Consider reclassification factors

In addition to the variables included in the Aus CVD risk calculator, clinicians should consider other ‘reclassification factors’ that may help refine CVD risk categorisation.

Reclassification factors have been identified based on which factors are likely to improve risk estimation beyond traditional CVD risk prediction equations including:

• ethnicity
• family history of premature CVD
• chronic kidney disease
• severe mental illness
• coronary artery calcium score

Reclassification factors are of most value when the person’s risk lies close to a risk threshold, as a small shift in risk estimate may result in their risk being categorised in a different risk category.

Table 6: Reclassification factors and effect on risk estimates

1. Family history of premature CVD is defined as coronary heart disease (CHD) or stroke in a first-degree female relative aged <65 years or a first-degree male relative aged <55 years.
2. Severe mental illness is defined in this guideline as a current or recent mental health condition requiring specialist treatment, whether received or not, in the 5 years prior to the CVD risk assessment. Derived from PREDICT cohort.⁵⁰

Reclassification factors were selected based on evidence reviews that sought to identify risk factors that increased or decreased estimated CVD risk beyond traditional risk calculators, not merely because they are independent risk factors for CVD.

Ethnicity

The following recommendations were derived from the available evidence and do not represent a complete list of ethnicities in a multicultural Australian society.

General considerations

First Nations people have an elevated risk of developing, and dying from, CVD.³⁶,³⁷

There are currently no empirical data to examine the accuracy of the Aus CVD risk calculator when applied to First Nations people. Given the underestimation of CVD risk using existing algorithms, it is difficult to state with confidence the likely impact of modified algorithms and additional CVD risk factors incorporated into the Aus CVD risk calculator until data on the new algorithm are available.

In Australian healthcare, there is no standard or accepted practice for collecting data on ethnicity among non-Indigenous people or for classifying non-Indigenous populations into broad ethnic groups. Ethnicity can be self-reported.

Evidence for associations between ethnicity and CVD risk level is, therefore, of moderate certainty, due to the limited application of available data to Australian populations

The Aus CVD risk calculator has a separate equation for people with diabetes (noting that it is not validated for people with type 1 diabetes and may give an inaccurate risk estimate in these people). The Aus CVD risk calculator also considers socioeconomic disadvantage (see Socioeconomic factors for context), which may help improve risk prediction for First Nations people and potentially people from other groups and communities.

Practice points

• Irrespective of their country of birth or appearance, ask everyone: “Do you [does the person] identify as being of Aboriginal and /or Torres Strait Islander origin?”.
• When reclassifying risk, it is important to account for the presence of kidney disease risk factors and a severe mental illness among First Nations people; these conditions are more common among the First Nations communities and therefore the person’s estimated CVD risk may require reclassification to a higher risk category.

Support for the recommendations

A large New Zealand cohort study of 400,000 adults without known CVD found that, compared with people of European ethnicity, and adjusting for other PREDICT CVD risk factors, the 5-year risk of a major cardiovascular event was higher in self-reported Māori (men: 48%; women: 34% higher), Pacific Islanders (men: 18%; women: 22% higher), and people of Indian ethnicity (men: 34%; women: 13% higher).¹ In contrast, the 5-year risk of a major cardiovascular event was lower in people of Chinese or other East Asian ethnicity (men: 33%; women: 25% lower).¹

Family history

People with a family history of premature CVD – defined as coronary heart disease (CHD) or stroke in a first-degree female relative aged <65 years or a first-degree male relative aged <55 years – are at increased risk of developing CVD.³⁸

Although family history of premature CVD has a strong relationship to CVD as a single variable (hazard ratios of 1.59 [95% CI 1.56 to 1.63)] in women and 1.73 [95% CI 1.70 to 1.76] in men),³⁹ this is largely accounted for by other risk factors in the Aus CVD risk calculator.

