Heart Disease, Coronary

Do and colleagues¹⁶ (link) performed a two-sample MR analysis to evaluate the causal effect of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides on coronary heart disease (CHD) risk, using a total of 185 genetics variants. Summary association results were obtained from the Global Lipids Genetics Consortium¹⁷ (link) and the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Consortium,¹⁸ (link) and were downloaded from Do and colleagues’ supplementary material (standard errors were estimated based on the regression coefficients and P-values). Genetic variants were classified as instruments for each lipid fraction using a statistical criterion (P < 1 × 10⁻⁸), resulting in 73 instruments for LDL-C, 85 for HDL-C and 31 for triglycerides.
White and colleagues¹⁹ (link) performed a similar analysis, but with plasma urate levels rather than lipid fractions. 31 variants associated with urate levels (P < 5 × 10⁻⁷) were used as genetic instruments, and the required summary statistics were obtained from the GWAS catalogue [https://www.ebi.ac.uk/gwas/].

Two separate Markov decision models were developed to compare the long-term costs and health benefits of the IraPEN program (primary CVD prevention) with the status quo (no prevention) in two distinct scenarios. In the base case scenario, individuals without diabetes were included, while patients with diabetes were included in the alternative scenario. Each Markov model has four health states with transitions between the states according to age, sex, and the CVD risk characteristics of participants (Figure 1). In contrast to the usual Markov models, which are structured based on cohorts with average profiles, we decided to categorize the individuals based on their CVD risks. As the intervention (treatment) varied according to CVD risk level, it is logical to model them separately. In this way, we can take into account their specific characteristics. Therefore, based on WHO/ISH CVD risk prediction charts for EMR B, four index cohorts were constructed (5 ). These hypothetical cohorts were used as a representative for individuals with low, moderate, high, and very high CVD risk profiles. The CVD risk state represents the starting point for all people who are 40 years old. It was assumed that people in this state may either remain in the same health state, move to the stroke state, or CHD (coronary heart disease) state, or die. As long as they are event-free, these individuals can stay in a healthy state, but after the first event, they move to the CHD or stroke state and stay there until their death.
In WHO/ISH CVD risk prediction charts, the CVD risk is calculated based on individuals' age and risk factors such as blood pressure, lipid profile, diabetes, and smoking status and categorized into the following five groups: below 10% (low-risk group), between 10 and 19% (moderate-risk group), between 20 and 29% (high-risk group), between 30 and 39%, and above 40% (very high-risk group). As the individuals in the two latter groups are treated the same, in the IraPEN program, whoever has a CVD risk above 30% is categorized as the very high-risk group.
Therefore, considering what was mentioned earlier, all the Iranians aged older than 40 years who did not have CHD or stroke events before were eligible for this program. According to the recent census (2016), 31.16% of Iranians were older than 40 years (6 ). By adding individuals aged older than 30 years with the aforementioned risk factors, we can conclude that this program is going to screen at least 25 million people yearly.
The healthcare perspective and a 40-year time horizon were adopted for this analysis. As the analysis is a comparison between IraPEN (intervention) and status quo (no intervention) which both have the same Markov structure and transition probabilities, it is not expected that half cycle correction (HCC) approach makes any difference in ICER results; therefore, HCC was not applied to this analysis (7 (link)).
The hypothetical cohorts were used as a representative for individuals with low, moderate, high, and very high CVD risk profiles (Table 1). Progressively, a proportion of the cohort can go to the CHD state, who are the survivors of the first CHD event, or to the stroke state who are the survivors of the first stroke event. Those CHD and stroke events that were fatal moved to the death state. In general, the people in these two states are at a higher risk of dying from CHD or stroke, but they may die from any other causes like the normal population. Table 2 summarizes the assumptions of this analysis.

In this study, we used participants from the previously published “APAC” cohort, a subpopulation of the Kailuan study. The APAC exclusion criteria were previous reported history of stroke, transient ischemic attack, and coronary disease at baseline and absence of neurologic deficits for stroke.
In this study, we further excluded subjects with a previously reported HF or AF. One hundred eighty subjects were excluded because of lack of information or a history of CVD. Finally, 5260 participants were included to develop and validate the sex‐specific physical activity equations (PA equations) (the detailed flow chart can be found in Figure 1).
A baseline examination was conducted at the time of study inclusion. Basic demographic variables such as information of lifestyle and education as well as the past medical history were collected with standardized questionnaires. Body weight and height were measured, and body mass index was calculated as kilograms per meters squared. Information on smoking, drinking, and physical activity were also collected by questionnaires. SBP and DBP were taken at a 5‐min interval, values were measured twice and the mean of the SBPs and DBPs was respectively used.
Physical activity was recorded by using the standardized IPAQ short form under the assistance of professional researchers. The subjects were asked about the time and frequencies of exercises. We then divided the physical activity into low‐intensity activity (<10 min/week), moderate‐activity (10–80 min/week), and high‐intensity activity (>80 min/week). The first follow‐up was conducted between 2011 and 2012. Individuals were followed up every 2 years through face‐to‐face interviews. Subjects with a history of CVD diseases, including MI, chronic ischemic (CI) HF, cerebral hemorrhage (CH), and stroke were excluded.

The participants in this study were ≥18 years old and agreed to participate in follow‐up from Jidong community, Caifeidian District, Tangshan city in Hebei province in China.²³ The participants were followed up once every other year from 2011 to 2019, a relatively long time span. The Kailuan group is China's large coal mining enterprises, which includes 101,510 employees and retirees. The study cohort of this work was selected from APAC study with 5440 participants. The APAC study is a subpopulation of the Kailuan cohort, which were obtained by adopting stratified random sampling based on age and sex according to the 2010 China National Population Census, the main inclusion criteria for APAC study were no history of stroke, coronary disease and transient ischemic attack.