This retrospective cohort study involved 1013 patients aged 18–44 years who were hospitalized for their first occurrence of CHD. Data were collected from the cardiology department at Beijing Anzhen Hospital between October 2022 and October 2023. Patients with secondary diagnoses of prior CHD, previous percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), post-acute myocardial infarction (AMI) syndrome, chronic ischemic heart disease, heart failure (before or after CHD diagnosis), arteritis, congenital heart disease, and cancer, as well as those without specific information at the time of their first CHD diagnosis and those with a history of CHD 3 months prior were excluded.

The study protocol was reviewed and approved by the Ethics Committee of Beijing Anzhen Hospital. Written informed consent was obtained from all participants prior to their inclusion in the study.

Baseline information was collected from the hospital’s electronic medical records and other medical documents by trained abstractors. Collected demographic information included sex and age, while exposure to risk factors was assessed, including obesity, medical history of hypertension and diabetes, LDL-C levels, and smoking habits. Data on secondary prevention therapies, such as the use of aspirin, $\beta$-blockers, angiotensin receptor blockers/angiotensin-converting enzyme inhibitors (ARB/ACEI), and lipid-lowering therapy, were also gathered. Biochemical indicators recorded included hemoglobin A1c (HbA1c), triglycerides (TG), total cholesterol (TC), LDL-C, and high-density lipoprotein cholesterol (HDL-C). Coronary angiographic findings were reviewed to document the presence of occlusion or stenosis in the native coronary arteries (including the left main, left anterior descending, circumflex, and right coronary arteries). Follow-up information was collected through face-to-face interviews, which included changes in smoking habits, newly diagnosed hypertension and diabetes, secondary MI events, secondary preventive therapy, and coronary revascularization. For biochemical indicators, data from the last 3 months were recorded, or blood samples were collected and measured. Anthropometric data, such as height, weight, and blood pressure, were measured following standard procedures in the clinics.

Hypertension and diabetes were defined based on documented histories in medical records. Body mass index (BMI) was calculated as weight (kg) divided by the square of height (m²), with obesity defined as BMI $\ge$28 kg/m². Smokers were defined as those who reported smoking $>$100 cigarettes or for $>$6 months, with a cessation time of 6 months. The optimal target for LDL-C was set at 1.8 mmol/L. Baseline LDL-C levels were categorized into two groups: 1.8 mmol/L and $\ge$1.8 mmol/L. The last LDL-C measurements were categorized into four groups: 1.4 mmol/L, 1.4–1.79 mmol/L, 1.8–2.59 mmol/L, and $\ge$2.6 mmol/L. The degree of LDL-C reduction was calculated as the difference between LDL-C levels at the end of the study and at baseline divided by the LDL-C levels at baseline. This reduction was categorized into four groups: 0%, 0%–29.9%, 30%–49.9%, and $\ge$50%. A trajectory model was used to determine the temporal development of LDL-C levels: LDL-C-uncontrolled ($\ge$1.8 mmol/L at both baseline and end of the study), LDL-C-worsened (LDL-C 1.8 mmol/L at baseline and $\ge$1.8 mmol/L at the end), LDL-C-improved (LDL-C $\ge$1.8 mmol/L at baseline and 1.8 mmol/L at the end), and LDL-C-controlled (LDL-C 1.8 mmol/L at both baseline and end). Coronary artery disease was defined as the presence of significant stenosis ($\ge$50%) in the main coronary arteries, as confirmed by coronary angiography, including the left main coronary artery (LM), left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA). Single vessel lesion was defined as a stenosis of $\ge$50% in the LAD, LCX, or RCA. Multi-vessel disease is defined as a stenosis of $\ge$50% in two or three of these vessels (LAD, LCX, and RCA) or $\ge$50% in the LM.

The primary endpoint was secondary MI events. MI was defined according to established criteria [19], which included both ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI), with information obtained from relevant hospital records.

Categorical variables were expressed as counts and percentages, with differences in groups compared using chi-square tests or Fisher’s exact tests when any expected cell count was 5. Continuous variables with normal distributions were presented as mean $\pm$ standard deviation, while those with skewed distributions were presented as median (interquartile range). Student’s t-test was used to compare two independent samples for normally distributed continuous variables, and the Mann-Whitney U-test was used for continuous variables with skewed distributions. Kaplan-Meier survival analysis was utilized to compare the impact of baseline LDL-C levels on MI events, with the log-rank method employed to test for significant differences between groups. Logistic regression models were utilized to examine the relationships between the extent of LDL-C reduction, pattern of LDL-C changes, and last recorded LDL-C level with MI events. These models calculated crude and adjusted odds ratios (ORs) along with corresponding 95% confidence intervals (95% CIs). All reported p-values were two-sided, with p 0.05 considered statistically significant. Statistical analysis was conducted using IBM SPSS Statistics version 25.0 (IBM, Armonk, NY, USA).

Our study included 1013 patients, with a mean age of 38.5 $\pm$ 10.8 years at the time of CHD diagnosis. The majority of participants were male (94.7%). Among these patients, 547 (54.0%) presented with multi-vessel disease, 786 (77.6%) underwent PCI, 155 (15.3%) were managed solely with medication, and 72 (7.1%) underwent CABG.

