Cardiovascular disease: a journey from risk factors through to end organ failure

Cardiovascular disease (CVD) is largely preventable, so it is perhaps surprising that it remains the most common cause of death worldwide.^1,2 An estimated 19.7 million people globally died from CVD in 2019.³ CVD is not a single disease but a spectrum of disorders affecting both the heart and blood vessels.^1,2 It incorporates diseases such as ischemia and coronary artery disease, cerebrovascular disease, and other vascular conditions such as hypertension, peripheral vascular disease, deep vein thrombosis and pulmonary embolism.^1,2

Underpinning all these is atherosclerosis, a complex process that deposits plaques of fatty material and cholesterol into the inner lumen of medium- to large-sized blood vessels.^1,2,4 Affected blood vessels become narrowed and less pliable, impairing blood flow, building pressure and eventually causing plaque rupture. This may lead to the formation of blood clots, potentially causing heart attack or stroke, the most common causes of death from CVD.^1-4

The journey begins: the importance of risk factors

Patients who experience a CV event such as a heart attack or stroke have travelled along a pathway of increasing morbidity and mortality that started with a risk factor known to promote the process of atherosclerosis.^1,5 There are multiple modifiable risk factors responsible for subclinical organ damage that increase the likelihood of a CVD diagnosis.^1,6 The first steps in this journey are usually behavioral: tobacco use, unhealthy diet, physical inactivity and harmful use of alcohol.^1,2

Unhealthy behaviors lead to the next step along the pathway where clinically observable metabolic and physiological changes occur causing raised blood pressure (hypertension), obesity, raised blood sugar (diabetes) and raised blood lipids (dyslipidemia).^1,2

Two of these risk factors represent the greatest contributors to CVD burden: dyslipidemia (high low-density lipoprotein cholesterol [LDL-C]) and hypertension.³ An accumulation of multiple risk factors can increase the risk of having a heart attack or stroke exponentially.^1,5 For example, compared to people with no risk factors, individuals who smoke and have dyslipidemia, hypertension and diabetes are 75% more likely to experience a heart attack.⁵

The hidden pathway of progression: dyslipidemia

Dyslipidemia is a term used to describe abnormally high levels of lipids in the blood, which over time cause atherosclerosis.^7,8 In particular, high levels of LDL-C are the key initiating event in atherogenesis and high levels of total cholesterol are indicative of increased cardiovascular risk.⁷ In recent years, another lipid abnormality, raised triglyceride levels, has been found to contribute as well.⁷

It is estimated that nearly 40% of the world’s population, approximately 3 billion people, have elevated total cholesterol.^9,10 However, less than 25% of these have been diagnosed and treated appropriately.¹¹

There are many societal guidelines and individual country guidelines for treating dyslipidemia and preventing CVD. Guidelines are based on landmark clinical trials, such as Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), Collaborative Atorvastatin Diabetes Study (CARDS), and Treating to New Targets (TNT), and are updated regularly as new clinical data and outcomes studies are completed.^7,12

The American College of Cardiology (ACC) and the American Heart Association (AHA) published a guideline with input from about a dozen other cardiology and lipid organizations.^12,13 This guideline divides patients into four main treatment groups. The first is a primary prevention group, where patients have multiple risk factors but have not yet had a CV event. The second group comprises diabetic patients. The third group are those with familial hypercholesterolemia, a condition characterized by extremely high LDL-C levels (≥190 mg/dL or ≥4.9 mmol/L). The fourth group are patients who have already had a CV event and the goal is to prevent a subsequent event. These secondary prevention patients are among the highest risk. No matter which group a patient falls into, these guidelines state treatment should be started early and aggressively in order to lower LDL-C levels and reduce CV risk.^12,13

The European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) guideline follows the same principle of treating earlier.⁷ It recommends beginning with lifestyle intervention to address modifiable risk factors, and then adding a statin as first-line treatment. Both American and European guidelines recommend titrating statins up to the highest tolerable dose before adding a non-statin therapy such as ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) to reduce LDL-C levels.^13,14 High-intensity statins will reduce LDL-C by more than 50% and are required for patients at the highest level of CV risk. There are currently two high-intensity statins: atorvastatin and rosuvastatin.

