Cardiac markers & extended lipid profile as risk stratification tool

*Dr Barnali Das talks about biomarker based cardiac care model and emphasises that laboratories must take on the responsibility of being the evidence based decision makers in healthcare ecosystem managing the essential diagnostics like cardiac care and chronic conditions affecting population health or acute care

29^th September, 2023 is World Heart Day. The biomarker based cardiac care model in clinical decision making involves strategies for harmonising, communicating and integrating with all stakeholders; like, clinicians and diagnosticians, in order to formulate guidelines for assisting in correct measurement, diagnosis and management of cardiovascular diseases. Laboratories must take on the responsibility of being the evidence based decision makers in healthcare ecosystem managing the essential diagnostics like cardiac care and chronic conditions affecting population health or acute care. We must drive the care-models on measurable outcome and risk stratification/ risk assessment.

Risk stratification in apparently healthy adults for developing future cardiovascular diseases would be paramount. Directing these individuals with appropriate preventive interventions along with closer follow-up could prevent their progression to a higher risk group.

NT-proBNP is indicated for the diagnosis of individuals suspected of having congestive heart failure and detection of mild forms of cardiac dysfunction. It also aids in the assessment of heart failure severity in patients diagnosed with congestive heart failure. It is further indicated for the risk stratification of patients with acute coronary syndrome and congestive heart failure, and it can also be used for monitoring the treatment in patients with left ventricular dysfunction. It can help in the cardiovascular risk assessment of patients with type 2 diabetes mellitus. It can be used to identify elderly individuals at high-risk for atrial fibrillation. For patients at risk of developing HF, natriuretic peptide biomarker-based screening followed by team-based care, including a cardiovascular specialist optimising GDMT, can be useful to prevent the development of left ventricular dysfunction (systolic or diastolic) or new-onset HF. ADA Consensus 2022 on Heart Failure in Diabetes provides clear guidance to practitioners on the best approaches for screening and diagnosing HF in individuals with diabetes or prediabetes.

Cut-off values

In patients acutely presenting with signs and symptoms of cardiac disease, the values of > 300 pg/mL indicate that acute heart failure is likely. The age stratified values are to be considered by clinician as well. In chronic setting, acute heart failure is likely if the values are ≥ 125 pg/mL. In patients of type 2 diabetes mellitus without signs and symptoms of cardiac disease, values of ≥ 125 pg/mL are predictive of the occurrence of subsequent cardiovascular events.

The addition of a high sensitive troponin (hsTn) assay to current risk-stratification tools like hsCRP, lipid -profile can enhance risk prediction in case of CVD and over-all cardiovascular deaths in asymptomatic individual thereby alerting clinicians in order to prevent future CVDs. The evaluation of high sensitive Troponin assay in comparison to existing risk stratification algorithms and biomarkers also show promising results wherein there is improvement in the prognostic accuracy. High sensitive troponin I assay can function as predictive biomarkers for cardiovascular risk stratification (high/ moderate/ low risk) in the general population. The following cut-off points may be used to aid in stratifying the risk of cardiovascular disease in asymptomatic individuals in conjunction with clinical findings:

We have done a small pilot study of hsTnI as risk stratification tool, along with hsCRP and lipid profile to predict cardiovascular risk in the general population.

Cardiovascular disease has been projected as the leading cause of death globally and it would account for more than 23 million deaths per year by 2030. In India, death rate due to cardiovascular diseases showed to have a 41% increase, whereas in Europe & United States it has declined significantly. Cardiovascular diseases (CVD) still remains the primary cause of death worldwide as well as in India regardless of advances in diagnosis, treatment and risk assessment tools. Chest pain is one of the most common reasons for people visiting the accident and emergency department (A&E) in hospitals to rule out and rule in acute coronary syndrome (ACS). CVD has significant morbidity and mortality if not treated in a timely manner.

The evaluation of patients with chest pain requires highly skilled resources and expensive time.  Reducing patient length of stay with safe outcomes maximises care while also reducing overall costs. Early and accurate diagnosis of acute myocardial infarction is essential for successful treatment and improved outcomes.