However, data are conflicting on whether family history adds additional discrimination value when variables are pooled by using traditional CVD risk calculators. For example, it did not add discrimination value to the American College of Cardiology/American Heart Association Pooled Cohort Equation.⁴⁰

Based on data from the PREDICT cohort, estimating CVD risk using traditional CVD risk factors (i.e. age, smoking status, diabetes, blood pressure, cholesterol level, socioeconomic status) plus a family history of premature CVD or stroke (as defined above), modestly improves CVD risk estimation in men, but not in women, compared with estimating CVD risk using main CVD risk factors alone.¹

Data are limited due to the fact that family history is poorly recalled by individuals as it requires knowledge of both age of diagnosis as well as nature of the CVD. This information is often poorly documented in primary care records.⁴¹

First Nations people

First Nations communities experience morbidity and mortality resulting from CVD when they are on average 10–20 years younger than their non-Indigenous peers.³⁷

The same age thresholds for family history of premature CVD in non-Indigenous Australians are applied for First Nations people, noting the premature onset of disease across the population.

Chronic kidney disease

1. For people with diabetes, eGFR and uACR are included in the CVD risk algorithm on which the Aus CVD Risk Calculator is based.¹,²

General considerations

Traditional risk equations may underestimate risk in people with chronic kidney disease (CKD).⁴²

People with CKD are at increased risk of CVD compared with the general population, and those with moderate-to-severe CKD are at high CVD risk.¹⁹,⁴³-⁴⁵

In people with CKD, assessing both uACR and eGFR levels provides greater accuracy in predicting 5-year CVD risk.⁴⁴

When general population and high-risk cohorts are analysed together, the risks of CHD, stroke and cardiovascular death increase steadily with decreasing eGFR and increasing uACR (see Table 7). ⁴⁴

At a population level, CVD risk is lowest at eGFR 95mL/min/1.73m² but increases at eGFR levels below this value. ⁴⁴ The risk of experiencing a CVD event (CHD, stroke, heart failure or death) increases steadily as eGFR decreases to levels below 75mL/min/1.73m².⁴³

However, in people with CKD, but without CVD, eGFR level >105mL/min/1.73m² is associated with an increased 5-year risk of experiencing a CVD event.⁴⁰

Table 7: Approach to CVD risk stratification according to kidney function (for people without diabetes)

Practice points

• Consider measuring eGFR and uACR when assessing CVD risk, as these tests independently improve prediction of cardiovascular events beyond traditional CVD risk factors alone.
• eGFR is commonly measured when assessing other CVD risk factors and is automatically reported by Australian pathology laboratories with requests for serum creatinine in people aged ≥18 years.

First Nations people

CKD is a significant health concern for First Nations people, who experience the condition at more than double the rate of the non-Indigenous population.⁴⁶

Studies suggest that adjusting estimated CVD risk based on glomerular filtration and/or persistent uACR measurements is appropriate in these populations.⁴⁷-⁴⁹

Support for the recommendations

A meta-analysis of cohort studies in people without CVD found that assessing eGFR and uACR in addition to assessing traditional CVD risk factors (including smoking status, age, sex, blood pressure, cholesterol level) significantly improves the ability to discriminate between people who will or will not experience cardiovascular events (e.g. CHD, stroke, and cardiovascular mortality), including in people without diabetes or hypertension. ⁴⁴

Severe mental illness

1. Terminology of ‘severe’ and ‘serious’ mental illness varies between conditions and across research, clinical practice and public health policy contexts, and these classifications can overlap. Grouping these under a single term is problematic. The definition used in this guideline is derived from the supporting evidence from the PREDICT cohort.⁵⁰

General considerations

Severe mental illness in this guideline is defined as a current or recent mental health condition requiring specialist treatment, whether received or not, in the 5 years prior to the CVD risk assessment.

CVD is a leading cause of illness and premature death in people living with severe mental illness.⁵⁰,⁵³ Assessing CVD risk is therefore a high priority in all people living with a mental health condition. However, CVD risk equations may particularly underestimate risk in people living with a mental health condition.

