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Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 73-76

A study of endothelial function by flow-mediated vasodilatation in patients with metabolic syndrome

Department of Medicine, BMCRI, Bengaluru, Karnataka, India

Date of Submission09-Sep-2019
Date of Acceptance05-Jan-2020
Date of Web Publication18-Apr-2020

Correspondence Address:
Dr. Diwakar Tumkur Narsimhamurthy
No. 155/2, Sannidhi, 4th Cross, Byrasandra, C V Raman Nagar, Bengaluru - 560 008, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AJIM.AJIM_50_19

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Background: Metabolic syndrome (MetS) is characterized by clustering of cardiovascular risk factors.Endothelial dysfunction is the key early event in atherogenesis that occurs long before structural atherosclerotic changes and promotes cardiovascular events. The assessment of endothelial function by flow-mediated dilation (FMD) of the brachial artery has been proposed as a non-invasive marker for cardiovascular risk. Aim: Assessment of flow mediated vasodilatation of brachial artery as a non invasive marker of endothelial function in metabolic syndrome and To assess the relationship of number of risk factors in metabolic syndrome with endothelial dysfunction. Methodology: A case control study in which 50 patients with Metabolic Syndrome as per new IDF criteria and 50 controls were studied. Detailed clinical history, examination and Blood investigations like Fasting blood glucose, fasting lipid profile and ECG was done for every patients. Endothelial function was assessed by brachial artery flow mediated vasodilatation. Results: In the present study 100 (50 cases and 50 controls) patients were studied, males (54%) and females (46%), majority in the age group between 40-60 years (mean age - 49.76 ± 13.76yrs in cases and 44.94 ± 16.09 years among controls). We identified a significant difference between cases and age- and sex-matched controls regarding brachial artery FMD% (7.24 ± 5.24 and 21.29 ± 9.29 respectively; P value-0.000). Negative corelations were found between FMD% and various variables and also between number of components and FMD% (r = -0.239). Conclusion: MetS is associated with endothelial dysfunction as evidenced by decreased FMD% compared to controls. There is a negative correlation between various components of MetS, number of components of MetS and FMD%.

Keywords: Cardiovascular disease, flow-mediated vasodilatation, metabolic syndrome

How to cite this article:
Hegde SV, Narsimhamurthy DT. A study of endothelial function by flow-mediated vasodilatation in patients with metabolic syndrome. APIK J Int Med 2020;8:73-6

How to cite this URL:
Hegde SV, Narsimhamurthy DT. A study of endothelial function by flow-mediated vasodilatation in patients with metabolic syndrome. APIK J Int Med [serial online] 2020 [cited 2020 Jul 11];8:73-6. Available from: http://www.ajim.in/text.asp?2020/8/2/73/282847

  Introduction Top

Metabolic syndrome (MetS) (syndrome X and insulin resistance syndrome) consists of a constellation of metabolic abnormalities that confer an increased risk of cardiovascular disease (CVD) and diabetes mellitus.

The major features of MetS include central obesity, hypertriglyceridemia, low levels of high-density lipoprotein (HDL) cholesterol, hyperglycemia, and hypertension.[1] Several definitions have been proposed for the diagnosis of MetS. The most commonly used are those by the World Health Organization, the International Diabetes Federation (IDF), and the National Cholesterol Education Program–Adult Treatment Panel III. In our study, we applied new IDF criteria.[2]

It is estimated that around 20%–25% of the world's adult population have MetS[2] and they are twice likely to die from and three times likely to have heart attack or stroke.

A primary event in atherogenesis is endothelial dysfunction which occurs long before structural atherosclerotic changes and promotes cardiovascular events. Endothelial dysfunction is characterized by decreased nitric oxide (NO) bioavailability. NO is released from endothelial cells in response to shear stress and hormonal stimuli. NO may function as an endogenous antiatherogenic molecule by maintaining low arterial tone at rest, inhibiting leukocyte–endothelial interactions, platelet aggregation, and smooth muscle proliferation.[3],[4],[5]

Endothelial function can be assessed invasively or noninvasively. Invasive method is by intra-arterial infusion of acetylcholine in coronary or peripheral artery. Because of its invasive nature, this has been applied only in small studies and large epidemiological studies are lacking.[5],[6]

The assessment of endothelial function by flow-mediated vasodilatation (FMD) of the brachial artery has been proposed as a noninvasive surrogate marker for cardiovascular risk.[5],[6]

  Materials and Methods Top

Source of data

The study was conducted in patients attending the Medicine Department in Victoria Hospital and Bowring and Lady Curzon Hospital, Bengaluru, attached to Bangalore Medical College and Research Institute, Bengaluru.

