HDL cholesterol protective role questioned

2nd December 2022

Increased HDL cholesterol is considered protective against CVD but a study in Black and White individuals has re-examined this role

HDL cholesterol is generally considered to be protective against coronary heart disease (CHD) but a recent analysis that included both Black and White patients suggests that higher levels offer no protection in either race with an elevated CHD risk due to low levels only relevant for White individuals.

Globally, coronary heart diseases were estimated to kill 17.9 million people in 2019, which represents 32% of all global deaths, with 85% of deaths due to heart attack and stroke. Since the early 1970’s, there has been a well-established and inverse relationship between plasma high-density lipoprotein (HDL) cholesterol and CHD risk. However, whether this relationship remains for different ethnicities is uncertain. It is known for example, that after accounting for social determinants of health and other risk factors, Black patients have a similar risk of a fatal CHD to White patients, but that the risk for a nonfatal CHD is consistently lower for Black people. The underlying reasons behind this difference are unclear and have been further confounded by the somewhat paradoxical observation that low levels of HDL cholesterol are associated with a reduced risk of incident CHD in black participants.

In trying to better understand the relationship between HDL cholesterol and incident CHD, a team of US researchers turned to data collected in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, designed to examine underlying racial and regional differences in stroke and mortality. The researchers selected a cohort without baseline CHD and for whom a wide range of clinical and demographic factors were collected. The cohort was followed over time and the number of incident CHD (i.e., definite or probable nonfatal myocardial infarction or CHD death) were recorded.

HDL cholesterol and CHD events in Black and White patients

A total of 23,901 participants with a mean age of 64.1 years (58.3% female) and of whom, 57.7% self-identified as White were included in the analysis and followed for a median of 10.7 years. During the follow-up there were 1,615 CHD events of which 41.1% occurred in Black participants and 45.5% in women.

When analysing the relationship between CHD events and plasma LDL cholesterol in fully adjusted models, for every 1 standard deviation increase in LDL levels, there was a modest increase in CHD risk (Hazard ratio, HR = 1.10, 95% CI 1.05 – 1.17). Similarly, for triglyceride levels, there was also a modest increase in CHD risk (HR = 1.05, 95% CI 1.01 – 1.10). However, in fully adjusted models, there was a non-significant association between HDL cholesterol (HDL-C) levels and CHD risk (HR = 0.95, 95% CI 0.89 – 1.02).

But when researchers examined the relationship between HDL-C and CHD risk stratified by race, they found something unusual. As might be expected based on the currently known relationship, a low HDL-C level was associated with an increased risk of CHD, but this was only significant for White patients (HR = 1.22, 95% CI 1.05 – 1.43). Among Black patients the relationship was not significant (HR = 0.94, 95% CI 0.78 – 1.14). Furthermore, a high HDL-C level was not protective in either White (HR = 0.96, 95% CI 0.79 – 1.16) or Black (HR = 0.91, 95% CI 0.74 – 1.12) patients.

Based on these findings, the authors concluded that current high-density lipoprotein cholesterol–based risk calculations could lead to inaccurate risk assessment in Black adults.

Citation
Zakai NA et al. Race-Dependent Association of High-Density Lipoprotein Cholesterol Levels With Incident Coronary Artery Disease. J Am Coll Cardiol 2022

Screening older black patients identifies elevated incidence of precursor condition for multiple myeloma

16th December 2021

Screening older black patients or those with relatives who have blood cancer identified an elevated precursor incidence for multiple myeloma

The screening of older black patients or those with a first-degree relative who has a haematological cancer led to the detection of monoclonal gammopathy of undetermined significance (MGUS), which is a precursor to multiple myeloma (MM). This was the conclusion of a study by a researchers from the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, US, presented at ASH 2021.

MGUS a benign condition which is usually diagnosed incidentally when tests are performed to investigate other problems although MGUS is a precursor to multiple myeloma in around 1% of cases. However, the prevalence of MGUS has not been described in a population at high risk of developing MM, in particular, Black/African American (AA) individuals or first-degree relatives of patients with haematologic malignancies (HM).

In 2019, the US researchers launched the first nationwide US (PROMISE) screening older black patients study for individuals at high risk of MM to help better identify what population would benefit most from screening and early intervention for precursor MM stages. The overarching aim of the study is to assess the prevalence of MGUS in a high risk population and to characterise the clinical variables of individuals who screen positive. For the present study, the researchers reported on screening data available for the first 2960 participants.

The researcher team recruited individuals aged 40 or older with an additional MM risk factor which included Black/AAs and those with a first-degree relative diagnosed with a haematologic malignancy or a precursor condition to MM. Blood from all participants was analysed to measure the serum free light chains (sFLC), IgG, IgA and IgM. In addition and for comparative purposes, the team also identified and screened additional individuals from the Mass General Brigham (MGB) Biobank who met the PROMISE enrolment criteria. The researchers measured Heavy-Chain MGUS (HC-MGUS) as a marker for MGUS.

Findings

Screening older black patients occurred with 2960 individuals participants (1092 from PROMISE). The overall prevalence of HC-MGUS was 9.6% (95% CI 8.6 – 11%) and 10% (95% CI 8.3-12%) in PROMISE and 9.4% (95% CI 8.1 – 11%) in the MGB cohort.

The prevalence of HC-MGUS increased with age in high-risk individuals from 4.9% (CI 3.3 – 6.9%) for participants aged 40-49 to 13% (95% CI 10 – 17%) in the 70-79 range (P < 0.005 ). Among monoclonal HC-MGUS, they detected 65% IgG, 18% IgM, and 18% IgA. M-spike was quantified in 97% of samples.

The authors concluded that screening older black patients or those who have a first-degree relative with an HM have a high prevalence MGUS and may therefore benefit from precision screening approaches to allow for early detection and clinical intervention.

Citation

El-Khoury H et al. High Prevalence of Monoclonal Gammopathy in a Population at Risk: The First Results of the Promise Study. ASH Conference 2021