Increased CVD risk in people living with a mental health condition may be due, in part, to factors such smoking, poor nutrition, alcohol use, overweight and obesity, sedentary behaviours and lack of physical activity as well as the adverse effects of some medicines used to treat mental health conditions.

The mean age of diagnosis of depressive disorders and bipolar disorder is late twenties, although the onset of symptoms typically occurs before age 20.⁵¹ Early CVD risk factor assessment is warranted in this group, as the person may already be at significant risk of CVD. Smoking rates are particularly high and advising and helping people to cease smoking is a high priority (see Manage CVD Risk).

Treatment with second-generation (‘atypical’) antipsychotic agents is associated with an approximately 29% increased CVD risk in women and 14% increased CVD risk in men.³⁹

The recommendation applies more broadly than the people who are presently receiving specialist treatment for a severe mental health condition, as it is recognised that there are many people who require but are not receiving specialist treatment associated with inequity, living remotely or other factors.

Practice points

• In all adults living with severe mental illness, routinely assess CVD risk and promptly and effectively manage CVD risk factors.
• Communicating CVD risk to an individual living with severe mental illness may cause undue anxiety; carefully explain the risk in a supportive way that, if possible, will educate and motivate them to manage any relevant risk factors.
• When prescribing antipsychotic therapy, routinely monitor and address lifestyle^* and metabolic factors, and support the person to adopt and maintain healthy habits. The first 12 months of treatment are critical for avoiding rapid weight gain and metabolic changes. Assess weight at baseline and reassess at 1 month then every 3 months thereafter.
• Current Australian national guidelines for managing psychiatric disorders emphasise managing CVD risk⁵¹,⁵³ and modifying lifestyle^* as foundational care for both the mental disorder⁵¹ and to minimise the risk of developing a chronic health condition.⁵⁴

First Nations people

First Nations people experience higher rates of mental health conditions and psychological distress, connected to dispossession, discrimination and disadvantage within the context of ongoing colonisation.

In 2018–19, 24% of First Nations people aged 2 years and older reported having a mental or behavioural condition.⁵⁵ Furthermore, 31% of First Nations people aged 18 years and over experience high or very high levels of psychological distress, compared to 13% of their non-Indigenous peers.⁵⁵

Cross-sectional studies in First Nations communities have identified an association between depression and CVD.⁵⁶,⁵⁷ This is likely a bi-directional relationship.

Considering mental health when assessing and managing CVD risk is therefore important given the greater prevalence of mental health conditions and burden of CVD experienced by this population.

Social and emotional wellbeing is a concept that encompasses connection to culture, spirit, community, family and country, and incorporates biomedical perspectives of mental health.⁵⁸

Positioning mental health within the understanding of social and emotional wellbeing held by First Nations people can place a positive emphasis on the subject, facilitate wellness and be a key component of discussing and managing CVD risk and lifestyle^* factors.

Practice points

• Instruments developed specifically to measure social and emotional wellbeing in First Nations people should be used in preference to tools developed exclusively in non-Indigenous populations. These tools reflect First Nations people’s understandings and concepts of social and emotional wellbeing and mental health issues.⁵⁹,⁶⁰
• Refer to the mental health section of the National guide to a preventive health assessment for Aboriginal and Torres Strait Islander people³⁵ for recommended tools.

Resources

1. Heart risks resources for Aboriginal and Torres Strait Islander Peoples - National Heart Foundation of Australia
2. National guide to a preventive health assessment for Aboriginal and Torres Strait Islander people (mental health section) - RACGP

Support for the recommendation

A large cohort study in adults without prior CVD found that severe mental illness was associated with a 37% increase in the risk of cardiovascular events at follow-up (maximum 12 years; mean 4.5 years).⁵⁰ This risk increase was higher for women (64% higher) than men (29% higher).⁵⁰ CVD risk was also increased in people living with a mental health condition that was not considered ‘severe’.

