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Microvascular dysfunction and cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of death globally. Nevertheless, reliable tools to predict its onset and progression are lacking. The purpose of this research is to develop a method to identify and quantify microvascular dysfunction as an early marker of CVD that can be used in primary health care.

Background

Cardiovascular disease is the leading cause of death globally and although cardiovascular (CV) mortality has decreased over the last 10 years it remains a major threat to public health. It is well established that dysfunctional microcirculation, i.e. the smallest vessels in the body, is associated to CVD and CV complications. The microvessels play important roles in maintaining blood pressure and nutrient delivery to tissues and organs. By controlling vascular permeability, myogenic response and releasing various vasoactive substances such as nitric oxide, the microvessels can adapt blood flow according to local metabolic demands. Microvascular dysfunction may arise even before vascular pathologic changes manifest, but the causal relationship and the timing of the processes are not yet established.

In risk assessment for CVD, most CVD cases and deaths can be attributed to a number of modifiable risk factors such as hypertension and smoking. However, during the last two decades, population health and risk factor patterns for CV events have changed dramatically from focusing on high levels of cholesterol, blood pressure and smoking, to obesity, hypertriglyceridemia, and diabetes. Consequently, strategies for prevention of CVD based on traditional risk models developed a few decades ago start to lose relevance today. In addition, prevention strategies are primarily based on the likelihood of a CV event rather than complete assessment of an individual risk of developing a CV event. Measurement of microvascular function has the potential to improve risk prediction and clinical decision-making for prevention of CVD by providing an early and individual marker of vascular dysfunction. The skin is easily accessible for microcirculatory investigation and the developed method from this project will provide an inexpensive and easy measurement of microvascular function that can be used in primary health care.

Perimed has in collaboration with IMT, developed a pointwise fiberoptic based system for comprehensive microcirculation assessment, EPOS Enhanced Perfusion and Oxygen Saturation system. This system has been used to quantify microvascular function in 3809 individuals within the Swedish CardioPulmonary bioImage Study (SCAPIS). SCAPIS is a collaborative research project between six Swedish universities (Uppsala, Umeå, Linköping, Malmö/Lund, Gothenburg, and Stockholm). In total, SCAPIS has recruited 30,154 men and women aged 50 to 65 years with detailed imaging and functional analyses of the cardiovascular and pulmonary systems.

Aim of the project

The aim of this research project is to develop novel methods and mathematical models for studying microvascular function which will enable personalized information on the microvascular status for CV risk assessment.

We hypothesize that by using world unique data on the temporal dynamics of the microcirculation, along with data on the function of larger blood vessels, CV risk factors, and CV outcomes from registries, we will enhance our knowledge of how the microvascular function changes over time and how it relates to CVDs and CV risk.

The expected outcomes of this research are:

  1. novel mathematical models of skin microvascular function that can provide insights into the mechanisms of microvascular dysfunction and CVD
  2. new biomarkers of microvascular function that can improve CV risk stratification
  3. new strategies for prevention of CVD based on targeting the microcirculation.

About the project

Publications

Bergstrand, S., Jonasson H., Fredriksson I., Larsson M., Östgren, C.J. and Strömberg T. Association between cardiovascular risk profile and impaired microvascular function in a Swedish middle-aged cohort (the SCAPIS study). European Journal of Preventive Cardiology, Online ahead of print (2024). DOI: https://doi.org/10.1093/eurjpc/zwae052