The pathway’s steep incline: hypertension

Across all modifiable risk factors, hypertension is the leading cause of CVD burden as reflected by an estimated 18.6 million cases worldwide in 2019.³ It is a major cause of premature death, yet fewer than 1 in 5 people have their blood pressure (BP) under control.¹⁵ In clinical terms, hypertension is defined as “the level of BP at which the benefits of treatment (either with lifestyle interventions or drugs) unequivocally outweigh the risks of treatment, as documented by clinical trials”.¹⁴ Guidelines from both America and Europe recommended lifestyle interventions and drug treatment strategies to lower BP.14,16 The goal is to reduce overall CV risk.^14,16 Studies have shown that just by lowering systolic BP by 10 mmHg or diastolic BP by 5 mmHg, significant reductions in all types of major CV outcomes can be achieved (i.e. death, stroke, coronary events and heart failure).¹⁴

The path less trodden: pulmonary arterial hypertension (PAH)

Not all cases of high blood pressure are the result of “normal” hypertension. One such exception is PAH, a rare, progressive, life-threatening disease.¹⁷ It is characterized by a sustained increase in pulmonary arterial pressure and pulmonary vascular resistance leading to right ventricular heart failure and premature death.¹⁷ PAH is incurable, and treatment is centered on symptomatic relief and prolonging survival.¹⁸

The journey can get congested near the end: thrombosis

The progressing stages of CVD can eventually lead to a thromboembolic event where blood clots block blood vessels, sometimes leading to death.^1,19 Thromboembolic conditions are divided into arterial conditions (ischemic heart disease, ischemic stroke) and venous conditions (deep vein thrombosis, pulmonary embolism).¹⁹ Arrhythmia is a major risk factor for both and the incidence of thrombosis increases with increasing age.¹⁹ Estimates suggest that thrombosis affects 115-269 per 100,000 people globally, but substantially fewer people are aware of this condition (44–54%) than they are of heart attacks and strokes (85–88%).¹⁹

Viatris: a heritage of support for every stage of the journey

Viatris^® has been committed to helping patients with CVD for almost 30 years.²⁰ During this time, Viatris has accrued 450 million patient years of experience producing the highest-quality medications with a complete portfolio of products for patients with CVD.²¹ Their wide portfolio extends across the CVD spectrum, from preclinical support to help reduce lifestyle risk factors to covering increasingly advanced conditions.

Viatris has consistently developed the scientific evidence for these products which are endorsed in the latest clinical guidelines developed by the main international experts and scientific societies in their respective fields:

• LIPITOR^® (atorvastatin) is one of two high-intensity statins currently available, and all clinical guidelines recommend high-intensity statins, or the highest tolerated statin dose, as first-line treatment for dyslipidemia and the primary prevention of CVD.^{7,12,13,22-24} LIPITOR^® is indicated to reduce the risk of a number of CV events (e.g., myocardial infarction, stroke). It is also indicated to reduce the risk of CV events in adult patients with type 2 diabetes with multiple risk factors and is the only statin indicated for the secondary prevention of coronary heart disease.²⁵
• CADUET^® (amlodipine/atorvastatin) is indicated in patients for whom treatment with both amlodipine and atorvastatin is appropriate. Amlodipine is indicated for the treatment of hypertension, to lower BP. Atorvastatin is indicated as an adjunct therapy to diet for prevention of CVD and hyperlipidemia.²⁶
• NORVASC^® (amlodipine) is recommended in all major international guidelines and is a first-line treatment for a wide range of hypertensive patients.^14,15,27-29 NORVASC^® provides 24-hour continuous BP reductions.^30-32