In this slide i outlined an open source article, how already 12 years have elapsed over it's publication. I thought it is interesting and i am also sharing it's fulltext link: https://diabetes.diabetesjournals.org/content/56/6/1718

1. Critical Review on an Article
Cihan Durmuş Saydam, 165114006

2. Prevalence and Prognostic Impact of Subclinical
Cardiovascular Disease in Individuals With
Metabolic Syndrome and Diabetes

3. General Information; Why is this topic important
for the authors?
• Presence of subclinical disease in multiple vascular beds has been suggested as an indicator
of overall atherosclerotic burden.
• Consistently literature showed that increased risk of overt cardiovascular disease(CVD) or
Target Organ Damage
• As a commonly agreed opinion established risk factors for overt CVD suggesting developing
definitions of Subclinical CVD,
• Although these premises lack sufficient data or published studies in 2007,
• Metabolic Syndrome(MetS), as a condition associating with clustering of risk factors
including high blood pressure, abdominal obesity, glucose intolerance and dyslipidemia
• Metabolic Syndrome(MetS), carries an increased risk of CVD, it is likely to imagine MetS
have a high burden of subclinical disease
• Previous studies assessing Subclinical Disease in MetS have typically focused on single
measures, so more parameters need to be utilize for more comprehensibly studying value
of subclinical disease for predicting prognosis
• Authors had tested hypothesis that presence of subclinical disease contribute to the
increased risk of overt CVD associated with MetS prospectively,

4. Research Design and Methods
• Design and selection criteria of Framingham Offspring Study; Authors stated
that: “Participants who attended sixth examination cycle elligible to study”
• Routine medical history, physical examination
• (BP measurement, Anthropometry, Laboratory Assessment of CVD Risk Factors, Testing
Presence of Subclinical CVD),
• Definitions of Risk Factors and MetS:
• Cigarette smoking, self report of cigarette use within year preceding heart study
• Diabetes: Fasting Plasma Glucose>126mg/dl
• MetS, definition according to National Cholesterol Education Program Adult Treatment
Panel 3 Criteria, Presence of 3 or more of the following:
• Waist circumference( >102 cm for males, >88 cm for female
• Elevated blood pressure( >130 systolic, >85 diastolic)
• Hyperglycemia(FPG>100mg/dl)
• Hypertriglyceridemia(>150mg/dl)
• Low HDL(<40 mg/dl for males, <50 for females)

5. Research Design and Methods
• Subclinical Disease Measures and Scores:
• Subclinical Vascular Disease and Target Organ Damage
• LV Hypertrophy by electrocardiography and echocardiography,
• LV Systolic Dysfunction by Echocardiography
• Carotid Ultrasound Abnormality, Increased Carotid Artery IMT, Carotid artery stenosis>25%
• Peripheral Arterial Disease, Ankle-Brachial Index<0.9
• Glomerular Endothelial Dysfunction, Microalbuminuria;
• Estimating urine albumin to creatinine ratio measured in a spot urine sample,
• For continuous distribution of values they had dichotomized values using thresholds
• For any abnormalities in 5 tests were considered indicative of subclinical disease
• Periodic examinations at the Framingham Heart Study, and via biennial health history
updates between examinations
• Outcome in that study had been noted as incidence of a first overt CVD event, defined as
composite of coronary heart disease
• recognized or unrecognized Myocardial infarction
• Angina pectoris
• Coronary Insufficiency
• Cerebrovascular disease
• Heart failure
• Intermittent claudication

7. Statistical Methods
• Participants had been categorized in 3 mutually exclusive groups for analyses:
• Those without either MetS or Diabetes; that is Referent Group
• Those with MetS but no Diabetes
• Those with Diabetes
• Multivariable logistic regression to assess the associations of MetS and Diabetes with
prevalence of subclinical disease; adjusting for age and sex;
• Odds ratios for presence of any subclinical disease and for prevalence of each individual
subclinical disease had been estimated for participants with MetS and Diabetes with those
who had neither condition serving as referent,
• Prognostic value/significance of subclinical disease in 3 groups had been evaluated
prospectively;
• Age and Sex adjusted incidence rates of CVD had been calculated for 3 groups overall and
• Stratifying each group by presence of subclinical disease,
• Cox Proportional Hazards Regression, to assess risk of CVD incidence in participants with
MetS and in those with Diabetes
• Effect modification by testing statistical significance of following two-way interaction terms
in multivariable models:
• Subclinical disease by age/sex/MetS/Diabetes
• Two sided p values of <0.05; considered statistically significant;

8. Results-Baseline
• Groups with Diabetes or MetS are (compared
with referent group without diabetes or
MetS)
• Older,
• Higher proportion of male
• Higher levels of BP, FPG, TG, BMI
• Lower HDL level
• More prevalant subclinical vascular
disease
• Strongly and significantly asssociate
with presence of electrocardiographic
and echocardiographic LVH,

9. Results-Odds Ratios
In age and sex adjusted logistic regression
models:
• Increased carotid IMT, stenosis,
microalbuminuria
• Diabetes significantly associate with all
listed characteristics but nevertheless
MetS with exceptions of “LV-Systolic
Dysfunction by Echocardiography” and
“Peripheral Arterial Disease; Ankle-
brachial index<0.9”

10. Results-Incidence Numbers
by 3 Groups and Their
Subgroups According to
Presenting Status of
Subclinical Disease
• On Follow-up(Mean 7.2 years, Range: 0.1-9.0) 139 of 1945 individuals developed a first overt
CVD event; 59 of 581 participants(10.2%) with MetS, 19 of 115 participants(16.5%) with
Diabetes,
• Age/sex adjusted incidence of CVD; Highest rates in participants with diabetes
• Presence of subclinical disease associates with an increased CVD event rate in all 3 groups

11. Results- Age/Sex Adjusted Models
and Multivariable Adjusted Models
• Model A; MetS and diabetes associate with
an increased CVD risk in models without
adjustment for subclinical disease
• Model B; attenuation for both groups,

12. Discussion
• Principal Findings:
1. Over half of the individuals with MetS, had subclinical disease, Prevalence increase
with age, with nearly two-thirds of people with MetS aged>60 years having
evidence of subclinical disease
2. Individuals with MetS with evidence of subclinical disease experience overt CVD
incidence rates comparable with those with diabetes, nearly 3 fold of referent
group
3. Presence of subclinical disease confers approximately 2 fold risk of overt CVD
4. Adjustment for subclinical disease presence attenuates association of MetS and
diabetes with CVD risk
• Important role of subclinical disease in mediating vascular risks associated
with MetS and Diabetes with CVD risk
• Extending previous works establishing this as premise

13. Discussion
• Authors discussed previous studies with this quatations:
• “These prior studies were limited in their focus on specific measurements or
target organs, such as presence of increased left ventricular mass, left
ventricular dysfunction, increased carotid IMT or increased coronary artery
calcium score.”
• “None used a panel of test to comprehensively characterize burden of
subclinical disease associated with condition.”

14. Discussion-Strengths and Limitations
• Strengths:
• Moderate to large community based sample
• Continuous surveillance for CVD events, blinded to subclinical disease status; routine
assessment of comprehensive set of tests of subclinical disease status reflecting
atherosclerotic burden and target organ damage across the cardiovascular system
• Limitations:
• Middle-aged and predominantly white
• Lack of performed imaging allowing evaluation of role of coronary artery calcification
as a marker of subclinical disease in MetS
• Implications:
• “Our results do not imply that individuals with MetS or diabetes should undergo
extensive screening for subclinical disease. The clinical utility of assessment of
subclinical disease burden in these individuals needs to be examined
comprehensively”