At baseline, the prevalence rates of hypertension (48.0% vs. 55.0%) and diabetes (19.6% vs. 26.7%) were lower than those at the end of the study. Conversely, the prevalence rates of smoking (75.1% vs. 36.2%) and obesity (37.9% vs. 34.2%) were higher at baseline. Among the patients who smoked at baseline, 51.8% (394 of 761) quit smoking during the study period. Significant improvements were observed in the mean levels of HbA1c, diastolic blood pressure (DBP), TC, LDL-C, HDL-C, non-HDL-C, and TG at the end of the study (all p 0.05). Specifically, the mean LDL-C decreased from 2.83 $\pm$ 1.10 mmol/L to 2.28 $\pm$ 0.93 mmol/L, while the mean non-HDL-C decreased from 2.59 $\pm$ 1.10 mmol/L to 1.98 $\pm$ 1.07 mmol/L. A high percentage of patients received secondary preventive therapy, particularly by the end of the study. At baseline, 88.4% of patients were prescribed a statin, 8.5% were taking ezetimibe, and none were on a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. By the end of the study, these percentages increased to 91.2%, 36.2%, and 3.8%, respectively (Table 1).

Lipid levels, including LDL-C, non-HDL-C, HDL-C, and TG, were assessed at various time points following discharge (Table 2). Compared with baseline, all lipid indicators showed significant improvements. The percentage of patients achieving ideal targets for LDL-C, non-HDL-C, and TG peaked in the first year post-discharge, followed by a subsequent decline (p 0.05). In contrast, no significant differences in HDL-C levels were observed across the different years following discharge (p = 0.169). Initially, 4.6% of patients had LDL-C levels 1.4 mmol/L, while 13.6% had levels 1.8 mmol/L. These percentages increased to 17.2% and 37.8%, respectively, within the first year, before slightly decreasing to 12.5% and 28.6%, respectively, 3 years later.

At the study’s outset, 138 of 1013 individuals achieved the ideal LDL-C target of 1.8 mmol/L. By the end of the study, the proportion of individuals meeting this target significantly increased: 71.7% of those with baseline LDL-C 1.8 mmol/L compared with 28.1% of those with LDL-C $\ge$1.8 mmol/L at baseline (p 0.001). The patterns of LDL-C changes were categorized as follows: LDL-C-uncontrolled (62.1%), LDL-C-worsen (3.8%), LDL-C-improved (24.3%), and LDL-C-controlled (9.8%).

We calculated the difference between baseline LDL-C and the endpoint levels, revealing the distribution of LDL-C reductions: 26.9% of patients experienced an increase in LDL-C (reduction 0%), 39.6% had a reduction of 0%–29.9%, 23.9% had a reduction of 30%–49.9%, and 9.6% had a reduction of $\ge$50%.

During a median follow-up period of 1.7 years (interquartile range: 1.0–3.0 years), 96 new cases of MI were identified. The crude rates of MI events over time were as follows: 1-year MI rate: 2.1%, 3-year rate: 5.8%, 5-year rate: 8.2%, and $\ge$8-year rate: 9.7% (Fig. 1).

Fig. 1.

Distribution of myocardial infarction (MI) events during a median follow-up period of 1.7 years.

Kaplan-Meier survival analysis curves (Fig. 2) illustrated the cumulative incidence of MI events in two groups, based on a baseline LDL-C threshold of 1.8 mmol/L. The group with LDL-C levels 1.8 mmol/L exhibited a slightly lower cumulative incidence of MI events than those with LDL-C levels $\ge$1.8 mmol/L. However, this difference did not reach statistical significance (log-rank p = 0.335).

Fig. 2.

Kaplan-Meier survival analysis curves for myocardial infarction (MI) events. LDL-C, low-density lipoprotein cholesterol.

Univariate Cox regression analysis indicated no significant association between baseline LDL-C levels and the risk of MI occurrence (HR = 0.99, 95% CI: 0.84–1.17). After adjusting for age, sex, history of AMI, three-vessel disease, and treatment measures (Model 2), as well as for hypertension, diabetes, smoking status, HDL-C, TG, and BMI (Model 3), LDL-C levels remained insignificantly associated with MI risk (all p $>$ 0.05). Sensitivity analyses using categorical variables showed that LDL-C levels 1.8 mmol/L did not significantly reduce the risk of MI compared with LDL-C levels $\ge$1.8 mmol/L, regardless of confounding adjustments (Table 3).

We analyzed the relationship between the pattern of LDL-C changes and the risk of MI events, using LDL-C-uncontrolled as the reference group. Both univariate and multivariate analyses failed to demonstrate a significant correlation between the trajectory of LDL-C changes (including LDL-C-worsen, LDL-C-improved, and LDL-C-controlled) and the occurrence of MI events (Table 4).

We also compared the risk of MI based on the degree of LDL-C level reduction, using a reduction of 0–29.9% as the reference group. The findings indicated that reductions of 30–49.9% or $\ge$50% were not associated with a decreased risk of MI events (Table 4).

Additionally, we examined the association between LDL-C levels at the last recorded measurement and MI risk, with LDL-C $\ge$2.6 mmol/L as the reference group. Results showed that individuals with LDL-C 1.4 mmol/L had a significantly decreased risk of MI events, with a crude OR of 0.45 (95% CI: 0.27–0.75) and an adjusted OR of 0.57 (95% CI: 0.33–0.98). However, no significant reductions in MI risk were observed among individuals with LDL-C levels of 1.8–2.59 mmol/L and 1.4–1.79 mmol/L (Table 4).