Cross-sectional epidemiological study to evaluate the cardiovascular profile of a cohort of blood donors

Abstract

Background

Cardiovascular diseases are among the most frequent causes of mortality and morbidity in industrialised countries. The identification of subjects at high risk of cardiovascular diseases is one of the main aims of individual primary prevention programmes and is the essential background for instituting interventions aimed at reducing modifiable risk factors, from lifestyle changes to pharmacological interventions.

Donors and method

In order to evaluate the absolute global risk of cardiovascular disease in the population of blood donors of the Transfusion and Immunohaematology Centre of the Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena of Milan, we used the absolute global cardiovascular risk (CVR) score of the Progetto Cuore.

Between September 2004 and June 2006, 11,093 blood donors were evaluated for their suitability for donating blood. The criteria for inclusion in the calculation of the individual values of the absolute global CVR score were: age between 35 and 65 years old, fasted for at least 12 hours, and no previous reported or diagnosed cardiovascular episodes. Each donor was also asked to provide written informed consent to participation in the study.

The population of blood donors was divided into four groups according to their CVR score: CVR < 3%, CVR between 3% and 10%, CVR between 10% and 20%; CVR above 20%. The characteristics of the population were analysed subdividing the subjects according to age and gender.

Results

Although most of the blood donors belonged to the group with low CVR, it was nevertheless possible to identify a group of donors with high CVR.

Conclusions

It is to be hoped that CVR is calculated ever more widely in the population of blood donors in order to identify individuals at high CVR and also with the aim of reducing the levels of risk factors in the population with low or moderate CVR.

Introduction

Cardiovascular diseases are the most important causes of mortality and morbidity in industrialised countries: it is, therefore, essential to institute primary prevention programmes, both at an individual level and in the general population. Numerous published studies have identified various risk factors, which, particularly when present in combination, are responsible for the development of atherosclerosis: in fact, over 90% of patients who have had an acute myocardial infarct have at least one risk factor that could be modified by a change in lifestyle or by pharmacological treatment¹.

Nowadays it is no longer sufficient to consider separately the risk factors present in each subject. In fact, since the early 1990s, with the publication of the risk charts derived from the Framingham study^{2, 3}, the prevailing concept is that of evaluating an “absolute global risk” that expresses the probability of disease in the individual subject based on the co-existence of several risk factors^4–6.

To this end, a cardiocerebrovascular risk score has recently been defined, as part of the Progetto Cuore of the Italian National Institute of Health (NIH), for use in the Italian population. This score was derived from the results of an epidemiological cohort study^7–9. Although the guidelines indicate that the priority of a prevention programme should be given to identifying individuals with high cardiovascular risk, it is worth highlighting that about one-third of cardiovascular diseases develop in the subjects at low-moderate risk¹⁰. Therefore, in a long-term prevention strategy, it is important to extend interventions to the general population, in order to spread the concepts of health and identify a more “aggressive” and targeted preventive programme for the groups at high risk.

On this background, the Transfusion and Immunohaematology Centre of the Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena of Milan, in collaboration with the NIH, organised a programme to evaluate cardiovascular risk in our blood donors. These blood donors represent an “ideal” population for two reasons:

1. they constitute a population of “supposedly healthy” subjects who, like many other Italians, are rarely accustomed to undergo regular control examinations in the absence of symptoms or acute problems;

2. they are a numerically large sample (over 10,000 subjects) of people who periodically attend the same centre, allowing a long period of observation with homogeneous and centralised collection and analysis of their data.

The main aim of our study was to evaluate the cardiovascular profile of blood donors, using the score proposed by the Italian NIH, in order to identify early those subjects at risk of cardiovascular and cerebrovascular diseases.

Materials and methods

Subjects included in the study

The subjects considered eligible for enrolment in this study were all candidates for blood donation at our Centre, including both “new donors” and periodic donors, these latter defined as individuals who had donated blood at least twice in the preceding 2 years. In analogy with the NIH Progetto Cuore, the age range for participation in the programme was chosen to be from 35 to 65 years old. All the donors signed informed consent to inclusion in the programme. Exclusion criteria were lack of consent and a non-fasting state. The cardiological criteria for suitability for blood donation are listed in table I.

Table I.

Cardiological criteria for suitability for blood donation

- Systolic blood pressure > 110 mmHg < 160 mmHg - Diastolic blood pressure > 60 mmHg < 100 mmHg - Heart rate > 50 bpm < 100 bpm - Absence of current or past cardiovascular disorders

Data collection

Computerised clinical records, containing the history, clinical data and lifestyle habits of the subjects, were compiled for each individual.

