EUGLOREH project




5.2. Cardiovascular diseases

5.2.6. Future developments

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5.2.6. Future developments


In the last decade, innovations in diagnostic technologies in the cardiovascular field have facilitated diagnosis at earlier phases in the course of the natural history of the disease or in presence of less severe tissue damage. For instance, the use of new biomarkers, such as the routine introduction of new myocite damage markers (troponins), has changed the approach towards myocardial necrosis and brought to a review in the definition of AMI, while nosological and coding changes in international disease classification pose new challenges for the comparability of disease indicators. All these factors may have an influence in producing spurious trends of disease frequency, severity, prognosis and variations in medical practice, leading to wrong conclusions and decisions if not properly controlled with the adoption of updated and valid epidemiological methods (, 2007)

IHD is a complex disease that can be prevented through low-cost means, such as the reduction of risk factors or through more expensive treatments, such as invasive surgery. Innovations in medical, invasive and biological treatments contribute substantially to the escalating costs of health services. Therefore, we have an urgent need for reliable information on the magnitude and distribution of the problem for both adequate health planning and clinical decision making with correct cost-benefit assessments.

It is important to remember that risk factors such as smoking habit, cholesterol, blood pressure, obesity and physical inactivity play an important role in the aetiology of CVD. These factors are largely modifiable through lifestyle interventions. The great majority of cardiology studies suggests that improvements in treatment (thrombolysis; aspirin; angiotensin-converting-enzyme inhibitors; statins etc) explain less than half of the mortality decline; the major contribution to mortality decline comes from risk factors reduction.

One of the first steps is to reduce smoking among men and prevent increase among women as health benefits of smoking cessation occur faster for CVD than in other diseases. Therefore, policies that prevent and reduce smoking may bring immediate and large benefits for reducing mortality.

Nevertheless, it is important to rmember that all these policies, although important, would target only 20-30% of adult population.

Epidemiological data show that strategies to encourage people to adopt healthy diet and make physical activity are addressed to the overall population. The WHO European Action for Food and Nutrition Policy 2007-2012 (WHO, 2007) establishes health, nutrition, food safety and food security goals and provides a coherent set of integrated actions, spanning different government sectors and involving public and private actors, for Member States to consider in their own national policies and health system governance and for international organizations to consider at regional and global levels. Proposed actions include improving nutrition and food safety in early life, ensuring a safe, healthy and sustainable food supply, providing comprehensive information and education to consumers, integrating actions to address related determinants (such as physical activity, alcohol, water, environment), strengthening nutrition and food safety in the health sector, and monitoring and evaluating progress and outcomes.


Plasma cholesterol levels and CVD risk

Observational studies performed in the sixth decade of the last century showed that the average level of total plasma cholesterol in different countries is associated with the country specific mortality for Coronary Heart Disease (CHD) (Keys A et al, 1966). Subsequently, the existence of a continuous an graded association between plasma cholesterol levels and CHD risk was convincingly proven by a number of epidemiological studies (Stamler J et al, 1986). The association extends to values of plasma cholesterol well below those usually observed in developed countries (now around 200 mg/dL). The different roles of the various classes of cholesterol-carrying lipoproteins in blood in determining CVD risk was elucidated in the same years. Low Density Lipoprotein (LDL) levels are directly associated to CHD risk, while the High Density Lipoprotein (HDL) fraction have a negative (protective) association with CVD (Kannel WB, 1985). Randomized, placebo-controlled trials performed with various hypocholesterolemic drugs have definitively shown, starting from the mid80s, that total and LDL cholesterol reduction causes a reduction of CHD morbidity and mortality (Baigent C et al, 2005). The available information, more precisely, indicates that any reduction of plasma LDL cholesterol levels by 1% will induce within 5 years  a 1% reduction of CVD incidence (Robinson JG et al, 2006). The ischemic stroke risk was also diminished in many of these trials, even if the association of stroke with plasma cholesterol levels is weak, or absent, in most epidemiological studies (Lewington et al, 2007). From a mechanistic point of view, cholesterol reduction has been shown to slow atheroma progression, and/or induce regression, improve endothelial function and vasomotion, modulate the inflammatory responses involved in the atherosclerotic process and stabilize the atherosclerotic lesions. In our days, an improved knowledge of dietary interventions useful to control plasma cholesterol levels and the availability of drugs able to inhibit cholesterol synthesis and absorption makes it possible to reach the proper therapeutic target (plasma cholesterol levels ranging from 70 mg/dL in very high risk patients to 160 mg/dL in very low risk subjects) in the large majority of individuals considered for CVD prevention.


