Understanding Cardiovascular Risk Factors: The Framingham Risk Score Calculator

In the last 65+ years, numerous studies and meta-analyses were done and a plethora of pharmacological treatments were developed. A few dozen diets appeared in the last 100 years and the lifestyle of the modern man changed radically multiple times. When adding all this clinical experience with all the fundamental research that was done in the last decade, researchers were able to pretty accurately pinpoint the most prevalent risk factors for cardiovascular disease and ASCVD as well as to develop treatment strategies for mitigating CVD events, such as MI, HF or stroke. ^{[8], [9], [10]}

Even as cardiovascular diseases still kill the most people worlwide compared to other diseases, morbidity was greatly reduced in the last decades, and life expectancy had slowly risen since the last century.

Some of the most important predictors of cardiovascular diseases and events, based on the studies that served for the creation of the most used CVD risk scores, are: ^{[6], [10], [12]}

1. Age: particulary if > 65 years old or >75 years old
2. Hypertension particularly, systolic blood pressure
3. Prior Stroke or MI ^[9]
4. Diabetes mellitus, active smoking
5. Male gender ^[8]
6. Total cholesterol, LDL and HDL levels ^[11]
7. African American or Hispanic descent ^[8]

Some of the most known and widely used risk prevention strategies are based on the following elements:

• Blood pressure lowering medications (usage of the 'polypill' is recommended, when appropriate, for optimisation of adherence)
• Lipid lowering medications ^[11]
• Dietary interventions particulary the Mediterranean diet, increasing fibre intake, nut consumption, reduced salt intake in patients with renal disease or carbohydrates in patients with diabetes mellitus and aggressive glycemic control
• Smoking cessation and alcohol consumption reduction to less than 14 units (one unit = 10gr. alcohol) per week irrespective of gender (NHS Alcohol guidelines)
• Physical exercise: 150 minutes of moderate-intensity physical activity and 2 days of moderate-high intensity -when appropriate - exercise per week
• Policy and legislative changes: food labeling, junk food taxation and subsidies, air pollution addressing, food and drink quality standards, health promotion-mass media campaigns a.o. ^{[10], [13]}

In conclusion, through decades of research and clinical experience, significant progress has been made in understanding and addressing cardiovascular health. By identifying prevalent risk factors and implementing effective prevention strategies, such as medication use, dietary interventions, lifestyle modifications, and policy changes, the burden of cardiovascular diseases and related events has been significantly reduced. However, it is crucial to continue promoting awareness and implementing evidence-based approaches to further improve heart health worldwide.

Cardiovascular disease (CVD) is the leading cause of mortality in both developed and developing countries worldwide. Throughout the 20th and 21st centuries, the incidence of CVD has rapidly increased, prompting extensive research to identify its causes and risk factors [1]. The rise in CVD can be attributed to several culprits: ^[2]

1. Rapidly Rising Risk Factors: CVD risk escalates due to various factors. Cellular genetic errors accumulate over time, making the heart and vascular system more vulnerable. Additionally, smoking, pollution, food additives, and preservatives damage blood vessels, leading to lasting effects on vital organs such as the brain and heart. These damages increase the risk of strokes and myocardial infarctions (MI). As global life expectancy rises, previously silent cases of CVD become more apparent, resulting in a worsened morbidity-mortality profile. ^{[1], [2]}
2. CVD at Younger Ages: The discussed risk factors can independently or collectively cause CVD, even among younger individuals, sometimes before the age of 50. ^{[1], [2]}

As cardiovascular diseases became more prevalent, researchers started gathering information on these risk factors for multiple reasons. Firstly, they aimed to identify the most prevalent risk factors and determine their impact on outcomes. Concurrently, various therapies and outcome-modification strategies emerged, prompting tests to assess their effectiveness in reducing mortality and improving the quality of life for patients [1].

Secondly, before the 1950s, medical specialists lacked tools to guide treatment plans, triage patients, and assess risks accurately. To address this gap, researchers began collecting data to develop risk prediction scores. These scores aimed to precisely calculate the risk of developing heart disease or dying from cardiovascular causes, enabling the identification of patients requiring the most attention and guiding treatment decisions, whether aggressive or conservative. ^{[1], [2]}

One of the pioneering studies in this field was The Framingham Heart Study, which examined nearly 5,200 patients aged 28 to 62 over a period of 14 years. This study aimed to identify the risk factors that had the most influence on heart health and determine whether a score could be developed to calculate the precise risk of developing heart disease or experiencing cardiovascular-related mortality. ^{[1], [2]}

• Success in Risk Score Development: The Framingham Heart Study succeeded in creating a risk score that remains one of the most widely used in cardiology. It was one of the first studies to uncover the primary causes of cardiovascular disease, sparking a revolution in the understanding of the heart's physiology and pathophysiology. ^{[1], [2]}
• Demonstrated Efficiency and Usefulness: The Framingham study was followed by two consecutive studies involving close to 14,000 patients. These studies not only confirmed the efficiency of the risk scores but also highlighted their usefulness in predicting cardiovascular risks. ^[1]