Risk factors

The individual scores of global cardiovascular risk (CVR) were calculated using the algorithm generated by the Italian Progetto Cuore study by the NIH, which takes into account eight variables (age, sex, systolic blood pressure, total cholesterol, HDL cholesterol, glycaemia, smoking status and antihypertensive therapy).

The following criteria were used for each of the variables.

Arterial blood pressure: the value considered was the mean of two measurements made using a mercury sphygmomanometer on the right arm, with the patient sitting and having rested for at least 5 minutes.

Total and HDL cholesterol: the levels were determined on fresh blood samples taken from fasted subjects. The analyses were conducted in the Biochemistry Laboratory of the Centre using a colorimetric enzymatic method (Roche Diagnostics GmbH, Mannheim, Germany) for total cholesterol and the homogeneous colorimetric enzymatic method (Roche Diagnostics) for HDL cholesterol.

Glycaemia: blood sugar levels were measured on a venous blood sample taken from fasted subjects using the hexokinase method, with an Integra 800 analyser (Roche Diagnostics). A subject was considered diabetic if he or she had a level of glycaemia >126 mg/dL on two consecutive occasions or was taking anti-diabetic drugs.

Smoking status: donors who had smoked within the preceding 12 months were considered active smokers.

Antihypertensive treatment: regular use of antihypertensive treatment was recorded in the subjects’ clinical records.

It was not possible to evaluate cardiovascular risk for extreme values of the risk factors, that is for cholesterolaemia below 130 mg/dL or above 320 mg/ dL, for HDL cholesterol below 20 mg/dL or above 100 mg/dL and for systolic blood pressure below 90 mmHg or above 200 mmHg.

On the basis of the CVR score, the population was divided into four groups: low risk (<3%); moderate risk (3–10%); moderate-high risk (10–20%); high risk (>20%). Furthermore, to define the general characteristics of the population recruited into the study, the following parameters were recorded during the medical examination to assess the subjects’ suitability for blood donation:

• - heart rate at rest (beats per minute, bpm);

• - systolic and diastolic blood pressure;

• - body mass index (BMI = weight in Kg/height in m²), calculated from the weight and height measured with the person wearing light clothes.

The characteristics of the population are presented in table II.

Table II.

Variables used to evaluate risk

Variable	Men (n = 7,872)			Women (n = 3,221)			Total (n = 11,093)
	n	mean	s.d.	n.	mean	s.d.	n.	mean	s.d.
Age(years)	7,872	44.8	7.6	3,221	45.7	8.1	11,093	45.1	7.8
Systolic blood pressure (mmHg)	7,850	128.0	10.4	3,206	123,7	10.9	11,056	126.7	10.7
Diastolic blood pressure (mmHg)	7,853	83.3	6.3	3,209	80.1	6.2	11,062	82.4	6.4
Total CHL (mg/dL)	7,865	210.3	35.9	3,218	207.8	35.8	11,083	209.6	35.9
HDL-CHL (mg/dL)	7,846	53.7	12.1	3,206	69.0	14.7	11,052	58.1	14.7
BMI (kg/m2)	7,852	25.8	3.1	3,207	23.9	3.8	11,059	25.2	3.4
BMI (kg/m2) (Smokers)	1,792	25.9	3.1	757	23.5	3.6	2,549	25.2	3.4
BMI (kg/m2) (Non/Ex-smokers)	6,059	25.7	3.1	2,449	24.0	3.8	8,508	25.2	3.4
Glycaemia (mg/dL)	7,860	94.6	10.2	3,214	89.1	8.9	11,074	93.0	10.1
CVD risk at 10 years
< 3%	5,248	1.5	0.6	2,890	0.7	0.6	8,138	1.2	0.7
3–10%	2,136	5.2	1.8	176	4.5	1.5	2,312	5.2	1.8
10–20%	318	13.1	2.6	-	-	-	318	13.1	2.6
≥20%	23	23.3	3.0	-	-	-	23	23.3	3.0
All	7,725	3.1	3.1	3,066	0.9	1.1	10,791	2.5	2.9

Results

Between September 2004 and June 2006, CVR was evaluated in 11,093 blood donors. This population of blood donors was divided into the above described four groups (table III).

Table III.

