BACKGROUND:

Little data exist on the clinical features of patients with an extremely low level of high-density lipoprotein (HDL) cholesterol (<20 mg/dL).

OBJECTIVE:

To assess the clinical characteristics of Japanese patients with extremely low HDL cholesterol levels.

METHODS:

In this observational study of 429 patients with extremely low HDL cholesterol levels among 43,368 subjects whose HDL cholesterol was measured for any reason at Kanazawa University Hospital from April 2004 to March 2014, we investigated the presence of coronary artery disease, chronic kidney disease, the potential causes of reduced HDL cholesterol, their prognosis, and the cause of death.

RESULTS:

Most patients (n = 425, 99%) exhibited secondary causes, including malignancies (n = 157, 37%), inflammatory diseases (n = 219, 51%), or other critical situations, such as major bleeding (n = 58, 14%). During the median 175-day follow-up period, 106 patients died. The causes of death in 80 (75%) patients were malignancies, inflammatory diseases, or major bleeding, in contrast to a relatively low incidence of death from atherosclerotic cardiovascular disease (n = 10, 10%). Multiple regression analysis showed that the presence of malignancy and HDL cholesterol was independently associated with death, in addition to age. The cumulative survival curve revealed that patients with an HDL cholesterol of <15 mg/dl, determined using the receiver-operating characteristic curve, had significantly higher mortality than those whose HDL cholesterol level was ≥15 mg/dL.

CONCLUSIONS:

Extremely low HDL cholesterol levels could be a useful marker for poor prognosis, not necessarily related to cardiovascular diseases.

PURPOSE OF REVIEW:

To describe recent findings regarding the role of rare and common genetic variants in atrial fibrillation.

RECENT FINDINGS:

Atrial fibrillation is associated with several clinical risk factors and

its development is affected by genetic background. To date, rare variants from more than 30 genes have been identified from studies of familial cases or individuals with lone atrial fibrillation. In addition to using the candidate gene approach for the identification of rare variants, next-generation sequencing approaches such as genomic, whole exome and targeted sequencing have been employed. Furthermore, evidence of association between common variants and atrial fibrillation has been discovered through genome-wide association studies. Although the power of any one single-nucleotide polymorphism (SNP) associated with atrial fibrillation is weak, a genetic risk score comprising 12 SNPs may identify individuals at an increased risk for atrial fibrillation. This SNP panel may also delineate genotypes to enable stratification of atrial fibrillation ablation therapy or periinterventional management.

SUMMARY:

Although studies have demonstrated that atrial fibrillation is highly heritable, many aspects of atrial fibrillation remain unknown. Rigorous research efforts continue with the expectation that the contribution of variants and candidate genes that contribute to the overall genetic architecture of atrial fibrillation will be identified and characterized in the coming years.