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Author: Tracy
Using a national, population-based prospective cohort of the China Health Assessment and Risk Reduction through National Teamwork (ChinaHEART) project, the team aimed to compare China's LDL-C profile with that of other Western countries and to determine the association between LDL-C concentrations and mortality in populations with different ASCVD risks. In addition, the team further explored this association in different subgroups based on age, gender, and comorbidity status, particularly diabetes. In addition, the team further explored this association in different subgroups based on age, gender, and comorbidity status, particularly diabetes.
On July 18, 2024, Chen Liang's team from the Department of Cardiac Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, published a research paper entitled "Low-Density Lipoprotein Cholesterol, Cardiovascular Disease Risk, and Mortality in China" in the journal JAMA. This study found that the association between LDL-C and mortality varied across different ASCVD risk cohorts, suggesting that individuals at higher risk of ASCVD and patients with diabetes may require more stringent lipid control goals.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2821340?resultClick=1
Background:
01
Low-density lipoprotein cholesterol (LDL-C) is considered one of the major risk factors for cardiovascular disease because of its causal relationship with atherosclerotic cardiovascular disease (ASCVD). It is estimated that HDL-C levels cause up to 4.3 million deaths each year, accounting for 7.7% of global deaths. Therefore, LDL-C has been strongly demonstrated as a therapeutic target in randomized clinical trials. Lipid-lowering therapies, particularly statins, have been widely used as an essential clinical strategy for the primary and secondary prevention of ASCVD.
The U-shaped association between LDL-C concentrations and all-cause or cardiovascular disease (CVD) mortality has recently been well defined in the general population in developed countries. Still, this association remains unclear in individuals from developing countries and in populations with different ASCVD risk stratifications. The different associations between LDL-C and mortality in individuals with different ASCVD risks can determine the different lipid management strategies used in clinical practice, which are relevant to billions of people. The original prevention of cardiovascular disease has been promoted worldwide, and lipid management is one of the important aspects of this strategy. However, in clinical practice, the association between LDL-C and mortality in people at low risk of ASCVD is unclear. The lower the better, the strategy of lipid-lowering therapy for patients with ASCVD, requires more support. In addition, research on dyslipidemia and the management of comorbidities such as diabetes and hypertension remains insufficient.
In this study, the team utilized a national, population-based prospective cohort of the China Health Assessment and Risk Reduction through National Teamwork (ChinaHEART) project to compare the LDL-C profile in China with that of other Western countries and to determine the association between LDL-C concentrations and mortality in populations with different ASCVD risks. In addition, the team further explored this association in different subgroups based on age, gender, and comorbidity status, particularly diabetes.
Research Progress
02
LDL-C and total population mortality
At a median follow-up of 4.6 (3.1-5.8) years, 92,888 participants (2.45%) died, including 44,977 (1.58%) in the low-risk cohort, 41,217 (4.97%) in the primary prevention cohort, and 6,694 (5.53%) in the secondary prevention cohort. The causes of death varied across the three cohorts, with cardiovascular disease (38,627 deaths) and cancer being the most common causes. Cardiovascular mortality was 0.54% (15,331 participants) in the low-risk group, 2.33% (19,341 participants) in the primary prevention group, and 3.27% (3,955 participants) in the secondary prevention group.
The association between LDL-C levels and the risk of all-cause cardiovascular mortality in both the low-risk and primary prevention groups was U-shaped; In the secondary prevention group, it was J-shaped. In the secondary prevention cohort, for all-cause mortality, the 95% CI included an HR of 1.0 at LDL-C concentrations below 70 mg/dL, which increased significantly with increasing LDL-C. The association trend between LDL-C and CVD mortality was consistent with that of all-cause mortality.
