8
Vascular risk screening: possible or too much, too soon? Background Cardiovascular disease accounts for 36% of mortal- ity and 20% of hospital admissions in the UK. It has long been known that environmental factors comprise the bulk of cardiovascular disease risk and thus that screening for cardiovascular disease may be desirable. The InterHEART study con- firmed that 90% of population attributable risk could be ascribed to lipids, hyper- tension, smoking, central obesity, diabetes, plus poor diet, lack of exercise and psychosocial factors (1). Over the years, there has been a welcome decline in the rates of cardiovascular disease that has been because of environment and life- style changes rather than any spe- cific medical intervention. Rates of cardiovascular disease started to decline in the 1950–1960s and then accelerated as air pollution reduced because coal-fired heating was replaced by cleaner fuels, rates of smoking fell and pharmaceutical intervention became more com- mon, with initially aspirin and later beta-blockers and finally angioten- sin-converting enzyme inhibitors and statins (2–4). In the UK, the implementation of the National Service Framework for Coronary Heart Disease (NSF- CHD) (5) further accelerated the fall when it was implemented through the primary care Quality Outcomes Framework, and the National Health Service (NHS) targets were achieved 2 years early. Yet, as noted in the official review of the NSF, most of the inter- ventions that were implemented involved high-risk groups (i.e. patients with established cardio- vascular disease), while little had been carried out in primary pre- vention or to address high rates of disease in deprived and immigrant populations (6). It is an unfortu- nate truth that 30–50% of patients experience their first vascular event as their last, so ideally intervention needs to be targeted in patients prior to the presence of overt disease, i.e. primary prevention. This has been recog- nised and made an official priority through the national screening strategy (cardiovascular) (7). The challenge remains how to do this affordably even if the overall health economics is favourable at a cost of £20k life year saved. Extensive epidemiological data has identified the envi- ronmental risk factors responsible for 90% of population attributable risk for coronary heart disease. These studies have identified age, gender, smoking, diabetes, hyperten- sion and hyperlipidaemia as contributory factors and allowed cardiovascular risk calculators to be developed. With the availability of effective interventions, there is an increasing focus on reducing cardiovascular disease through early case identification by screening. However, cardiovascular risk estimation is an imprecise art better suited to exclude patients from treatment than the unequivocal identification of high-risk individuals and subject to numerous confounding factors. The impreci- sion of risk calculators and the need to add additional specific or novel risk factors have led to increased com- plexity and sensitivity at the expense of specificity. It may be necessary to add more specific secondary bio- markers or imaging methods to truly identify high-risk individuals. Even after identification, the issue of accept- ability of long-term treatment for an asymptomatic con- dition remains, and there are concerns about adherence to therapy. Trials of screening allied with multiple risk factor intervention on cardiovascular events are dated; although many suggest small benefits, overall the results were disappointing. More modern studies have been small scale or only focused on surrogate markers. Large scale cardiovascular end-point trials of screening inter- vention are required to confirm the benefits of vascular risk screening. The focus on screening for high-risk indi- viduals should not obscure the need to reduce risk fac- tor burdens in the whole population through public health interventions. PERSPECTIVE ª 2009 Blackwell Publishing Ltd Int J Clin Pract, July 2009, 63, 7, 989–996 doi: 10.1111/j.1742-1241.2009.02111.x 989 30–50% of patients experience their first vascular event as their last

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Page 1: Vascular risk screening: possible or too much, too soon?

Vascular risk screening: possible or too much, too soon?

Background

Cardiovascular disease accounts for 36% of mortal-

ity and 20% of hospital admissions in the UK. It

has long been known that environmental factors

comprise the bulk of cardiovascular disease risk

and thus that screening for cardiovascular disease

may be desirable. The InterHEART study con-

firmed that 90% of population attributable risk

could be ascribed to lipids, hyper-

tension, smoking, central obesity,

diabetes, plus poor diet, lack of

exercise and psychosocial factors

(1). Over the years, there has been

a welcome decline in the rates of

cardiovascular disease that has been

because of environment and life-

style changes rather than any spe-

cific medical intervention. Rates of

cardiovascular disease started to

decline in the 1950–1960s and then

accelerated as air pollution reduced

because coal-fired heating was

replaced by cleaner fuels, rates of

smoking fell and pharmaceutical

intervention became more com-

mon, with initially aspirin and later

beta-blockers and finally angioten-

sin-converting enzyme inhibitors

and statins (2–4).

In the UK, the implementation of

the National Service Framework

for Coronary Heart Disease (NSF-

CHD) (5) further accelerated the

fall when it was implemented

through the primary care Quality

Outcomes Framework, and the

National Health Service (NHS)

targets were achieved 2 years early.