• Systolic Blood Pressure and Stroke: By the 1960s, stroke remained the third leading cause of death among Americans. The Framingham investigators, through clinical history, neurologic examination, and sometimes lumbar puncture, established the link between systolic blood pressure and stroke. Furthermore, they showed that hypertension conferred an even greater risk of stroke compared to coronary heart disease [2].
• Atrial Fibrillation and Stroke: The Framingham studies identified non-rheumatic atrial fibrillation as a potent risk factor for stroke. Chronic atrial fibrillation not due to rheumatic heart disease was associated with over a five-fold excess risk of stroke. These findings prompted the recommendation for controlled trials of anticoagulation or antiarrhythmic agents in individuals with chronic atrial fibrillation, leading to improved standards of care. ^{[1], [2]}
• Obesity and Atrial Fibrillation: The Framingham data emphasized the significant contribution of obesity to atrial fibrillation risk, independent of other factors such as hypertension and diabetes. The studies highlighted the underappreciated association between obesity and atrial fibrillation and its impact on heart failure risk. ^{[3], [4]}
• Genetic Determinants of CVD: The Framingham Heart Study contributed to the global effort to study the genetic determinants of complex diseases. Through this research, hundreds of common genetic variants influencing the risk of cardiovascular diseases have been identified, furthering our understanding of the genetic basis of CVD. ^[5]

One limitation of the original Framingham study was the predominantly white European descent of the cohort. To address this limitation, an additional 410 minority participants were recruited through the Omni 2 cohort. In response to the need for more accurate and inclusive risk scores, various organizations, including the American Heart Association (AHA), European Society of Cardiology (ESC), National Health Service (NHS) in the UK, and private organizations, developed their own risk scores. These scores either utilized larger patient data pools or focused on specific population subgroups to improve risk prediction accuracy and address diversity. ^[6]

The Framingham risk score, derived from the landmark Framingham Heart Study, has significantly contributed to our understanding of CVD risk factors and served as the foundation for subsequent risk assessment tools. However, the evolution of risk assessment continues with the development of alternative models, such as the scores developed by the AHA, ESC, NHS/NICE, and private organizations. These scores incorporate a broader range of risk factors and offer improved risk prediction, particularly in diverse populations. Enhanced risk assessment tools enable the identification of high-risk individuals and the implementation of effective preventive measures, ultimately promoting better cardiovascular health.

While multiple cohort studies and meta-analyses have confirmed the utility of major risk scores in triaging and managing patients with cardiovascular disease (CVD), atrial fibrillation (AF), and heart failure (HF), it is important to recognize the existence of discrepancies among these scores. It has been observed that these risk scores should not be solely relied upon but should be correlated with clinical data and other risk factors not considered by these scores, as suggested by recent studies. Furthermore, caution is advised when using these scores for patient populations not specifically recommended in the original studies. ^[10]

A study revealed that the ACC/AHA risk score tends to overestimate mortality rates across all risk categories. The authors demonstrated that both 5-year mortality and event rates were significantly lower than the predicted values, with the discrepancy being more prominent in lower risk categories (almost 3 times lower at risk scores <10% and almost 2 times lower at risk scores ≥10%). ^[16]

Another study found similar results but noted that the ACC/AHA risk score was not the most problematic. The ATP-III (Adult Treatment Panel III) score exhibited even greater discrepancies, while the RRS score (Reynolds Risk Score) provided the most accurate results, followed by the Framingham Risk Scores for CVD and CHD. ^[7]

When considering the initiation of statin treatment, the aforementioned discrepancies and tendency for overestimation become less relevant. However, caution should still be exercised when using the proposed 7.5% risk threshold for making decisions regarding prophylactic measures. Instead, healthcare providers should prioritize recommending lifestyle modifications such as dietary changes, exercise, and smoking cessation before considering pharmacological interventions, particularly when using the ACC/AHA or RRS scores.

The comparison between the Framingham risk score and the QRISK score reveals notable differences in their development and validation processes, leading to distinct performance outcomes. The QRISK risk scores demonstrate superior performance, which can be attributed to their development and validation on large cohorts of general practice patients in the United Kingdom, specifically targeted and designed for risk predictions in that population. These scores take into account crucial factors such as social deprivation, family history of coronary heart disease, and ethnicity, all known to significantly increase the risk of developing cardiovascular disease. ^[14]

In contrast, the Framingham score was developed on a relatively small and homogeneous sample of white individuals from a single town in the United States between 1968 and 1975. This narrower focus may limit its accuracy and applicability to diverse social and ethnic groups. Given the need for equitable risk prediction across all demographics in the United Kingdom, the QRISK scores, particularly QRISK2, emerge as a more accurate and preferable choice over the Framingham scores. ^[14]