Cardiovascular Health, Risk Markers and Early Diagnosis

The Risks That Silently Threaten Your Heart: Cardiovascular Health and Early Diagnosis

Cardiovascular diseases have long been among the leading causes of death in Cyprus, as they are worldwide. Every year, millions of people die from heart attacks, strokes, or sudden vascular occlusions, largely due to preventable causes (Mensah et al., 2019; WHO, 2021). This clearly demonstrates that these diseases are not only an individual but also a societal health problem.

However, awareness of such a widespread and devastating threat remains insufficient. Many individuals only learn they are at risk when they experience a clinical crisis. This "silence" highlights a fundamental public health problem: cardiovascular risks are not identified in a timely manner, and preventive interventions are not implemented early enough (Libby, Ridker, & Hansson, 2009).

While conventional approaches often equate cardiovascular disease with "high cholesterol," modern science reveals a much more complex network of interactions affecting heart health. The roles of biological processes such as inflammation (hidden inflammatory processes), oxidative stress, endothelial dysfunction (disorders in the lining of blood vessels), and metabolic syndrome (e.g., sugar and blood pressure imbalances) are now clearly defined (Hansson, 2005; Ridker, 2003). Current advanced biomarkers, such as high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a), apolipoprotein B, and homocysteine levels, allow for early risk assessments that are not detectable by conventional tests.

Timely implementation of these tests not only prolongs life but also significantly improves quality of life by preventing processes that could lead to heart attack or stroke (Mendis et al., 2011). Preventive medicine, in this sense, forms the basis of the modern approach to healthcare: identifying and preventing diseases before they occur, rather than treating them.

Why Are Cardiovascular Diseases So Common in Cyprus?

Cyprus is a region where genetic predisposition and environmental risk factors significantly overlap. Traditional dietary habits, particularly excessive salt and saturated fat consumption, low physical activity levels, increased obesity prevalence, and widespread smoking in men, are among the main risk factors for cardiovascular disease (Yusuf et al., 2004; WHO, 2022). These lifestyle factors also increase the prevalence of metabolic syndrome in the population and lead to the onset of silent disorders such as hypertension, dyslipidemia, and insulin resistance at earlier ages (Ng et al., 2014; Mensah et al., 2019).

Kuzey Kıbrıs’a özgü mortalite verileri, bu risk faktörlerinin kardiyovasküler sonuçlara dönüştüğünü açıkça göstermektedir. 2007–2016 dönemine ait epidemiyolojik analizler, iskemik kalp hastalıklarının bölgedeki en yaygın ölüm nedeni olduğunu ortaya koymuştur. 2007 yılında tüm ölümlerin %31.78’i iskemik kalp hastalığına bağlı olarak gerçekleşmiş; bu oran ilerleyen yıllarda daha da artmıştır (Yücel et al., 2020). Erkeklerde bu hastalığa bağlı ölüm oranı, kadınlara göre yaklaşık 1.9 kat daha yüksektir (Yücel et al., 2020).

Kıbrıs Cumhuriyeti genelindeki (Güney Kıbrıs) veriler de benzer şekilde kalp-damar hastalıklarının baskın morbidite ve mortalite nedenleri olduğunu doğrulamaktadır. 2021 yılı verilerine göre, kardiyovasküler hastalıklar tüm ölümlerin yaklaşık %34.6’sını oluşturmaktadır; yaşa göre ayarlanmış mortalite oranı ise 100.000 kişi başına yaklaşık 185’tir (World Heart Federation, 2024). Bu ölümlerin önemli bir kısmını iskemik kalp hastalıkları ve inme oluşturmaktadır (OECD, 2023). Bu oranlar, Kıbrıs’ın Avrupa ortalamalarının üzerinde bir kardiyovasküler hastalık yükü taşıdığını göstermektedir.

Given these data, the need for preventive health strategies in Cyprus is clear. Early screening, monitoring of inflammatory biomarkers such as hs-CRP, regular monitoring of metabolic parameters, and the widespread adoption of lifestyle interventions throughout the population are critical to reducing regional cardiovascular mortality (Mendis et al., 2011). Preventive medicine not only protects individual health but also reduces the economic burden on healthcare systems.

