This study aims to conduct a 10-year follow-up to assess ASCVD risk in Pakistan among individuals aged 30 years and above without a known history of ASCVD. The focus will be on evaluating ASCVD risk over this specific 10-year timeframe. The study will also validate risk assessment scores for identifying high-risk individuals and examine the incidence rate of ASCVD events during long-term follow-up.

Cardiovascular diseases (CVD) pose a formidable challenge as the leading cause of premature mortality globally, affecting diverse populations across income societies. The dynamic interplay of sex and age significantly influences the trajectory and prognosis of atherosclerotic cardiovascular diseases (ASCVD). Previously perceived as an ailment predominantly afflicting affluent older men, ASCVD has undergone a transformative shift, emerging as an epidemic impacting the productivity of both young men and women. This resonance is particularly pronounced in communities with varying economic backgrounds, including high-income and low-to-middle-income settings. The far-reaching consequences of premature CVD extend beyond the individual, exerting socioeconomic strains on families and societies, especially in lower-income communities. Recognizing the gravity of this situation, the World Health Organization (WHO) initiated the "25 by 25" campaign, aiming to curtail premature mortality from non-communicable diseases, with over 60% attributed to CVD, by 25% before 2025.

While global data on gender- and age-specific variations in CVD risk factors and outcomes have been extensively documented, the local evidence in Pakistan underscores a crucial research gap. A contemporary ST-elevation acute coronary syndrome (STE-ACS) cohort in Pakistan reveals a noteworthy 12% of premature cases (<40 years). A study by Ullah W et al., comprising 15,106 participants from the Cardiac Registry of Pakistan Catheterization Percutaneous Coronary Intervention, reports 7.4% of patients under 40 years. However, comprehensive local evidence on the incidence of ASCVD among the young population remains scarce.

Current risk assessment guidelines, exemplified by the 2019 ACC/AHA Cardiovascular Risk Assessment Guidelines, predominantly employ race- and sex-specific Pooled Cohort Equations (PCE) for predicting 10-year CVD risk, specifically in adults aged 40 to 75. However, these guidelines need more direct applicability to young adults, who often exhibit a paradox of low 10-year ASCVD predicted risk despite harboring a high lifetime risk profile. Acknowledging this discrepancy, the 2018 AHA/ACC cholesterol guideline advocates for estimating lifetime or 30-year ASCVD risk for individuals under 40.

Transitioning from risk assessment to lipid modulation, mainly focusing on low-density lipoproteins (LDL), unveils a pivotal role in atherogenesis. LDL assumes primary responsibility in cholesterol transport. The strategic modulation of lipid profiles has emerged as a central goal for cardiovascular prevention, concentrated on mitigating cardiovascular risk through targeted reduction of LDL-cholesterol using diverse lipid-lowering agents. Recent attention has shifted towards compounds offering nuanced insights into pro-atherogenic risk, with apolipoproteins playing an essential role in regulating lipoprotein metabolism and garnering significant attention in atherosclerosis.

Among the various apolipoproteins, apolipoprotein B (Apo B) emerges as a crucial component integral to all atherogenic lipids, including very low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs), LDLs, and chylomicrons. Existing literature underscores substantial variability in the lipid composition of Apo B lipoproteins, positioning Apo B as superior to total cholesterol and triglyceride levels in predicting cardiovascular risk. However, the predictive role of Apo B versus LDL-cholesterol remains controversial. While some studies advocate for Apo B as a more precise predictor of cardiovascular risk than LDL-cholesterol and non-high-density lipoprotein cholesterol (non-HDL), a recent extensive study involving over 300,000 patients did not establish the superiority of Apo B over LDL-cholesterol in assessing cardiovascular risk. This divergence in findings is mirrored in the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice. Consequently, a series of comprehensive studies is imperative to delineate the precise role of Apo B as a predictor of cardiovascular diseases (CVDs).

In light of Pakistan's escalating ASCVD burden, early identification and optimal management of modifiable risk factors become imperative for prevention. While conclusive studies are lacking, expert recommendations underscore the utility of "total/absolute CVD risk" assessment in guiding management decisions. This study, utilizing the ASCVD risk score and WHO risk score system, aims to evaluate ASCVD risk in young individuals, categorizing risks into low, intermediate, and high groups to guide tailored interventions, be it lifestyle modifications, non-pharmaceutical management, or pharmaceutical interventions, at each specific stage.

Inclusion Criteria:

• Individuals of any gender
• Individuals aged 30 years and above
• The study ensured a diverse representation to encompass a broad spectrum of experiences and risk factors within this age group
• Individuals without pre-existing cardiovascular conditions

Exclusion Criteria:

• Individuals with a confirmed diagnosis of ASCVD
• Confirmed cases of cancer
• participants who express a refusal to provide informed consent

The sample size, determined by insights from a study by An J, which showcased a median 10-year ASCVD risk of 0.6% in a sizable sample of 414,260 young adults, has been rigorously calculated. To enhance the robustness of our study and account for potential observational bias and missing clinical characteristics, the initially identified sample size has been increased by a factor of 1.5. This adjustment ensures a more comprehensive representation, resulting in a final sample size of 3,513 individuals, specifically young and healthy participants. To accurately reflect the diverse population across Pakistan, stratification based on the 2017 census data will be employed, ensuring representation from all four provinces and optimizing the study's applicability and generalizability.