Coronary artery calcium score

General considerations

Coronary artery calcium (CAC) measurement is performed by computed tomography. Unlike coronary angiography, it does not require contrast or intravenous access. Coronary angiography is not considered in this guideline as it is used in people with suspected or known CHD.

The test provides a score related to the amount and density of calcified plaque for each coronary artery.⁶¹

Results are reported both as total CAC score in Agatston units (Au), representing an absolute measure of coronary calcium, and as a percentile based on the individual’s age, sex and ethnicity (representing a relative measure of coronary calcium).

The total CAC score can be useful – in addition to clinical risk assessment – to improve precision in individualised risk prediction of cardiovascular events and to inform pharmacological treatment decisions (Table 8). It has a strong negative predictive value. The percentile score is a measure of risk relative to an age- and sex-matched general population.⁶¹

Potential consequences of testing for CAC include:

• a low radiation exposure (similar to that of a mammogram)⁶¹
• the clinical and psychological effects of potentially receiving an unexpected adverse result
• the potential need for further investigations associated with incidental findings (e.g. lung nodules).⁶²

Using CAC score to assess CVD risk

CAC measurement is not recommended as a population screening test. The low yield of CAC scoring in low risk populations makes mass screening impractical.

It has limited utility for people in whom high CVD risk is identified and in whom evidence-based medical management is therefore indicated, since it is unlikely to change management decisions.

CAC measurement could be considered in the setting of CVD risk factors not already accounted for in the Aus CVD Risk Calculator as the risk score may be an underestimate. It may also be useful in addressing reluctance to initiate or adhere to medicines, as it assists the person in understanding their coronary atherosclerosis burden.

While the CAC score indicates the burden of calcium deposits in the coronary vessel, it cannot detect the degree of stenosis. Therefore, it should not be used as a standalone test for symptomatic patients (e.g. presenting with possible cardiac angina).⁶³

A high CAC score (>99 Au), with visualisation and information about what this means, may enhance shared decision-making and promote adherence to preventive treatment (pharmacological and lifestyle* modification strategies) and may help with treatment hesitancy.⁶⁴,⁶⁵

In patients with a normal CAC score (zero), it is reasonable to repeat the test within 2–5 years to detect an increase in score and reclassify risk, based on available evidence. A prospective cohort study found that, among patients with a zero CAC score, 25% developed CAC over a period of 5 years.⁶⁶

Table 8: Clinical applications of CAC testing

Special considerations

Younger adults

The added diagnostic value of a CAC score of 0 is highly dependent on age.

A CAC score of 0 indicates a very low risk of cardiovascular events and mortality within 5 years⁶⁷,⁶⁸ but does not rule out non-calcified atherosclerosis, particularly in younger people.⁶⁹

Older adults

CAC increases with age and may have less discriminative value in people older than 75 years as most have high scores.⁶⁹

Practice points

• If CAC measurement is performed, the result could influence assessment of CVD risk in the following situations (Table 8):
  • In people considered to be at intermediate risk, a CAC score of 0 could reclassify them to a lower CVD risk category
  • In people considered at low or intermediate risk, a CAC score >99 Au (or ≥75^th percentile for age and sex), could reclassify a person’s CVD risk category to a higher level.
• In either case, carefully explain the estimated risk and manage risk according to current recommendations in discussion with the person and with appropriate follow-up and monitoring (see Manage CVD risk).
• If a CAC score has been obtained previously, the test should only be repeated if CVD risk category or management decisions are uncertain.
• If the initial CAC score was 0, consider reassessing CVD risk in 2–5 years, depending on baseline risk profile (see Assessment frequency and intervals).
• Do not repeat a CAC test if management would not change as a result of the score (e.g. for people already taking long-term BP-lowering and/or lipid-modifying pharmacotherapy).
• When considering obtaining a CAC score or discussing the results, explain to the person why the test is being done and how the results would guide treatment choices. Involve the person in all management decisions and pre-test counselling prior to performing a CAC test.
• Reporting CAC findings may differ according to the software used. Percentiles may be based on different populations. Clarify the report with the imaging provider, if needed.
• CAC testing is not presently subsidised by Medicare. Cost can vary considerably between providers.
• CAC testing is commonly used, and it is possible for people to present having already had the test, often for indications outside the present guideline. The practitioner should consider this result in the context of the Aus CVD Risk Calculator as a potential reclassification factor (e.g. a CAC score of 0 suggests that the calculator could overestimate risk, especially in older people, and a CAC >100 Au could imply underestimation of risk by the calculator).

