(C1) Classification, risk factors and epidemiology of cardiac disease in developed and developing countries

Cardiovascular disease is a class of diseases that involves the heart and the blood vessels.The disease is divided in different categories: congenital heart disease: damage of the heart existing since birth (cardiac malformations); valvolar heart disease: damage of one or more of the four valves of the heart; inflammatory heart disease:

o endocarditis: inflammation of the inner layer of the heart,o myocarditis: inflammation of the middle layer (muscular component) of the heart, o pericarditis: inflammation of the outer layer of the heart,o inflammatory cardiomegaly: increased heart dimension (as result of an inflammatory process);

rheumatic heart disease: damage of the heart (both heart muscle and heart valve) due to rheumatic fever, triggered by pathogenic organisms (such as streptococcus pyogenes);

hypertensive heart disease: damage of the heart secondary to hypertension; cardiac dysrhythmias: abnormalities of heart rhythm; cardiomyopathy: damage of cardiac muscle; heart failure: inability of the heart to pump blood in the body to such a rate that satisfy body request; pulmonary heart disease: failure at the right side of the heart with respiratory system involvement; coronary artery disease: damage of the blood vessel supplying blood to the heart; peripheral arterial disease: damage of the blood vessel supplying blood to the body; cerebrovascular disease: damage of blood vessels supplying blood to the brain (includes stroke).

Cancer and cardiac disease have been among the most common causes of death worldwide during the different time periods. In the old age, cancer deaths were more frequent than cardiovascular deaths; while in nowadays, cardiovascular deaths are more frequent than cancer deaths.

Cardiovascular disease, in the past a small cause of death worldwide (since before 1900 malnutrition and infectious diseases were the most common causes), is nowadays the most common cause of death worldwide. The global rise in cardiovascular diseases is the result of a transformation in the causes of morbidity and mortality during the twentieth and twenty-first centuries. Known as the epidemiologic transition, this shift is driven by industrialization, urbanization and lifestyle changes taking place in every part of the world among all races. The transition is divided into four basic stages:

In terms of economic development, the world can be divided into two broad categories: high-income countries and low-/middle-income countries. Currently, 25% of the world’s population lives in high-income countries, while 75% of the world’s population lives in low-/middle-income countries; the former once are those countries driving the rates of change in the global burden of cardiovascular diseases. At the present time cardiovascular diseases accounts for approximately 30% of deaths worldwide: 40% in high-income countries, 28% in low-/middle-income countries. Cardiovascular disease death, as a percentage of all deaths in different regions and total regional population, is: 38.5%: North America, Western Europe, Oceania (high income areas); 27.8%: Central America, South America; 38.5%: Eastern Europe, Central Asia; 58.1%: Eastern Asia and Pacific; 25.2%: South Asia; 25%: North Africa; 9.7%: Sub-Saharan Africa (low income areas).

The global variation in cardiovascular disease rates is related to specific risk factors: constitutional risk factors:

o genetic predisposition,o age (older than 55 for men, 65 for women),o gender,o race;

metabolic risk factors:o diabetes mellitus,o lipids levels,o dyslipidemia,o obesity (body mass index ≥30 kg/m2),o microalbuminuria (or estimated GFR <60 ml/min),o hypertension;

behavioural risk factors:o education,o diet, o physical inactivity, o tobacco.

The risk factors study for cardiovascular diseases was conducted in Framingham, reason why the study regarding cardiovascular disease risk factors took the name of Framingham study (1948/2008).

Framingham heart study is a long term ongoing cardiovascular study on residents of the town Framingham (MA). This population-based family study, now on its third generation of participants, provides the information necessary to the understanding of the hypertensive and atherosclerotic heart disease; prior to this study almost nothing was known about it. first generation study: original cohort (1948-2008)

o n=5209 men and women,o 1644 spouse pairs, o 596 extended families;

second generation study: offspring (1978-2002)o n=5124 men and women (ages 5-70),o 1576 spouse pairs, o 3514 biological offspring;

third generation study (2002-),o n=3500 men and women.

