Cardiovascular Risk in Metabolic Syndrome

Metabolic syndrome significantly increases the risk of cardiovascular events in both younger and older individuals.

A meta-analysis published in 2010, including approximately one million participants from 87 studies, demonstrated that patients with metabolic syndrome had a 2.35-fold increased risk of developing cardiovascular disease (45,251 participants). The risk of cardiovascular mortality was increased 2.40-fold (67,365 participants), while the risk of all-cause mortality was increased 1.50-fold (90,788 participants).

Furthermore, individuals with metabolic syndrome exhibited a twofold increased risk of myocardial infarction (17,918 participants) and a 2.27-fold increased risk of stroke (90,166 participants).

Thus, the doubling of cardiovascular disease risk affects a substantial number of individuals. Consequently, interventions aimed at reducing cardiovascular risk are clinically justified and strongly recommended.

Other meta-analyses have reported similar findings, and the association between metabolic syndrome and increased cardiovascular risk is now widely accepted.

Cardiovascular Risk Factors

Cholesterol

Evidence from observational studies, genetic studies, and intervention trials has established low-density lipoprotein cholesterol (LDL-C) as the principal causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Other atherogenic lipoproteins also contribute to disease development.

The most important characteristics of LDL-C as a cardiovascular risk factor are:

  • The longer LDL-C levels remain reduced, the lower the risk of cardiovascular events.
  • The relative reduction in cardiovascular risk is proportional to the magnitude of LDL-C reduction.
  • This benefit is independent of the therapeutic strategy used to lower LDL-C.
  • In patients at high cardiovascular risk, a reduction of LDL-C by at least 50% is recommended.
  • Even when this target is not fully achieved, lipid-lowering therapy should be continued, as modest reductions in LDL-C may still prevent future cardiovascular events.

Non-high-density lipoprotein cholesterol (non-HDL-C) includes all lipoproteins associated with increased ASCVD risk. It is calculated as total cholesterol minus HDL cholesterol.

Both very low and very high HDL-C concentrations have been associated with increased cardiovascular risk. To date, clinical studies have not demonstrated that pharmacologically increasing HDL-C levels reduces ASCVD risk.

Hypertension

Hypertension is a major risk factor for ASCVD and non-atherosclerotic cardiovascular diseases, particularly heart failure. It is also associated with an increased risk of chronic kidney disease, peripheral arterial disease, and atrial fibrillation.

The risk of death from cardiovascular disease or stroke increases approximately linearly when diastolic blood pressure exceeds 90 mmHg.

Smoking

Lifelong cigarette smoking reduces average life expectancy by approximately ten years.

Approximately 50% of preventable deaths attributable to smoking are caused by cardiovascular disease, and about half of these cardiovascular deaths result from ASCVD.

Women appear to be more susceptible to the harmful cardiovascular effects of smoking than men.

Diabetes Mellitus

Type 1 diabetes, type 2 diabetes, and prediabetes are independent risk factors for ASCVD and approximately double cardiovascular risk.

Women with type 2 diabetes have a particularly increased risk of stroke.

Therefore, lipid-lowering therapy and LDL-C reduction based on cardiovascular risk stratification represent essential components of diabetes management.

The treatment targets recommended by the German Diabetes Association are derived from the cardiovascular risk assessment models and treatment guidelines published by the European Society of Cardiology (ESC 2021 and ESC 2023).

Obesity

Body mass index (BMI) has increased steadily worldwide over recent decades.

Among non-smokers, mortality increases linearly with BMI. In smokers, the relationship follows a J-shaped curve, with mortality increasing at BMI values below 25 kg/m².

The lowest mortality rates are observed at BMI values between 20 and 25 kg/m².

Both BMI and waist circumference are independently associated with an increased risk of ASCVD and type 2 diabetes mellitus.

References

  1. Mottillo Salvatore, Filion KB, Genest J, et al. (2010). The metabolic syndrome and cardiovascular risk: A systematic review and meta-analysis. Journal of the American College of Cardiology, 56(14), 1113–1132.
  2. European Society of Cardiology (2021). 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. European Heart Journal, 42(34), 3227–3337.
  3. European Society of Cardiology (2023). ESC Guidelines for the Management of Dyslipidaemias and Cardiovascular Risk Reduction. European Heart Journal.
  4. Brian Ference et al. (2017). Low-density lipoproteins cause atherosclerotic cardiovascular disease. European Heart Journal, 38(32), 2459–2472.
  5. Baigent Colin et al. (2010). Efficacy and safety of more intensive lowering of LDL cholesterol. The Lancet, 376(9753), 1670–1681.
  6. Joseph P. S. Perk et al. (2012). European Guidelines on cardiovascular disease prevention in clinical practice. European Heart Journal, 33(13), 1635–1701.
  7. World Health Organization (2023). WHO Report on the Global Tobacco Epidemic. Geneva: WHO.
  8. Emerging Risk Factors Collaboration (2010). Diabetes mellitus, fasting glucose, and risk of vascular disease. The Lancet, 375(9733), 2215–2222.
  9. Prospective Studies Collaboration (2009). Body-mass index and cause-specific mortality in 900,000 adults. The Lancet, 373(9669), 1083–1096.
  10. German Diabetes Association (2023). Evidence-based recommendations for cardiovascular risk management in diabetes mellitus. Berlin: DDG.
  11. Khan Supriya S. et al. (2018). Association of HDL cholesterol with cardiovascular disease and mortality. Journal of the American College of Cardiology, 71(5), 471–482.