The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease

Abstract

The Hordaland Homocysteine Study (HHS) is a population-based study of more than 18,000 men and women in the county of Hordaland in Western Norway. The first investigation (HHS-I) took place in 1992-93, when the subjects were aged 40-67 y. In 1997-99, a follow-up study (HHS-II) of 7,053 subjects was carried out. In this large population, plasma levels of total homocysteine (tHcy) are associated with several physiologic and lifestyle factors and common diseases. Increasing age, male sex, smoking, coffee consumption, high blood pressure, unfavorable lipid profile, high creatinine, and the MTHFR 677C > T polymorphism are among the factors associated with increased tHcy levels; physical activity, moderate alcohol consumption, and a good folate or vitamin B-12 status are associated with lower tHcy levels. Subjects with raised tHcy levels have increased risk of cardiovascular morbidity, cardiovascular and noncardiovascular mortality, and are more likely to suffer from depression and from cognitive deficit (elderly). Among women, raised tHcy levels are associated with decreased bone mineral density and increased risk of osteoporosis. Women with raised tHcy levels also have an increased risk of having suffered from pregnancy complications and an adverse pregnancy outcome. Significant associations between tHcy and clinical outcomes are usually observed for tHcy levels > 15 micromol/L, but for most conditions, there is a continuous concentration-response relation with no apparent threshold concentration. Overall, the findings from HHS indicate that a raised tHcy level is associated with multiple clinical conditions, whereas a low tHcy level is associated with better physical and mental health.

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

“…The community‐based HUSK (Hordaland Health Study) has been described in detail elsewhere13, 14 (http://husk.b.uib.no). The present study cohort was confined to 7050 men and women who were born during 1925‐1927 or 1950‐1951 and participated in the baseline examinations in the period of April 1998 to June 1999.…”

A simplified method for the determination of total homocysteine in plasma by electrospray tandem mass spectrometry

“…Homocysteine has gained interest for its implication in the pathogenesis of cardiovascular diseases (atherosclerosis, thromboembolism and heart disease) and for the association with other clinical conditions (depression, complications of pregnancy, Alzheimer and osteoporosis) [1,2].…”

Evidence for sex differences in the determinants of homocysteine concentrations

“…A high homocysteine phenotype accompanied by low folate is associated with increased risk of several major human pathologies including cardiovascular disease [1,2], birth defects such as spina bifida [3] and cleft palate [4], and other complications of pregnancy including spontaneous abortion, pre-eclampsia, prematurity and low birth weight [5]. Folate is required for nucleic acid biosynthesis and the methylation of lipids, hormones, DNA and proteins, while homocysteine is a key intermediate in the methylation cycle [5] and may itself be teratogenic [6,7].…”

“…Recognition that mild hyperhomocysteinemia is a cardiovascular risk factor/marker [1,2] has prompted considerable research into understanding the biochemical, environmental and genetic influences that have an impact on homocysteine concentrations. The variables known to be significantly associated with homocysteine levels include: vitamin status, in particular folate, riboflavin and vitamin B 12 ; age; sex; lifestyle, in particular smoking status; prescription drugs; renal function; and genetics, in particular the well-established influence of the 677C>T polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene [11].…”