Support for the recommendations

A systematic review comparing the predictive value of CAC score combined with a traditional CVD risk prediction model (Pooled Cohort Equations or Framingham Risk Score), with a traditional risk prediction model alone, concluded that there were too few well-designed clinical trials to determine its value in guiding management in adults without known CVD.⁶²

Other risk considerations

This section provides guidance on several clinical conditions, investigations and blood biomarkers that are associated with increased CVD risk.

Some of these risk markers provide very little discrimination value beyond that of traditional CVD risk factors and are not recommended as part of routine CVD risk assessment.

Others may be considered by clinicians for relevant groups, depending on clinical context.

Recommendations are provided where existing systematic reviews were available or where systematic reviews were conducted for this guideline.

Several other factors that are considered in the literature but may not reclassify risk beyond traditional CVD risk prediction equations, are discussed below.

Ankle-brachial index

General considerations

Ankle-brachial index (ABI) is a predictor of CVD risk in people with no previous history of coronary heart disease⁷⁰ but it provides little additional discrimination value when added to traditional risk calculators.⁶²

Practice points

• Although ABI is not recommended for CVD risk assessment, or in routine testing in people who are asymptomatic, it is useful in assessing people with suspected, or at high risk for, peripheral vascular disease.
• ABI should only be performed by suitably trained practitioners. Specific training is required as it is difficult to ensure consistently correct technique; it can be time-consuming and necessitate rest periods, and the test may cause the person discomfort or lead to anxiety or concern when a pulse is not readily found.⁷¹,⁷²

Support for the recommendation

A systematic review of cohort studies found that adding ABI to CVD risk prediction models results in no or negligible improvement in the model’s ability to identify who will or will not have a cardiovascular event.⁶²

High-sensitivity C-reactive protein

General considerations

C-reactive protein (CRP) is a nonspecific marker of inflammation used to monitor bacterial infection, inflammation, neurodegeneration, tissue injury, and recovery.⁷³ CRP levels are also raised in various chronic inflammatory diseases including CVD (atherosclerosis, chronic heart failure).⁷³,⁷⁴

Evidence supports using the high-sensitivity CRP test (hs-CRP) as a measure of chronic inflammation.⁷⁴ It has also been used as a marker of CVD risk in people without known CVD.⁷⁴

However, there is inconsistent evidence that hs-CRP improves rates of appropriate reclassification into clinically meaningful CVD risk strata.⁶² Its use is therefore likely to result in more people being incorrectly reclassified to a higher risk category.⁶²

While routine hs-CRP testing is unlikely to improve CVD risk assessment in the general population, persistently elevated CRP in people with chronic inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis or psoriasis), but no known CVD, may be a useful predictor of an increased risk of cardiovascular events.⁷⁵,⁷⁶

Support for the recommendation

A systematic review of cohort studies compared cardiovascular risk prediction models using traditional CVD risk factors alone with hs-CRP in addition to traditional risk prediction models (e.g. Framingham Risk Score or Pooled Cohort Equations) in asymptomatic adults with no known CVD. The review reported inconsistent findings, with no (or a very small) improvement in predicting cardiovascular events.⁶²

Chronic inflammatory conditions – rheumatoid arthritis

General considerations

People with rheumatoid arthritis or other chronic inflammatory conditions characterised by elevated C-reactive protein (CRP) levels are at increased risk of CVD compared with the general population.⁷⁷-⁷⁹

However, the accuracy of CVD risk prediction is not improved by incorporating the presence of rheumatoid arthritis or by adjusting estimates made by traditional CVD risk calculators. This practice may overestimate CVD risk.