Troponin measurement, a keystone in the diagnosis and management of ACS, detects the levels of troponin – a cardiac-specific structural protein released by damaged heart muscles. High sensitive Troponin assay help in higher analytic precision at lower concentrations, and increased clinical sensitivity for acute coronary syndrome (ACS). It can detect even small changes in troponin concentration (delta changes: increase or decrease) in particular time frame.

Sex differences are common across multiple aspects of cardiovascular care including diagnosis, treatment, and outcomes. Recognising that poorer outcomes for women vs. men post-intervention may result from delayed diagnosis of women, and with full appreciation that some men may be more aggressively treated based on use of lower upper reference limits that lack sex discrimination, the Biochemistry & Immunology team at Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute (KDAH) sought to investigate the opportunity to move from an overall URL (Upper reference limit) to sex-specific URLs consistent with guideline-based care.

However, there were concerns raised about the use of single, universal cut-off value of hsTroponin I for both men and women, as there is a potential risk of under-diagnosis in women, since they have a lower threshold value of troponin. A total of 2797 female patients and 2805 male patients were enrolled. The difference in females undetected without gender specific cut-off was 14 per cent. The cut-off threshold value of hsTnI for male was decided to be 34 pg/ml. Implementation of gender-specific diagnostic threshold helped in identifying more women at increased risk of ACS or death, than a generic threshold.

Therefore, implementation of sex-specific upper reference limits identified an additional 14 per cent of at risk women with potential acute myocardial infarction. This in turn also decreased the number of men being diagnosed by 3 per cent.

As a primary target, Lipid Association of India in 2016 recommended a LDL-Cholesterol level of <50mg/dl and a Non HDL-Cholesterol (co primary target) level of <80mg/dl for patients of Very High Risk group (VHRG) which includes patients of atherosclerotic Cardiovascular Disease (ASCVD). LDL-C and Non HDL-C Target for High Risk group are <70 mg/dl and <100 mg/dl respectively. LDL-C and Non HDL-C Target for Moderate and Low Risk groups are <100 mg/dl and <130 mg/dl respectively (reference LAIECS-1 in 2016). Non HDL-Cholesterol depicts cholesterol content of all atherogenic lipoproteins. When we subtract HDL-Cholesterol from Total Cholesterol, we get the value of Non HDL – Cholesterol.  New extreme risk groups (ERG) with category A and B have been introduced in the LAIECS-3 in 2020. Non fasting lipid profile is preferred. Furthermore, National Lipid Association of US in their recent scientific statement published in March 2021 also recommended strict LDL-C goal for extreme risk group for prevention of ASCVD in South Asians in the US.

Furthermore, we (Das, B., Daga, M.K. and Gupta, S.K.), evaluated the role of non-conventional lipid risk factors like Lipoprotein(a) [Lp(a)], Apolipoprotein A-I (Apo A-I) and Apolipoprotein B-100 (Apo B-100) and other conventional lipid profile parameters: total cholesterol, triglycerides, HDL-C and LDL-C.

We have studied in children and adolescents of premature coronary artery disease (CAD) patients in India; and thereby explain the highest occurrence of premature CAD in this population.

Since Apo B-100/Apo A-I ratio is better than the LDL-C/HDL-C ratio, we have defined a new index (Lipid Pentad Index, LPI) incorporating this ratio into the known Lipid Tetrad Index. Thus, in the present work, we define,

• LPI = [TC x TG x Lp(a) x Apo B-100] /Apo A-I

LPI reflected the total burden arising out of alteration in traditional lipid profile as well as emerging lipid risk factors like Lp(a), Apo A-I and Apo B-100.

Therefore, cardiac biomarkers and extended lipid profile can provide key insights into patients with cardiovascular disease (CVD), contributing to patient screening, risk assessment, risk stratification, admission, monitoring, treatment guide, as well as prognostication.

About author:

Dr Barnali Das is MD, DNB, PGDHHM, FAACC, Lead Consultant, Biochemistry & immunology, Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute, Mumbai, India, Executive Member, Scientific Division, International Federation of Clinical Chemistry& Laboratory Medicine (IFCC) and Chair, Association for Diagnostics & Laboratory Medicine (formerly AACC) India Section