Lifestyle factors and novel biomarkers in cardiometabolic diseases

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Socioeconomic factors, obesity, unhealthy diet, smoking and genetic factors are known as CVD risk factors. Metabolic syndrome (MetS) has been found to significantly increase the risk of CVDs. According to recent guidelines, promoting lifestyle interventions and weight management is essential. The measurement of novel biomarkers including fibroblast growth factor 21 (FGF21), lipocalin-2 (LCN-2), cystatin C, beta-2 microglobulin (B2M) and neurofilament light chain (NfL) may also provide valuable support for assessing CVDs and MetS.

Four studies in this thesis used the data from the Shenzhen-Hong Kong United Network on Cardiovascular Disease (SHUN-CVD), which is a population-based study conducted in China. The first study explored the relationship between hypertension and a healthy lifestyle score, which was derived from 5 factors: smoking, alcohol consumption, physical activity, body mass index and diet. The risk of hypertension tended to decrease with an increase in the healthy lifestyle score. Abdominal obesity is a risk factor for diabetes. The second study found that waist circumference (WC) had a significant linear relationship with haemoglobin A1c and fasting plasma glucose in both men and women. The optimal cutoff values of WC indicating a haemoglobin A1c of 6.5% in men and women are 85 cm and 86 cm, respectively.

Serum levels of FGF21, LCN-2, cystatin C and B2M were measured in the SHUN-CVD. The third study revealed that serum FGF21 was associated with systolic and diastolic blood pressure. A robust association was observed between FGF21 and hypertension. Additionally, CVDs are prevalent in patients with chronic kidney disease. The fourth study investigated the relationship between renal biomarkers and stroke risk. There were nearly a quarter (24%) of participants had high stroke risk. Serum LCN-2, cystatin C and B2M, independent of age, were associated with stroke risk.

MetS has been associated with neurological disorders and NfL is a neuro-axonal biomarker. The fifth study further examined the relationship between serum Nfl and MetS in US adults by using data from the National Health and Nutrition Examination Survey. The level of serum Nfl was increased in participants with MetS. NfL was significantly associated with both the number of MetS components and MetS severity score.

This thesis has several clinical implications. Firstly, there is an inverse relationship between the healthy lifestyle score and hypertension risk, which reinforces the need to address lifestyle to lower the risk of hypertension. Secondly, addressing abdominal obesity issue is beneficial to individuals with diabetes. WC cutoff values of 85 cm for men and 86 cm for women are appropriate for recommendation to undergo diabetes screening. Thirdly, FGF21 is a potential biomarker for assessing hypertension. Fourthly, serum LCN-2, cystatin C and B2M may be novel biomarkers for clinicians to assess stroke risk. Fifthly, measuring NfL may help identify neuro-axonal damage in patients with MetS and highlight the need for risk factor modification.