Serum folate modified the association between low-density lipoprotein cholesterol and carotid intima-media thickness in Chinese hypertensive adults

Nutr Metab Cardiovasc Dis. 2020 Nov 27;30(12):2303-2311. doi: 10.1016/j.numecd.2020.07.021. Epub 2020 Jul 24.

Abstract

Background and aims: While folate is known for its importance in cardiovascular health, it is unknown whether folate status can modify the association between low-density lipoprotein cholesterol (LDL-C) and carotid intima-media thickness (CIMT). We aimed to investigate this question in a Chinese hypertensive population, who are at high-risk of low folate and atherosclerosis.

Methods and results: This report included 14,970 hypertensive adults (mean age 64.5 years; 40.3% male) from the China Stroke Primary Prevention Trial (CSPPT) and analyzed the fasting serum LDL-C and folate, and CIMT data obtained at the last follow-up visit. LDL-C was calculated using the Friedewald equation. Serum folate levels were measured by chemiluminescent immunoassay. CIMT was measured by ultrasound. Non-parametric smoothing plots, multivariate linear regression analysis, subgroup analyses and interaction testing were performed to examine the LDL-C-CIMI relationship and effect modification by folate. Consistent with graphic plots, multivariate linear regression showed that LDL-C levels were independently and positively associated with CIMT (β = 7.69, 95%CI: 5.76-9.62). More importantly, the relationship between LDL-C and CIMT was significantly attenuated with increasing serum folate levels (1st tertile: β = 10.06, 95%CI: 6.67-13.46; 2nd tertile: β = 6.81, 95%CI: 3.55-10.07; 3rd tertile: β = 5.96, 95%CI: 2.55-9.36; P-interaction = 0.045). Subgroup analyses showed the association between LDL-C and CIMT across serum folate tertiles was robust among various strata (all P-interaction >0.05).

Conclusions: Among Chinese hypertensive adults, the serum folate levels could modify the association between LDL-C and CIMT. Our findings, if further confirmed, have important clinical implications.

Keywords: Carotid intima-media thickness; Folate; Hypertension; Low-density lipoprotein cholesterol.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Pressure
  • Carotid Artery Diseases / blood*
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / epidemiology
  • Carotid Artery Diseases / physiopathology
  • Carotid Intima-Media Thickness*
  • China / epidemiology
  • Cholesterol, LDL / blood*
  • Cross-Sectional Studies
  • Female
  • Folic Acid / blood*
  • Humans
  • Hypertension / blood*
  • Hypertension / diagnosis
  • Hypertension / epidemiology
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors

Substances

  • Biomarkers
  • Cholesterol, LDL
  • Folic Acid