According to the International Diabetes Federation (IDF), between 20% and 25% of the world's adult population is living with MetS. As age increases, so does the prevalence of MetS, affecting >40% of individuals in their 60s. While MetS affects genders equally overall, it may be slightly higher in women than men.^1,3 

Individuals living with MetS are twice as likely to die from, and three times as likely to experience a myocardial infarction or stroke compared to those without the syndrome.³  

Furthermore, individuals with MetS have a ~5-fold increased risk of developing T2DM, adding to the burden of the >529 million people worldwide already living with T2DM in 2021.^3,4 

It should be noted that MetS does not only affect adults. A study showed that ~3% of children and ~5% of adolescents worldwide are affected by MetS. Its prevalence is slightly higher among children in low-income countries.¹ 

Definition of MetS 

According to the IDF definition, an individual is characterised as having MetS if they have central obesity (defined by waist circumference with ethnicity-specific values) plus any two of the following four factors (see Table 1 for MetS diagnostic criteria):^3,5 

1. High TG levels  
2. Low high density lipoprotein cholesterol (HDL-C) levels 
3. High blood pressure (BP) levels 
4. High fasting plasma glucose (FPG) levels.  

Pathophysiology of MetS 

The complex pathophysiology of MetS is poorly understood. The geographical distribution and rising prevalence in developing countries suggest that environmental and lifestyle factors, such as high-calorie diets and lack of physical activity, play a significant role.⁵  

Various hypotheses regarding the basic mechanisms of MetS include fatty acid flux, insulin resistance (IR), neurohormonal activation, low-grade chronic inflammation, and oxidative stress.⁵ 

Early intervention is key 

IR can lead to impaired glucose regulation and increased risks of T2DM as well as progression to atherosclerotic CVD - particularly due to post-prandial hyperglycaemic spikes that increase glucose levels significantly after meals. These spikes can lead to endothelial dysfunction, prothrombotic states, and chronic inflammation, all of which contribute to the development of CVDs. Studies have shown that individuals living with impaired glucose tolerance (IGT) or IFG are at an increased risk of CV events, even before the onset of diabetes.⁵ 

Hypertension is another critical component of MetS and a significant risk factor for all types of CVDs, including coronary artery disease, stroke, and renal failure. The prevalence of hypertension increases with age and is higher among individuals living with MetS. Effective management of BP is crucial to reducing the overall CV risk in these patients.⁵ 

Hyperdyslipidaemia in MetS is characterised by high TG and low HDL-C levels, both of which are associated with increased CV risk. Although low-density lipoprotein-cholesterol (LDL-C) reduction remains a primary treatment goal, addressing high TG levels and other lipid abnormalities is also essential for comprehensive CV risk management. Current treatments, including statins, aim to lower TG and improve HDL-C levels, thereby reducing the risk of CV events.⁵ 

Conclusion 

Addressing hyperdyslipidaemia, hypertension, and IR in MetS is vital for reducing the risk of CVD and T2DM. A comprehensive approach, including lifestyle changes and appropriate pharmacotherapy, is necessary to improve outcomes for individuals living with MetS. While lowering LDL-C is vital, addressing elevated TG and low HDL-C is also essential. Statins and other lipid-lowering treatments play a crucial role in reducing CV events. Effective BP management, often involving a combination of an ACE- inhibitor or ARB with a CCB or diuretic, is critical to reducing CV risk in individuals living with MetS. Early intervention in IR management is key to preventing diabetes and reducing CV risks. 

References 

1. Swarup S, Ahmed I, Grigorova Y, et al. Metabolic Syndrome. [Updated 2024 Mar 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459248/  
2. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and Management of the Metabolic Syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation, 2006. 
3. International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. 2023. [Internet]. Avialable at: https://idf.org/media/uploads/2023/05/attachments-30.pdf  
4. Ong KL, Stafford LK, McLaughlin SA, on behalf of the GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet, 2023. 
5. Jha BK, Sherpa ML, Imran M, et al. Progress in Understanding Metabolic Syndrome and Knowledge of Its Complex Pathophysiology. Diabetology, 2023. 
6. Dobrowolski P, Prejbisz A, Kuryłowicz A, et al. Metabolic syndrome - a new definition and management guidelines: A joint position paper by the Polish Society of Hypertension, Polish Society for the Treatment of Obesity, Polish Lipid Association, Polish Association for Study of Liver, Polish Society of Family Medicine, Polish Society of Lifestyle Medicine, Division of Prevention and Epidemiology Polish Cardiac Society, Club 30 Polish Cardiac Society, and Division of Metabolic and Bariatric Surgery Society of Polish Surgeons. Arch Med Sci, 2022.