease; vascular disease; problems with eyes, kidneys, or feet; or autonomic or peripheral
neuropathy. Obtain history of signs/symptoms related to above complications and/or reports of
episodes of hypoglycemia or hyperglycemia. Intensive lifestyle modification for all patients is
necessary.
In those taking insulin or insulin secretogogues, avoid exercise at peak insulin times, and
advise that insulin be injected in abdomen, not muscle to be exercised. Test blood sugar levels
pre- and postexercise at each session: if blood sugar value is <100 mg/dL, delay exercise and
provide patient 15 g of carbohydrate; retest in 15 minutes; proceed if blood sugar value is >100
mg/dL; if blood sugar value is >300 mg/dL, patient may exercise if he or she feels well. Caution
patient that blood sugar may continue to drop for 24-48 hours after exercise.

Long-term target is attain FPG levels of 90-130 mg/dL and HbA1c <7%, minimize
complications and reduce episodes of hypoglycemia or hyperglycemia at rest and/or with
exercise. Maintain blood pressure at <130/<80 mm Hg.15
The disglycemia in this patient was treated with glimepirid 1x 1 mg and metformin 2x
500mg. The random blood glucose when he was discharged was 144 mg/dl.
Weight loss has been shown to reduce oxidative stress and to improve each of the
components of the metabolic syndrome.14
Since the admission, the patient body weight reduced from 94 kg to 89 kg when he was
discharged.
Diet for metabolic syndrome; increase omega-3 fatty acids, fruits, vegetables, fiber, nuts,
and low glycemic load diet. This patient was consulted to the nutritionist. The total calories for
this patient was 1800 kcal/24 hours. The composition for his meal are 40% of carbohydrate, with
low purin and low fat. For the snack are fruit and vegetables..
Exercise
Symptom-limited exercise testing prior to participation in an exercise-based cardiac
rehabilitation program is strongly recommended. The evaluation may be repeated as changes in
clinical condition warrant. Test parameters should include assessment of heart rate and rhythm,
signs, symptoms, ST-segment changes, hemodynamics, perceived exertion, and exercise
capacity. Exercise prescription should specify frequency (F), intensity (I), duration (D),
modalities (M), and progression (P).
For aerobic exercise: F = 3-5 days/wk; I = 50-80% of exercise capacity; D = 20-60
minutes; and M = walking, treadmill, cycling, rowing, stair climbing, arm/leg ergometry, and
others using continuous or interval training as appropriate.
For resistance exercise: F = 2-3 days/wk; I = 10-15 repetitions per set to moderate
fatigue; D = 1-3 sets of 8-10 different upper and lower body exercises; and M = calisthenics,
elastic bands, cuff/hand weights, dumbbells, free weights, wall pulleys, or weight machines.
The expected outcome from exercise are; Patient achieves increased cardiorespiratory
fitness and enhanced flexibility, muscular endurance, and strength. Patient achieves reduced
symptoms, attenuated physiologic responses to physical challenges, and improved psychosocial
well-being.16

Summary
A case of 39 year-old man came with chief complain was shortness of breath associated
his chest pain. The patient was diagnosed as Acute Heart Failure in Acute Coronary Syndrome
(NSTEMI TIMI Risk 4/7, GRACE Score 101), Hypertension Stage II, and Diabetes Mellitus
Type 2. From the examinations, the patient fulfilled all of criteria for metabolic syndrome. The
untreated risk factors before led him to coronary artery disease. The patient was discharged in a
stable hemodynamic state. The planning for this patient is to control and monitor the
cardiovascular risk factors.

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