Practice points

• People with rheumatoid arthritis or certain other chronic autoimmune inflammatory conditions are at increased risk of CVD⁷⁹ and should be followed up regularly (e.g. annually) for heart health checks and routine CVD risk assessment (noting that the accuracy of CVD risk prediction is not improved by incorporating the presence of rheumatoid arthritis into the calculation).
• A recent cohort study showed that systemic sclerosis, Addison’s disease, systemic lupus erythematosus and type 1 diabetes were associated with the highest overall cardiovascular risk.⁷⁹

Support for the recommendation

Pooled data from seven cohort studies in European, American and African populations indicated that, in people with rheumatoid arthritis (but without known CVD), three algorithms that incorporated the presence of rheumatoid arthritis did not predict CVD risk more accurately than risk calculators developed for the general population (mean follow-up approximately 7 years).⁸⁰

History of pregnancy complications

Hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy are associated with an increased risk of CVD. A history of hypertensive disorders during a first pregnancy triples a woman’s risk of developing CVD in the following 10 years.⁸¹,⁸² A thorough pregnancy history should therefore be taken when performing a CVD risk assessment.

Hypertension may begin before or during pregnancy.⁸³ Hypertension during pregnancy is defined as >140mmHg systolic or >90mmHg diastolic BP measured over repeated readings.⁸⁴,⁸⁵

Hypertension diagnosed after 20 weeks’ pregnancy is either gestational hypertension (in the absence of proteinuria and without biochemical or haematological abnormalities) or pre-eclampsia.⁸³,⁸⁶

Women with early-onset (<34 weeks) versus late-onset hypertensive disorders of pregnancy have a greater risk of CVD.⁸¹

Pre-eclampsia

Pre‐eclampsia is a multisystem disorder affecting approximately 2–5% of pregnant women and is a major cause of maternal and perinatal morbidity and mortality.⁸⁶,⁸⁷

It is defined as new-onset hypertension after 20 weeks’ gestation, with evidence of proteinuria and/or acute kidney injury, liver dysfunction, neurological involvement, thrombocytopaenia, haemolysis or foetal growth restriction.⁸⁷

It is unclear whether pre-eclampsia initiates the damage to the mother’s cardiovascular system, leading to CVD later in life, or whether pre-eclampsia, and later CVD, share common risk factors preceding the pregnancy.⁸⁸

Women with a history of pre-eclampsia have approximately 1.5–2.7 times higher long-term risk of CVD than women in the general population.⁸⁸,⁸⁹ Evidence shows a higher risk of developing hypertension and CVD in women with recurrent pre-eclampsia compared with women with a single episode of pre-eclampsia.⁹⁰ CVD risk is also higher in women who experience pre-eclampsia and another pregnancy complication such as gestational diabetes.

The increased risk of cardiovascular events persists beyond 10 years after pregnancy.⁸²,⁸⁹,⁹¹,⁹²

Pre-eclampsia is also associated with more than three times increased risk of developing later hypertension and kidney disease, and double the risk of developing type 2 diabetes, compared with women who were normotensive during pregnancy.⁸⁹

Gestational diabetes

It is estimated that women with a previous diagnosis of gestational diabetes have a two-fold increased risk of developing coronary artery calcification – associated with increased CVD risk – even if they maintain healthy blood glucose levels postpartum.⁹³

Despite the increased risk of developing type 2 diabetes following a pregnancy complicated by gestational diabetes, many women with gestational diabetes do not have recommended regular postpartum blood glucose checks.⁹⁴