Progression of cardiovascular disease

Hypertension is the most common risk factor for CVD in Western Countries, estimated to affect more than 35% of the population. Only in the United States, 35 million diagnosis of hypertension at medical visits, 50 million or more Americans have high blood pressure and 7.1 million deaths per year may be attributable to this disease.

Figure 1Distribution of blood pressure in adults in the United StatesFigure 2Mortality due to CHD per quartile of systolic blood pressure

Hypertension prevalence is a risk factor for stroke incidence. The incidence of the disease is highly heterogeneous; for example, in Western Europe countries there is a trend toward a decrease in stroke incidence, while in Eastern Europe countries there is an increase in stroke incidence.Prevention of the risk factors for the disease is meant to prevent the onset of heart disease. Only a small fraction of the hypertensive population has an elevation of blood pressure alone with no other risk factor, while the majority exhibits additional cardiovascular risk factors able to trigger the onset of the disease.Evidence that, in high-risk individuals, blood pressure control is more difficult and more frequently requires the combination of antihypertensive drugs with other therapies, such as aggressive lipid-lowering treatments,Systematic COronary Risk Evaluation (SCORE) model has been developed based on large European cohort studies to the risk of dying from cardiovascular disease over 10 years based on age, gender, systolic blood pressure, total cholesterol and smoking habits.

The stages of intervention in cardiovascular diseases are: primordial intervention: before risk factors develop, primary intervention: treatment of risk factors, secondary intervention: after a cardiovascular disease event occurs.

Primordial prevention, introduced by Strasser, is the stage of intervention in cardiovascular diseases based on the preclusion of risk factors for the disease from developing. It highlights the importance of inhibiting the onset of the disease on the beginning, since once a risk factor has developed, lifestyle interventions and medication to control the disease can certainly prevent events such as stroke and myocardial infarction, but they do not reduce cardiovascular disease events to levels seen in those who maintain optimal risk factor profiles into middle and older ages. As a matter of fact, Donald Lloyd-Jones that studied the positive benefits of maintaining a positive risk factor profile into middle age, was the first who stated that, “Medications and lifestyle interventions cannot reduce cardiovascular disease event rates to levels seen in those who maintain optimal risk factor profiles into middle and older ages.”Even for your normotensive patients, it is extremely important to provide advice about lifestyle interventions to prevent the development of hypertension.

Geoffrey Rose noted that prevention can focus on unhealthy individuals or unhealthy populations. The majority of cardiovascular disease events occur in a large population with average or only mildly elevated levels of risk factors, rather than in a small population with significantly elevated risk factors. Population strategies can be used to shift the population distribution of risk factors toward more favorable levels. With successful population strategies, small changes can result in large improvements in disease rates. In his book, “The strategy of preventive medicine”, he sets out the case that the essential determinants of the health of society are to be found in its mass characteristics. The deviant minority can only be understood when seen in its societal context, and effective prevention requires changes which involve the population as a whole.Population-wide strategies will also support lifestyle modification in those at high risk. The extent to which one strategy is emphasized over the other depends on achievable effectiveness, cost-effectiveness and resource considerations. A population strategy of prevention is necessary where risk is widely diffused through the whole population.

Between 1980 and 2000 there has been a decrease (over 340,000 fewer deaths) in coronary heart disease due to both changes in risk factors and improvements in treatment. Over time there has been a worsening in some risk factors (such as diabetes and obesity) and an improvement in some risk factors (such as cholesterol, blood pressure, activity physical and smoking).Overall, in this context, a decrease in population blood pressure was responsible for 20% of this decrease in coronary heart disease deaths; as result of the fact that during this period, the awareness of hypertension increased from 51% to 69%.

A meta-analysis of multiple cohort studies from the US reinforced the tremendous benefit of lowering blood pressure in preventing stroke and myocardial infarction at the patient level.A 10mmHg lower systolic blood pressure or 5mmHg lower diastolic blood pressure is associated with an approximately 20–25% lower risk of coronary heart disease and an approximately 40% lower risk of stroke.