Method of collection of data

  1. Study design: A case–control study
  2. Study period: November 2015–May 2017
  3. Place of study: Victoria Hospital and Bowring and Lady Curzon Hospital, Bengaluru
  4. Sample size: Fifty cases and fifty controls.

Inclusion criteria

  1. Patients above the age of 18 years
  2. Confirmed cases of MetS as per new IDF criteria
  3. Patients who give written and informed consent.

Exclusion criteria

  1. History of smoking
  2. History of alcohol
  3. Already on statin therapy
  4. Secondary hypertension
  5. Established CVDs
  6. Patients not giving written and informed consent.


  1. Detailed clinical history of the patients including age, sex, hypertension, diabetes mellitus (DM), heart diseases, smoking, and alcohol intake was taken
  2. Detailed clinical examination including pulse rate, blood pressure, height, weight, waist circumference (WC), and systemic examination with special emphasis on the cardiovascular system was done
  3. Blood investigation such as fasting blood glucose, lipid profile, and electrocardiogram was done
  4. FMD technique and subject preparation:[7]

The brachial artery was imaged above the antecubital fossa in the longitudinal plane. A segment with clear anterior and posterior intimal interfaces between the lumen and vessel wall was selected for continuous two-dimensional grayscale imaging. FMD technique relies on manual assessment of vessel diameters using visual inspection of single frames and placement of ultrasonic calipers at discrete points along the long axis of the B-mode image [Figure 1].[1]
Figure 1: Assessment of endothelial function in vivo using blood pressure cuff occlusion and release. On deflation of the cuff, an ultrasound probe monitor changes in diameter (a) and blood flow (b) of the brachial artery (c) Reproduced with permission of J.Vitta, MD

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After (baseline diameter), the right forearm is compressed by inflation of pneumatic tourniquet at suprasystolic pressure for 5 min. The diameter of the brachial artery is measured 60 s after the release of pressure. The diameter of the brachial artery is measured again 15 min after deflation of cuff to ensure that baseline has been reached.

Subject preparation

FMD can be influenced by dietary intake, recent aerobic exercise, caffeine and alcohol ingestion, and supplement/medication use. We assessed FMD when patients are fasted and have avoided exercise, caffeine, alcohol, drugs, stimulants, and medications for a consistent period of time (at least 6 h) to minimize the effect of these confounding factors.

Calculation of flow-mediated vasodilatation

FMD is calculated using the equation: FMD = (d 2 − d 1) × 100/d1, where d1 is the brachial artery diameter at baseline and d 2 is the brachial artery diameter 60 s after the release of pressure.[7],[8]

  Results and Analysis Top

A total number of 100 patients (50 cases and 50 controls) were taken for the study. The mean age was 49.76 ± 13.76 years among cases and 44.94 ± 16.09 years among controls. 54% are male and 46% are female in the study population.

In our study population, among the cases, 31 cases had fasting blood glucose (FBS) ≥100, 37 cases had triglycerides (TGs) >150, HDL was less in 39 cases (<40 in males and <50 in females), systolic blood pressure (SBP) >130 in 22 cases, and diastolic blood pressure (DBP) >85 in 17 cases, as shown in [Graph 1].

The mean FBS in cases was 170.56 ± 96.43 mg% and in controls 93.74 ± 11.53 mg%. The mean TG among the cases was 180.36 ± 59.75 mg/dl and among the controls 122.72 ± 25.99 mg/dl. The mean HDL among the cases was 33.6 ± 11.33 mg/dl and among the controls 47.23 ± 6.14 mg/dl. The mean SBP among the cases was 135.08 ± 12.35 mmHg and among the controls 124.52 ± 10.7 mmHg. The mean DBP among the cases was 83.48 ± 7.81 mmHg and among the controls 79.2 ± 7.13 mmHg. The mean WC among the cases was 91.02 ± 4.35 cm and among the controls 84.54 ± 4.37 cm [Table 1].
Table 1: Baseline characteristics of cases and controls

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The mean FMD% values in cases and controls were 7.24 ± 5.24 and 21.29 ± 9.29, respectively [Table 2].
Table 2: Mean FMD% among cases and controls

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A significant difference in FMD% between cases and controls was detected (P = 0.000).