Practice points

• Take a thorough pregnancy history when performing a CVD risk assessment.
• For women with a history of hypertensive disorders and/or pre-eclampsia, particularly early-onset pre-eclampsia (<34 weeks), consider an annual blood pressure check and regular assessment of other heart disease risk factors.
• Women with a history of gestational diabetes who are planning another pregnancy should have an oral glucose tolerance test annually. However, if results are normal (i.e. no diabetes or impaired glucose tolerance), then this can be changed to a fasting blood glucose and HbA1c test at least every 3 years.⁹⁵,⁹⁶ Explain this elevated risk and the need for monitoring, and the importance of leading a healthy lifestyle^*.

First Nations people

Quasi-national data from 2016–2018, suggested that about 6% of First Nations women giving birth experienced pregnancy-induced hypertension, compared with about 5% of non-Indigenous women.⁹⁷

The limited available evidence suggests that First Nations women experience higher rates of hypertensive disorders and pre-eclampsia during pregnancy, compared with non-Indigenous women.⁹⁸,⁹⁹

First Nations women also experience higher rates of gestational diabetes compared with non-Indigenous women.¹⁰⁰,¹⁰¹

Support for the advice

Evidence from a meta-analysis found that early-onset pre-eclampsia (defined as requiring delivery before 34 weeks’ gestation) was associated with a more than five-fold higher risk of CVD and cerebrovascular conditions compared with late-onset pre-eclampsia.⁸⁹

Premature or early menopause

General considerations

Menopause before 45 years of age is associated with increased risk of CVD, but current evidence does not demonstrate how this factor should be incorporated into CVD risk stratification for women.

The association between premature menopause and increased CVD risk is also seen in women who have undergone hysterectomy, with or without oophorectomy.¹⁰²,¹⁰³

However, it is unclear whether CVD risk associated with age of menopause is independent of other factors such as blood pressure or lipid profiles.

Current evidence suggests that women who experience premature or early menopause may need earlier and closer monitoring of CVD risk in clinical practice.

Practice points

• For women with a history of premature menopause, consider an annual blood pressure check and regularly assess other heart disease risk factors.
• A discussion about menopause provides an opportunity to explain the elevated risk of CVD associated with early menopause, the need for increased monitoring, and the importance of leading a healthy lifestyle. Refer to an appropriate allied health professional, if required (see Manage CVD risk - addressing lifestyle risk factors)

Support for the advice

A meta-analysis of observational studies from Australia, Scandinavia, the USA, Japan, and the UK, found that naturally occurring premature (<40 years) and early (40–44 years) menopause are associated with clinically important (1.3–1.5 times) increases in the risk of CHD or stroke events before the age of 60 years, compared with women who experience menopause at age 50–51 years.¹⁰⁴

These findings are supported by other meta-analyses¹⁰⁵,¹⁰⁶ and observational studies.¹⁰²,¹⁰⁷

Lipids

Ongoing research is assessing whether a more accurate prediction of CVD can be achieved by measuring plasma concentrations of other lipid fractions, such as:

• non-high-density lipoprotein (non-HDL) cholesterol
• lipoprotein(a) (Lp(a)), comprised of LDL and apolipoprotein (a)
• apolipoprotein B-100 (apoB).

Routinely measuring these fractions in people without known CVD is not currently recommended for inclusion in risk-estimating algorithms.⁸⁸,¹⁰⁹,¹¹⁰

Elevated plasma triglyceride concentrations predict increased CVD risk in people without CVD, ¹¹¹ but not independently of HDL cholesterol and apoB concentrations.¹¹¹,¹¹²

Using non-HDL cholesterol, apoB and apolipoprotein A-I may not be substantially more accurate than using ‘traditional’ lipid concentrations (i.e. total cholesterol and HDL cholesterol) in discriminating between people who will develop CVD and those who will not.¹¹³ However, non-HDL cholesterol and apoB levels are better predictors of cardiovascular events than LDL cholesterol.¹¹⁴,¹¹⁵