Cardiovascular risk

Variable	Men (n = 7,872)		Women (n = 3,221)		Total (n = 11,093)
	n	%	n.	%	n.	%
Smoke	1,800	22.9	762	23.7	2,562	23.1
Diabetes	76	1.0	7	0.2	2,562	0.8
Antihypertensive treatment	707	9.0	186	5.8	893	8.1
Lipid-lowering therapy	147	1.9	46	1.4	193	1.7
CVD risk category
< 3%	5,248	67.9	2,890	94.3	8,138	75.4
3–10%	2,136	27.7	176	5.7	2,312	21.4
10–20%	318	4.1	0	0.0	318	2.9
≥20%	23	0.3	0	0.0	23	0.2
BP category based on SBP/DBP
Normal	2,633	33.5	1,783	55.6	4,416	39.9
Prehypertension	2,586	32.9	810	25.3	3,396	30.7
Hypertension - stage I	1,773	22.6	400	12.5	2,173	19.7
Hypertension – stage II or treated	858	10.9	213	6.6	1,071	9.7
BMI (3 categories)
≤24	2,919	37.2	2,115	65.9	5,034	45.5
25–29	4,098	52.2	815	25.4	4,913	44.4
≥30	835	10.6	277	8.6	1,112	10.1

The mean age of the subjects was 45.1 years (SD 7.8), with a higher proportion of males (males 7,872; females, 3,221). The percentage of smokers was high (about 23% in both sexes); more than 50% of the male donors were overweight (BMI >25). Although the mean blood pressure values were within the normality in about 40% of the subjects, as many as 30% were prehypertensive. Overall, 75.4% of the whole population were at low risk. There were only male donors in the moderate-high and high risk groups. The subjects at increased risk were referred for second level investigations, and, if needed, pharmacological treatment. Adhesion to the programme exceeded 95% and 6-monthly follow-up controls are planned for all subjects.

Discussion

The first risk chart published in the literature was that derived from the Framingham study, which had the limitation of overestimating risk when applied to Mediterranean populations¹¹. In 2003, the EUROSCORE was presented; this score, designed for European populations, considered the probability of fatal events¹².

More recently, an Italian score was derived from the Progetto Cuore, which drew on longitudinal studies on the Italian population. This score considers not only fatal cardiocerebrovascular events, but also disabling ones (e.g. strokes, infarcts).

Our study represents the first experience of a cardiovascular prevention programme based on the Italian risk score, applied to a large population of blood donors followed at a single centre. There are few data in the literature concerning the epidemiological characteristics of this population. On the basis of the criteria for suitability for blood donation, these are people at a lower risk of infectious diseases than the general population and overall are in “good health” at the time of the visit for the donation. It is not, however, known whether there is the same distribution of risk cardiovascular risk factors in donors, nor is the prevalence of major cardiovascular events in this population known.

Our project, although it is still underway, allows the following observations to be made:

1. blood donors are a population at low cardiovascular risk both because the presence of cardiovascular diseases is a contraindication to donation itself and because they undergo periodic controls;

2. the use of a risk score is an efficient instrument for involving the population to participate more actively in the maintenance of their own health;

3. early stratification has led to the prompt identification of subjects at greater risk, before they have developed overt disease.

Some limitations of the study should be acknowledged. First of all, this is a selected population, not completely representative of the overall Italian population; for example, the reduced percentage of females among the blood donors is a known occurrence, the cause being the lower iron reserves in women of childbearing age. Furthermore, in our study – as in general in all prevention studies – it was not possible to compare the efficacy of our preventive programme against that of a “placebo” strategy, since it would be unethical not to encourage the correction of clear risk conditions (e.g. smoking).

The next end-point of the study will be evaluate the trend in risk score over time, considering the score as an indicator of the efficacy of our prevention programme.

As indicated in the literature^{13, 14}, our results confirm the importance of using a calculation of absolute global risk in order to provide an effective and prompt cardiovascular prevention programme: this strategy has, in fact, enabled the early identification of people at high risk who are referred for specific management, from lifestyle changes to pharmacological treatment.

Conclusions

The possibility of calculating the CVR in blood donors provides the opportunity of carrying out cardiovascular screening in a population considered to be in good health. The calculation of the CVR also allows activation of preventive strategies: raising awareness in the population at high risk and referring them for more detailed cardiovascular assessment or targeted therapy and raising awareness in the population with moderate or low CVR, reducing these subjects’ exposure to the individual risk factors. Periodic evaluation of the absolute global CVR could, therefore, lead to a reduction in the long-term risk of this population. It is important to highlight that the population’s percentage of adhesion to prevention programmes associated with blood donation is high.