Spearman's rho correlation analysis showed that there is a negative correlation between the number of components of MetS and FMD%, which is not statistically significant (−0.239).

  Discussion Top

MetS has received increased attention during the past few years because it is associated with an increased risk of type 2 DM, CVD, and premature mortality.[9] A large body of evidence has suggested that the presence of endothelial dysfunction represents a major promoter for atherosclerosis and thrombosis and is an independent prognostic predictor for the risk of future cardiovascular events in several groups of patients.[10],[11],[12] Flow-mediated dilatation can describe any vasodilatation of an artery following an increase in luminal blood flow and internal wall shear stress. Subsequent studies consolidated the link between increases in flow, wall shear stress, endothelial NO synthase expression, and NO bioactivity. The accumulated evidence strongly suggested that flow-associated shear was the physiological stimulus to endothelium-mediated vasodilation in vivo.[13],[14],[15],[16],[17],[18],[19] Endothelial dysfunction, as detected by FMD measurements in the brachial artery, has been shown to be an independent predictor of cardiovascular outcomes.[20],[21],[22],[23],[24],[25],[26]

In our study, the significant difference in FMD% between cases (7.24 ± 5.240) and controls (21.29 ± 9.29) is detected (P = 0.000). Pearson's correlation analysis showed negative correlations between FMD% and various variables.

Spearman's rho correlation analysis showed that there is a negative correlation between the number of components of MetS and FMD% (r = −0.239), which is not statistically significant.

Our study showed a significant difference in FMD% between cases and controls and is comparable to other studies such as Mannuva et al.[8] (mean FMD% values in cases and controls before statin treatment were 6.73% ± 2.55% and 11.03% ± 1.85%, respectively, P < 0.001), Hamburg et al.[27] also showed a significant difference in FMD% between patients with MetS and controls (2.84 ± 0.12% vs. 3.17% ± 0.08%, P = 0.0496). Melikian et al.[28] (patients with MetS had impaired endothelium-dependent vasodilatation [FMD%: −5.8 ± 0.4] compared to participants without MetS [FMD%: −7.9 ± 0.3] with P < 0.001).

Our study shows a negative correlation between the number of components of MetS and FMD%, which is not statistically significant. However, a study by Melikian et al. and Hamburg et al. showed a significant negative correlation between the number of components of MetS and FMD%.

However, the study of Indian population by Mannuva et al. did not show any significant negative correlation between the number of components of MetS and FMD%, which is similar to our study. Because the large prospective studies involving Indian population are lacking, it requires further studies to prove the relationship between the number of components of Mets and FMD.

The clinical application of FMD is currently limited by the lack of standardized protocols and reference values. Thus, FMD testing remains confined to research, where it is a valuable and important tool, mainly for the study of populations rather than individuals. The additive value of brachial ultrasound FMD over and above established traditional clinical tools remains to be proven, and ongoing studies are currently addressing this issue.

Limitations of the study

  1. Population included were small
  2. Other inflammatory markers such as high-sensitivity C-reactive protein assessment and endothelial NO estimation were not done.

  Conclusion Top

There is a significant difference in FMD% between MetS patients and controls as evidenced by the study. The clinical implications of FMD% require further studies.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Thijssen DH, van Bemmel MM, Bullens LM, Dawson EA, Hopkins ND, Tinken TM, et al. The impact of baseline diameter on flow-mediated dilation differs in young and older humans. Am J Physiol Heart Circ Physiol 2008;295:H1594-8.  Back to cited text no. 16
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Harris RA, Padilla J. Proper “normalization” of flow-mediated dilation for shear. J Appl Physiol (1985) 2007;103:1108.  Back to cited text no. 19
Laclaustra M, Frangi AF, Frangi AG, Casasnovas JA, Cia P. Association of endothelial function and vascular data with LDL-c and HDL-c in a homogeneous population of middle-aged, healthy military men: Evidence for a critical role of optimal lipid levels. Int J Cardiol 2008;125:376-82.  Back to cited text no. 20
Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO, et al. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol 2003;41:1769-75.  Back to cited text no. 21
Karatzis EN, Ikonomidis I, Vamvakou GD, Papaioannou TG, Protogerou AD, Andreadou I, et al. Long-term prognostic role of flow-mediated dilatation of the brachial artery after acute coronary syndromes without ST elevation. Am J Cardiol 2006;98:1424-8.  Back to cited text no. 22
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  [Figure 1]

  [Table 1], [Table 2]


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