Dr Ala’a Alkerwi from the LIH Department of Population Health contributed to a global public health study on cholesterol, which was published in Nature in June 2020. The paper brings forward a major global repositioning of lipid-related risk over the past four decades. Specifically, non-optimal cholesterol trends shifted from being a distinct feature of high-income western countries to being a significant burden in low- and middle-income nations. The study, led by Imperial College London, was conducted in the framework of the international Non-Communicable Diseases Risk Factor Collaboration (NCD-RisC). Luxembourg contributed with data generated from the national population-based study “ORISCAV-LUX” (Observation des Risques et de la Santé Cardiovasculaire au Luxembourg), which had been conducted in 2007-2008 on more than 1,400 residents with the aim of assessing cardiovascular health and risk factors in Luxembourg.

Cholesterol plays a role in the formation and functioning of cell membranes. Specifically, high-density lipoprotein (HDL), i.e. ‘good’ cholesterol, may have a protective effect against heart attack and stroke by mopping up non-HDL ‘bad’ cholesterol. Excess in the latter, the levels of which should not exceed 2mmol/L, can cause a build-up in the blood vessels, thereby blocking blood supply and leading to ischaemic heart disease (IHD) and ischaemic stroke. High blood cholesterol has typically been regarded as a feature of wealthy western countries. However, dietary and behavioural determinants of blood cholesterol, as well as the adoption of lipid-lowering medications such as statins, have been evolving throughout the world in the last decades. These changes have significantly altered the levels of HDL and non-HDL cholesterol worldwide, possibly with diverging geographical patterns. However, no global study had previously reported or quantified the trends in HDL and non-HDL cholesterol levels over time.     

A shift in the global cholesterol epicentre

To address this gap, this study analysed 1,127 population-based studies that measured blood lipids in 102.6 million adults, in order to estimate trends in total, non-HDL and HDL cholesterol levels for 200 countries from 1980 to 2018. The researchers found that there was little change in total and non-HDL cholesterol from 1980 to 2018 at the global level. Total cholesterol in 2018 was 4.6 mmol l⁻¹ for women and 4.5 mmol l⁻¹ for men, having decreased by a marginal 0.03 mmol l⁻¹ per decade in women and 0.05 mmol l⁻¹ per decade in men. However, at the regional level, total cholesterol decreased by a significant 0.3 mmol l⁻¹ per decade in high-income western countries and in Central and Eastern Europe, where it had been the highest in 1980, largely due to a decline in non-HDL cholesterol. Conversely, it rose by more than 0.1 mmol l⁻¹ per decade in East and Southeast Asia due to an increase in non-HDL cholesterol.

Indeed, a similar trend was observed with non-HDL cholesterol, which remained globally unchanged due to the net effects of a substantial decline in high-income Western regions and Central and Eastern Europe — with north-western Europe recording the largest drop at >0.3 mmol l⁻¹ per decade — coupled with a rise in East and Southeast Asia (0.2 mmol l⁻¹ per decade), parts of sub-Saharan Africa and Melanesia. As a result of these diverging patterns, European countries that had the highest levels of non-HDL cholesterol in 1980 (>4.5 mmol l⁻¹ in women and >4.7 mmol l⁻¹ in men), such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta, have been replaced by nations in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand, where non-HDL cholesterol increased by as much as 0.23 mmol l⁻¹ per decade. These findings reverse the view that high cholesterol is a feature of higher-income countries.  

A focus on Luxembourg

In line with the trends identified by the study, Luxembourg experienced an improvement in the cholesterol status of its population. Indeed, the Grand Duchy ranks among the top 10 countries with the largest rates of decline between 1980 and 2018, for both men and women. Moreover, in 2018, it boasted the fourth lowest level of non-HDL cholesterol for women among European countries.

Implications for cardiovascular health and mortality

The researchers also estimated the number of deaths by IHD and ischaemic stroke attributable to high levels of non-HDL cholesterol. They found that, in 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million worldwide deaths from IHD and ischaemic stroke, accounting for a third of all deaths from these conditions. Furthermore, this number was found to have increased by around 910,000 between 1990 and 2017 globally, as the net result of an almost 50% drop in western countries and a large increase throughout Asia. Indeed, the number of deaths attributable to high non-HDL cholesterol more than tripled in East Asia and more than doubled in Southeast Asia. As a result, these regions accounted for half of all deaths attributable to high non-HDL cholesterol by 2017, compared with a quarter in 1990.

Diet and medication as the main contributing factors

Diet and cholesterol-lowering medication are the two main factors explaining the observed trends. The decrease in non-HDL cholesterol in western countries was found to have started already in the 1980s, before the widespread use of statins. This indicates that changes in dietary habits and the reduction in saturated and trans fats could have been the main determinant of this decline. However, the growing use of statins after the late 1990s is thought to have contributed to up to one half of the decrease in higher-income countries where statin use is more common. In parallel, the consumption of animal fats and processed foods has increased substantially in East and Southeast Asia, where statins are not yet widely used, explaining the documented rise in non-HDL levels.

“This international study shows that, when looking at non-HDL cholesterol, low- and middle-income countries have emerged as the new global epicentre of non-optimal cholesterol, suggesting that lipid-related disorders are actually an important public health challenge even in these regions"

says Dr Ala'a Alkerwi. 

"Nevertheless, further lowering non-HDL cholesterol would indeed be beneficial even in higher-income countries. Population-based policies to improve diets and provide better healthcare are therefore urgently needed in all countries”, she concludes.

The study was published in June 2020 in the prestigious journal Nature, with the full title “Repositioning of the global epicentre of non-optimal cholesterol”. It was funded by the Wellcome Trust (Biomedical Resource & Multi-User Equipment grant 01506/Z/13/Z) and by the British Heart Foundation (Centre of Research Excellence grant RE/18/4/34215).