Just Looking at Total Cholesterol Is No Longer Enough

In traditional cardiology practice, LDL (low-density lipoprotein) has generally been defined as "bad cholesterol" and HDL (high-density lipoprotein) as "good cholesterol." While this classification was popularized to facilitate a public understanding of cholesterol metabolism, in recent years, many scientists have argued that this approach is both biologically unfounded and clinically misleading.

First and foremost, it must be taken into account that LDL and HDL are not cholesterol molecules themselves, but merely lipoprotein structures that transport cholesterol and other lipids. Therefore, labeling these structures as "good" or "bad" does not align with biological reality (Attia, 2023). It is emphasized that such terms are not scientific, but rather public relations, and that they simplify complex pathophysiological processes, leading to misunderstandings.

Furthermore, the effect of LDL on atherosclerotic risk depends not only on the amount of cholesterol it carries but also on the number of particles (LDL-P), their size, and their density. Small, dense LDL particles, in particular, have been shown to more easily pass through the vascular endothelium, leading to a higher potential for oxidation and plaque formation (Sniderman et al., 2019). This suggests that risk stratification based solely on LDL cholesterol levels may be inadequate.

HDL has long been considered the "good cholesterol," and increased plasma levels are generally considered a protective factor. This is based on the role HDL plays in reverse cholesterol transport and its anti-inflammatory and anti-oxidative properties (Rosenson et al., 2016). However, this traditional approach has been questioned in recent years, with the functional capacity of HDL, rather than its quantity, being shown to be more closely related to clinical outcomes. In particular, the variable capacity of HDL particles to suppress inflammation and transport cholesterol back from the arterial wall suggests that high HDL levels alone cannot be considered safe (Rohatgi et al., 2014).

Furthermore, it has been shown that very high HDL levels (e.g., >100 mg/dL), observed in some individuals, may paradoxically be associated with cardiovascular risk. This may generally be due to structural or functional abnormalities of HDL, oxidative modifications, or alterations in the biological effects of the proteins it carries (e.g., paraoxonase-1, apolipoprotein AI) (Ko et al., 2016). Some genetic mutations (e.g., individuals carrying CETP inhibitors) may increase HDL levels while impairing its anti-atherogenic functions, leading to clinically neutral or adverse effects. Furthermore, in some inflammatory and autoimmune diseases, despite high HDL levels, HDL may exhibit functionally “dysfunctional” HDL (Besler, Luscher, & Landmesser, 2012).

These findings suggest that clinical interpretation of HDL should consider not only quantitative data but also context and the individual's metabolic status. Therefore, a "higher is better" HDL assessment is no longer appropriate for modern lipidology and cardiovascular risk analysis.

In light of all these findings, it appears that the concepts of "good" and "bad" cholesterol are insufficiently descriptive in clinical decision-making. It is now widely accepted that factors such as particle-based lipid analyses, inflammatory markers, insulin resistance indicators, and genetic predisposition should also be considered in the assessment of cardiovascular risk. In this context, current scientific understanding recommends assessing individuals based not only on LDL and HDL levels but also on a more comprehensive metabolic risk profile (Attia & Agatston, 2023).

New Generation Risk Markers:

ApoB (Apolipoprotein B)

One of the most accurate tests that measures the actual number of "atherogenic" or vessel-clogging particles in the blood. Apolipoprotein B (ApoB) While LDL cholesterol levels have traditionally been used as a basis for determining cardiovascular disease risk, it is now known that the number of lipoprotein particles carrying this cholesterol, or ApoB concentration, is more of a predictor of atherosclerosis development than the amount of LDL itself. Because each atherogenic particle (LDL, IDL, VLDL, and Lp(a)) contains a single ApoB molecule, the ApoB level in the blood is a direct indicator of the total number of atherogenic particles (Sniderman et al., 2019).