Regarding the association between LDL-C and cause-specific mortality, there was a U-shaped association between LDL-C and stroke, and between LDL-C and ischemic heart disease, in low-risk and primary prevention cohorts. In addition, there was a monotonically increasing association in the secondary prevention cohort. The high ASCVD risk cohort had lower lowest RCS curves for stroke (128.9 mg/dL versus 108.3 mg/dL versus 65 mg/dL) and ischemic heart disease mortality (113.3 mg/dL versus 89.9 mg/dL versus 50.7 mg/dL) compared with the low-risk cohort. For lung cancer, the 95% CI was 1.0 at any concentration of LDL-C.
Association between low-density lipoprotein cholesterol (LDL-C) and all-cause, cardiovascular disease (CVD), and cancer mortality.
LDL-C和死亡率（按分层）
LDL-C levels corresponding to the lowest CVD mortality in RCS were 117.8 mg/dL in the low-risk cohort, 106.0 mg/dL in the primary prevention cohort, and 55.8 mg/dL in the secondary prevention cohort, suggesting that a reduction in low LDL-C targets and an increased risk of ASCVD should be considered to reduce CVD mortality. The trend of association between LDL-C and all-cause mortality in the secondary prevention cohort was different between male and female individuals. Similarly, in the secondary prevention cohort, high LDL-C levels were associated with an increased risk of all-cause or CVD mortality in male individuals, while this association was not detected in women.
In the low-risk cohort, LDL-C was associated with all-cause mortality, with CVD mortality differing between individuals over 60 years of age and those over 60 years of age. All-cause mortality (HR, 1.68; 95% CI, 1.59-1.78) was higher in older adults (HR, 1.41; 95% CI, 1.32-1.52) in the lowest LDL-C group (LDL-C<40 mg/dL) than in middle-aged adults (HR, 1.41; 95% CI, 1.32-1.52). Nonetheless, all-cause mortality (HR, 1.07; 95% CI, 0.96-1.20) was lower in older adults (HR) than in middleage (HR) in the highest LDL-C group (LDL-C>190 mg/dL). ，1.65；95%CI，1.46-1.87）。
The association between LDL-C and mortality was consistent with the overall population in participants with or without hypertension. LDL-C concentrations associated with the lowest all-cause mortality (90.9 mg/dL vs 117.0 mg/dL) and CVD mortality (87.0 mg/dL vs 114.6 mg/dL) were lower than those in non-diabetic patients across the cohort. The interaction between LDL-C level and diabetes status, all-cause mortality and CVD mortality was significant in the ASCVD risk cohort (P interaction <.05). Diabetic patients with LDL-C concentrations greater than 160 mg/dL had a higher risk of all-cause and CVD mortality than non-diabetic patients in all ASCVD risk stratifications. These findings suggest that diabetes is a non-negligible risk factor for all individuals, regardless of their risk of ASCVD.
Association between low-density lipoprotein cholesterol (LDL-C) and cause-specific mortality.
Conclusions of the study
03
This study is the first study to evaluate the association of LDL-C with mortality in different ASCVD risk populations, based on a study of 4.4 million people in a prospective cohort of the general population nationwide in China. The overall LDL-C level of the entire Chinese cohort is lower than that of Western countries; However, the total mortality rate of cardiovascular diseases in China is higher than that in Western countries.
In this study, the association between LDL-C concentrations and mortality varied in populations at risk of stratification of ASCVD. Both LDL-C levels and high levels were associated with increased cardiovascular disease in both low-risk and primary prevention cohorts, and LDL-C levels associated with the lowest mortality in these populations were lower than in Western populations. For the secondary prevention cohort, very low LDL-C levels were not associated with increased mortality. This study demonstrates that lipid-lowering therapy is urgently needed not only in traditional primary and secondary prevention settings, but also in individuals at low risk of ASCVD. Patients with diabetes mellitus in low-risk, primary and secondary prevention populations should receive more frequent lipid monitoring and lipid lowering.
Resources:
1.Knuuti J, Wijns W, Saraste A, et al; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020; 41(3):407-477.
2.Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019; 140(11):e596-e646.
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