Previous epidemiological studies have reported that elevated Lp(a) levels were the remarkable independent risk factor for premature coronary heart disease (PCHD)1–5.The PROCAM Study reported that Lp(a) as a risk factor for premature myocardial infarction, and the age of premature events was less than 45years3, 4. The GRIP Study reported that evaluated Lp(a) levels substantially increases cardiovascular risks in men aged 40–59 years4. However,rare available measures were used to reduced Lp(a) levels effectively. In this retrospective study, we indicated that PCHD patients showed higher Lp(a) levels than health controls, and the Lp(a) levels increased PCHD risk remarkably, the results was similar with previously study1–5.
Nevertheless, there was no standardized Lp(a) measurement in terms of heterogeneity of Lp(a) particle sizes9, 24, 25. Several epidemiological, Mendelian randomization and genome-wide association studies reported that elevated Lp(a) (≥ 50 mg/dl) is an independent and significant risk factor for CHD26–28. However, this recommendation neglects patients with Lp(a) level 25–50 mg/dl2.The risk of Calcificaortic valve stenosis (CAVS)was defined as high Lp(a) > 40 to 60 mg/dl2. The German and U.K. apheresis guidelines recommended Lp(a) > 60 mg/dl to specially treat who has elevated Lp(a) level and recurrent CVD events, or uncontrollable elevated LDL-C11.A large meta-analysis collected 126,634 participants and 1.3 million person-years of follow-up, showing that Lp(a) > 30 mg/dl increased myocardial infarction risk1. The 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia recommended Lp(a) ≥ 30 mg/dl as a risk factor for CHD7, 8.In our study, we defined Lp(a) ≥ 30 mg/dl as elevated Lp(a). Elevated Lp(a) subgroup had more PCHD patients than normal Lp(a) subgroup, which was consistent with the results of previous research.
Diet, exercise and the majority of lipid lowering drugs rarely change Lp(a) levels4. Of note, a meta-analysis reported that statin reduced LDL-C levels by 39% without changing Lp(a) levels12. In a PCSK9 Phase II conducted trial, the Lp(a) did not substantially reduced in any dosing groups13.10 mg Ezetimibe remarkably reduced plasma Lp(a) levels when compared with placebo29. In amipomersen Phase III trials, the mean percent Lp(a) levels decreased at 28 weeks was substantially more than placebo group, but it had more side effects, such as injection site reactions, hepatic steatosis and hepatic enzyme elevation9. Research reported that CETP inhibitors reduced the mean Lp(a) levels by 25–40%in a larger Phase II or Phase III clinical trial9, 30, 31.Other studies showed Lp(a) levels association with daily intake of vitamin D or monounsaturated fatty acids, but no correlation with lifestyle9. Smoking cessation was shown to reduce or increase Lp(a) concentrations32. Recent genome-wide association studies showed that LPA SNP rs10455872 was significantly associated with elevated Lp(a) levels11. However, some individuals have alleles that not express elevated Lp(a)11, 32.Therefore, several therapies have been shown to reduce Lp(a) levels, but none of them was widely used clinically9.
Currently, HRQOL can effectively improve the elevated Lp(a) levels was hardly known. Coronary heart disease has poorer HRQOL than that of healthy controls 15, 16. It was also found that mental disorders increased PCHD risk5, 21.Psychological interventions had effect on mortality and cardiovascular morbidity33, 34,while HRQOL can notably decrease Lp(a) levels is still unknown. Our study discovered that mental health can significantly decrease Lp(a) levels and PCHD risk in elevated Lp(a) subgroup, while was not correlated with normal elevated Lp(a) subgroup. Therefore, we suggested that better mental health is a promising protective factor for elevated Lp(a) levels. Previously, the association between BMI and Lp(a) levels is controversial35. BMI was not correlated with Lp(a) levels in the Women's Health Study36, while it was correlated with 20–29 years young adults in the Cherokee Diabetes Study37 and obese South Indian men35, 38.Our finding suggested that PCHD patients significantly high BMI than health controls in elevated Lp(a) group. Moreover, Exercise does not significantly reduce Lp(a) levels4, 9.Our study indicated that physical functioning and role-physical limitation did not effectively decrease Lp(a). Herein, we suggested that Lp(a) levels was not able to be lower by only doing exercise. In our study, PCHD patients high ApoA1 levels than health controls in total Lp(a)group. Some studies reported that Lp(a) is made up of apoA covalently bound to ApoB-1009, 11. IONIS-Apo(a)Rx antisense oligonucleotide selectively reduced the synthesis of apoA in the liver and consequently the plasma concentration of Lp(a) in Phase I study9. We suggested that decreased apoA levels were another novel therapy for elevated Lp(a) levels.
Other risk factors, such as smoking, hypertension, diabetes and dyslipidemia were the independent risk factors for PCHD1, 2, 4, 5, our finding was consistent with previous studies. A German’s study reported that 61%current smokers, approximately 40%active smokers in young and mid-aged German adults, increases premature MI significantly. In the DEGS1 survey, 40% of young and 16% mid-aged German population have hypertension, while other studies showed that the proportion of arterial hypertension was 70% in German4. Hypertriglyceridemia was the most important risk factor for young myocardial infarction39. However, triglycerides did not increase PCHD risk in our study, the result was consistent with previous research4, and uric acid had no difference between PCHD group and health control group, which is consistent with before40, we considered different regions and eating habits.