In individuals with high ApoB levels, these particles come into greater contact with the vascular wall, causing endothelial dysfunction, inflammation, and ultimately, atherosclerotic plaque development. This process often proceeds asymptomatically, with clinical findings only appearing in advanced stages. Therefore, high ApoB levels are considered a sign of a "silent but dangerous" atherosclerosis process (Ference et al., 2017).

The European Atherosclerosis Society (EAS) and European Society of Cardiology (ESC) guidelines published in 2023 recommend ApoB testing for the stratification of cardiovascular risk. primary biomarker According to guidelines, ApoB measurement provides more accurate risk assessment than traditional lipid profiling, especially in individuals with metabolic syndrome, diabetes, or high triglyceride levels (Mach et al., 2023).

Lp(a) – Lipoprotein (a)

Lipoprotein(a), also known as Lp(a), is a genetically determined, independent, and potent cardiovascular risk factor that cannot be detected by conventional cholesterol tests. This lipoprotein, structurally similar to the LDL particle, contains an additional protein called apolipoprotein(a). This structure poses a dual threat that can cause both atherosclerosis and thrombosis (Tsimikas, 2017). Lp(a) particles disrupt endothelial function, leading to inflammation and plaque formation, while also increasing clotting tendency by suppressing fibrinolysis (Berglund et al., 2022).

Lp(a) levels are largely genetic and cannot be significantly reduced by lifestyle changes. Genetic Lp(a) elevations are reported to be more common in Mediterranean communities, particularly those of Cyprus. This suggests that geographic and ethnic origins may be a determining factor in Lp(a) levels (Nordestgaard et al., 2010).

Individuals with elevated Lp(a) levels have a significantly increased cardiovascular risk, even if total cholesterol or LDL levels are within normal limits. Therefore, individuals with elevated Lp(a) levels should be considered high-risk, even if their classical lipid profile is normal (Wilson et al., 2024). Current guidelines recommend measuring Lp(a) levels, particularly in individuals with a history of premature heart disease or unexplained cardiovascular events (ESC/EAS, 2023).

hs-CRP (High-sensitivity C-Reactive Protein):

High-sensitivity C-reactive protein (hs-CRP) is a reliable biomarker of chronic, low-grade inflammation. Current research suggests that atherosclerosis (the plaques that cause heart attacks) develops not only from cholesterol accumulation but also from an ongoing inflammatory process in the arterial wall (Hansson, 2005). We now know that cardiovascular events such as myocardial infarction (heart attack) are not simply the result of a blockage in the artery but are also associated with inflammation-induced atherosclerotic plaque rupture and thrombosis (Libby, Ridker, & Hansson, 2009).

hs-CRP levels above 2 mg/L indicate increased intravascular inflammation and a greater likelihood of atherosclerotic plaque instability in these individuals (Ridker, 2003). This leads to a significantly increased risk of heart attack and ischemic stroke.

For example, the JUPITER study found that individuals with hs-CRP levels ≥2 mg/L had a significantly increased risk of cardiovascular events, even when LDL cholesterol levels were normal (Ridker et al., 2008). Therefore, hs-CRP is considered an important complementary parameter for assessing intravascular inflammatory burden, in addition to classical risk factors.

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Although new generation tests have the capacity to better guide us about our cardiovascular health, it is still very important to perform classical tests and evaluate all markers together.

It's recommended that everyone, especially men over 35 and women over 40, regardless of their risk group, have these tests at least once a year. Screening becomes even more critical for those with a family history of early heart attacks, smokers, or those with diabetes or hypertension. These tests not only provide numerical data but also allow you to develop the most appropriate lifestyle changes and, if necessary, treatment plans.

“Risk is most dangerous when it goes unnoticed."

The most effective way to prevent the increasing prevalence of heart disease in Cyprus is to identify risk factors early and take action. Modern laboratory tests should no longer be used just when "something goes wrong," but when everything is going well. Because being healthy is more than just not being sick.

As the first person to bring these tests to Cyprus, I hope to contribute to your cardiovascular health.

I wish you healthy days,

Dr. Ahmet Özyiğit

Fellow in Anti-Aging and Metabolic Medicine
Elite Hospital