Only 46% of adults with hypertension had adequately controlled blood pressure: adults aged 18-39 are less controlled than older age groups, the rates of control for males is less than females, Blacks and Hispanic falls below that of Whites.The Million Hearts initiative has set a goal of 65% control by 2017 overall, and 70% in the clinical setting.

Treatment of the disease relay on: lower risk factors, lifestyle modifications, drug therapies.

Life style modification: adopt DASH eating plan (for dietary sodium reduction); moderation of alcohol consumption; physical activity; weight reduction:

Sodium intake is one of several dietary factors that contribute to increased blood pressure. Of all the dietary factors impacting blood pressure, sodium intake is one not under our control given that the majority of sodium has already been added to packaged and processed food. Sodium is the principal cation of the extracellular fluid, functioning as the osmotic determinant in regulating extracellular fluid volume and plasma volume. Once it inside this compartments it is controlled by the kidneys which regulates body sodium concentration by clearing excess sodium through urine.It is estimated that reducing salt intake by 6g a day could lead to a 24% reduction in deaths from strokes and an 18% reduction in deaths from coronary heart disease, thus preventing approximately 2.6 million stroke and heart attack deaths each year worldwide.

When looking at the Dietary Approaches to Stop Hypertension (DASH) Trial and the DASH Sodium Trial, improving dietary patterns can help reduce blood pressure, but greater effects are seen when an improvement in dietary pattern is coupled with sodium reduction. Dietary Approaches to Stop Hypertension (DASH) Trial ccompared the effects of three diets: typical

American diet, fruits and vegetable diet, and a diet rich in fruits and vegetables with low fat dairy (reduced in saturated fat, reduced total fat, and reduced cholesterol); in this context, all diets provided about 3,000 mg sodium per day. Combination diet (DASH) produced the largest blood pressure reduction after 8 weeks, average decrease of 5.5-3.0 mm Hg. The potassium, magnesium, and calcium levels were close to the 25th percentile of U.S. consumption, and the macronutrient profile and fiber content corresponded to average consumption.

DASH Sodium Trial:o DASH diet and three levels of sodium intake: 1,150 mg, 2,300 mg, and 3,450 mg;o DASH diet and a low level of sodium: decreased SBP by 7.1 mg Hg. Participants with HTN

experienced a BP ↓ of 11.5 mm HgDiet, though, is of extreme importance in kidney diseases treatment: we eat 170 mmol of salt each day, although the recommendation for healthy individuals is to halve this quantity.

There are 10 food category contributors to sodium intake. Excluding the salt added at the table, 44% of US sodium intake comes from just these ten types of foods: meat, cheese, pizza, pasta mixed dishes, bread and rolls, sandwiches, cold cuts fresh and processed poultry, mixed dishes savory snacks, and soups, comprise the top 10 food category contributors to sodium intake. Some contributors like bread and poultry, may not taste salty, but because we consume a lot, they add up.

77%

12%6%5%

Processed and restaurant foodsNaturally occur-ringWhile eatingHome cook-ing

JNC VII medication recommendations are: stage 1 hypertension: thiazide-type diuretics, BB, CCB ACEi or ARB,; stage 2 hypertension: thiazide-type diuretic, BB, CCB, ACEi, ARB or combination of these drugs.

Treatment benefits: stroke incidence reductions: averaging 35-40%, MI reductions: averaging 20-25%, HF reductions: averaging >50%.

The number of heart transplants in Italy has greatly decreased because: prevention, decrease availability of donors, use of artificial devices.

The mortality of the cardiovascular disease is decreasing because of the new treatments.The majority of deaths related to the disease are due to coronary artery disease and diseases of the artery.

During studies, the trail population (young, male, white, healthy individuals) is quite different from the general population. In the general population the number of comorbidities has increased due to an improvement of the diagnosis, therefore it is important to be sure that the drug subministrated is treating heart failure and doesn’t interfere with the comorbidities.

Heart failure’s prevalence is related to age and gender. 15 millions of people living in Europe are estimated to be affected by heart failure, meaning 1/6.In the last 6 months of their life patients with heart failure undergo frequent hospitalization and spend a huge amount of money on their treatment.

years

expenses