Blood pressure and CVD risk

Elevated blood pressure levels are associated with an increased risk of stroke, of CHD and of peripheral vascular disease (Kannel WB, 1996). The association is observed both in men and in women, at any age, starting from blood pressure levels of 115 mmHg of systolic blood pressure (SBP) and from 75 mmHg of diastolic blood pressure (DBP) (Lewington S et al, 2002). The CVD risk associated to blood pressure values around 130-139/85-89, largely prevalent in European countries, is about 2 times higher than the risk associated to blood pressure values < 120/80 mmHg (Vasan R et al, 2001). Also an isolated increase in SBP is associated to increased CVD risk, especially in elderly subjects (Weijenberg MP et al, 1996). A number of well performed randomized, placebo-controlled intervention trials, has shown that a reduction of blood pressure causes a reduction of fatal and non fatal CVD events. The reduction is larger for stroke events, while the reduction of coronary events is less large, but nevertheless statistically and clinically significant (Turnbull S et al, 2003). Lifestyle improvement interventions are associated to moderate but significant reductions of both SBP and DPB. The control of overweight, a reduction of sodium (salt) intake to less than 1,5 g (3,8 g) per day, an increased intake of fruit, vegetables, and an adequate level of physical activity can help to maintain blood pressure levels in the desired range (Sacks FM et al, 2001). If the result achieved is not sufficient, and especially if the overall CV risk of the patient considered is high, a pharmacological treatment should be considered. All the antihypertensive classes available for treatment can be used, taking into consideration the pharmacological differences among these compounds and the comorbidities which may be present in the patient. The association of two or more drugs is often necessary to achieve the desired goals (< 140/90 mmHg in the general population, and < 130/80, if feasible, in diabetic or patients with established CVD) (Graham I et al, 2007).


Focus Box References (missing references can be found in 5.2.7)

Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R; Cholesterol Treatment Trialists' (CTT) Collaborators (2005). Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366: 1267-1278.

Lewington S, Clarke R, Qizilbash N, Peto R, Collins R (2002): Prospective Studies Collaboration : Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360: 1903-1913.

Kannel WB (1985). Lipids, diabetes, and coronary heart disease: insights from the Framingham Study. Am Heart J 110: 1100-1107.

Kannel WB (1996). Blood pressure as a cardiovascular risk factor: prevention and treatment. JAMA 275: 1571-1576.

Keys A, Aravanis C, Blackburn HW, Van Buchem FS, Buzina R, Djordjević BD, Dontas AS, Fidanza F, Karvonen MJ, Kimura N, Lekos D, Monti M, Puddu V, Taylor HL (1966). Epidemiological studies related to coronary heart disease: characteristics of men aged 40-59 in seven countries. Acta Med Scand Suppl 460: 1-392.

Weijenberg MP, Feskens EJ, Kromhout D (1996). Blood pressure and isolated systolic hypertension and the risk of coronary heart disease and mortality in elderly men (the Zutphen Elderly Study). J Hypertens 14: 1159-1166.

Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R (2007): Prospective Studies Collaboration: Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 370: 1829-1839.

Robinson JG, Smith B, Maheshwari N, Schrott H (2005). Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J Am Coll Cardiol 46: 1855-1862.

Stamler J, Wentworth D, Neaton JD (1986). Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA 256: 2823-2828.

Turnbull F; Blood Pressure Lowering Treatment Trialists' Collaboration (2003). Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 362: 1527-1535.

Vasan RS, Larson MG, Leip EP, Evans JC, O'Donnell CJ, Kannel WB, Levy D (2001). Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med 345: 1291-1297.