High plasma levels of Lp(a) strongly predict atherosclerotic CVD in people with familial hypercholesterolaemia (FH) confirmed by genetic testing.¹¹⁶,¹¹⁷

Although Mendelian studies show increased CVD risk associated with elevated Lp(a) levels, no randomised controlled trials have investigated the effect of reduced plasma Lp(a) on CVD events.¹¹⁸

There is currently no justification for Lp(a) screening in the general population, but it may be considered in a secondary prevention setting, for individuals with FH, in adults with recurrent or premature CVD events, or if LDL-C lowering is suboptimal or the individual experiences recurrent CVD events despite being on therapy.¹¹⁹

Polygenic risk scores

General considerations

A polygenic risk score is a single value that measures the cumulative genetic risk of a person conferred by their genetic variants.¹²⁰

Polygenic risk scores can be applied at any age and have been developed as a strategy for predicting CVD risk years before CVD develops, without relying on traditional risk prediction algorithms.

A substantial proportion of people who develop MI do not have known modifiable CVD risk factors before their diagnosis and so cannot be identified for preventive strategies.¹²²-¹²³

Large retrospective cohort studies have demonstrated strong associations between genetic risk scores and CHD events, which are independent of family history of premature CVD and provide a more accurate prediction of cardiovascular events than traditional CVD risk factors.¹²⁴-¹²⁹

However, risk estimates based on traditional risk algorithms correlate poorly with those from polygenic risk scores¹³⁰ suggesting that these approaches might be complementary.

Practice points

• The large number of polygenic risk scores being developed will require consensus and harmonisation before they can be widely used.¹³¹
• Effective implementation of polygenic risk scores in practice will require training in interpretation for clinicians, communication of risk to people undergoing the test, and strategies and protocols for ensuring data security.¹³¹
• People with no conventional CVD risk factors may be unwilling to commit to long-term preventive therapies based on a polygenic risk score alone.

COVID-19

Research carried out since the start of the COVID-19 pandemic has established that COVID-19 infection worsens pre-existing cardiovascular conditions and that people living with pre-existing CVD are more likely to die due to COVID-19 infection.¹³²,¹³³

CVD events (including MI, pericarditis, myocarditis, heart failure, arrythmias and stroke) are increased in people who survive COVID-19 infection, regardless of the severity of their infection, their age, race, sex or other risk factors for CVD.¹³³ The severity of COVID-19 infection can be directly correlated with an increased risk of developing cardiovascular complications including heart failure and stroke.¹³³

The risk of CVD and complications (including MI, pericarditis, myocarditis, heart failure, arrythmias and thromboembolic events) is highest during the first 30 days after COVID-19 infection. However, this risk remains elevated for up to 12 months and possibly longer.¹³²,¹³³ The risk of developing CVD and CVD complications is increased even in people considered at low risk of CVD before COVID-19 infection, and therefore previous COVID-19 infection should be considered when assessing CVD risk.¹³³

There is still uncertainly about the best way to support, treat and manage people living with long COVID or post-COVID conditions.

Practice points

• Establish whether the person has had a COVID-19 infection in the past.
• Assess CVD risk factors in people who have had a COVID-19 infection or are living with long COVID.
• Refer people with suspected COVID-19-induced myocarditis, pericarditis, cardiomyopathy or heart failure for specialist care.
• Ensure that priority groups including First Nations people, people from cultural and linguistically diverse populations, and people living in remote communities who have had COVID-19 infections or are living with long COVID, have access to and receive, culturally appropriate long-COVID rehabilitation and ongoing cardiac care.

*  This guideline refers to certain modifiable risk factors as ‘lifestyle’ factors. However, it is recognised that these behaviours are not necessarily an individual’s choice, but reflect the complex interplay of social, cultural, and environmental factors, which may be further influenced by clinical conditions. Use of the term ‘lifestyle’ does not attribute blame to a person.