Yet, as noted in the official review

of the NSF, most of the inter-

ventions that were implemented

involved high-risk groups (i.e.

patients with established cardio-

vascular disease), while little had

been carried out in primary pre-

vention or to address high rates of

disease in deprived and immigrant

populations (6). It is an unfortu-

nate truth that 30–50% of patients

experience their first vascular

event as their last, so ideally intervention needs to be

targeted in patients prior to the presence of overt

disease, i.e. primary prevention. This has been recog-

nised and made an official priority through the

national screening strategy (cardiovascular) (7). The

challenge remains how to do this affordably even if

the overall health economics is favourable at a cost

of £20k ⁄ life year saved.

Extensive epidemiological data has identified the envi-

ronmental risk factors responsible for 90% of population

attributable risk for coronary heart disease. These studies

have identified age, gender, smoking, diabetes, hyperten-

sion and hyperlipidaemia as contributory factors and

allowed cardiovascular risk calculators to be developed.

With the availability of effective interventions, there is

an increasing focus on reducing cardiovascular disease

through early case identification by screening. However,

cardiovascular risk estimation is an imprecise art better

suited to exclude patients from treatment than the

unequivocal identification of high-risk individuals and

subject to numerous confounding factors. The impreci-

sion of risk calculators and the need to add additional

specific or novel risk factors have led to increased com-

plexity and sensitivity at the expense of specificity. It

may be necessary to add more specific secondary bio-

markers or imaging methods to truly identify high-risk

individuals. Even after identification, the issue of accept-

ability of long-term treatment for an asymptomatic con-

dition remains, and there are concerns about adherence

to therapy. Trials of screening allied with multiple risk

factor intervention on cardiovascular events are dated;

although many suggest small benefits, overall the results

were disappointing. More modern studies have been

small scale or only focused on surrogate markers. Large

scale cardiovascular end-point trials of screening inter-

vention are required to confirm the benefits of vascular

risk screening. The focus on screening for high-risk indi-

viduals should not obscure the need to reduce risk fac-

tor burdens in the whole population through public

health interventions.

PERSPECT IVE

ª 2009 Blackwell Publishing Ltd Int J Clin Pract, July 2009, 63, 7, 989–996doi: 10.1111/j.1742-1241.2009.02111.x 989

30–50% of

patients

experience

their first

vascular

event as their

last

Page 2: Vascular risk screening: possible or too much, too soon?

Problems with cardiovascular riskscreening

There are two major problems with vascular screen-

ing. First, many of the risk factors are asymptomatic,

thus leading to a natural reluctance for potential

beneficiaries to present for screening or to continue

with therapy. The disappointing results of the Multi-

ple Risk Factor Intervention Study (MRFIT) (8)

proved that even in a well-motivated population,

after 7 years lifestyle measures, although accepted,

were not implemented and thus had no effect on

cardiovascular events. A decade later, similar results

were found for nurse-based intervention in the

OXCHECK study, which showed only a theoretical

benefit on cardiovascular disease (CVD) risk (relative

12% reduction in Framingham risk) (9). Thus, the

only effective intervention in a short time horizon

(within and not between generations) is drug ther-

apy.

For one major risk factor (tobacco addiction), the

only moderately successful treatment is a short-term

drug therapy – varenicline (10,11). Other factors

require long-term therapy: there are data showing

the efficacy of aspirin in primary prevention in both

men and older women (12), antihypertensive therapy

even in prehypertension (130 ⁄ 80 mmHg at age

40 years) (13) and statins in high (14), intermediate

(15) and low (16) risk populations. Thus, evidence

exists for the drug therapies required to treat high

CVD risk successfully once it has been identified.

The concept of blanket treatment for multiple risk

factors using a poly-pill has been advocated (17).

Yet, in this cynical age, concerns remain that the

benefits of drug therapy do not exceed the risks from

side effects and, especially for older off-patent drugs

combined in a poly-pill.

Cardiovascular risk screeningalgorithms

The greatest risk factor for atherosclerotic disease is

age, and therefore it will always trump other factors

in any analysis. However, identification of patients at

risk of atherosclerosis means that individuals must

be identified at a stage when only their relative risk

is increased. As no single risk factor shows a totally

definitive association with increased CVD risk, all

protocols rely on cardiovascular risk estimation algo-

rithms. The concept is that individual risk can be

derived from population studies using systematic

epidemiological methods and exponential risk equa-

tions (18). The oldest and best established of these is

the Framingham equation from 1991 (19), which is

still used in the UK as the basis of risk screening

even though it over-predicts CVD events by 30%.

Other risk scores have been derived from European

populations (Munster Heart Study) (20) or based on

World Health Organisation MONICA cohorts (21)

or analysis of national disease registers (22,23)

(Table 1). However, even self-defined reporting of

cardiovascular risk factors can be used satisfactorily

to identify patients at high cardiovascular risk (24).

The Framingham risk function has been developed

over the years into variants to determine the risk of

stroke, those which include low density lipoprotein

(LDL) cholesterol or glucose and one to determine

lifetime risk (18,25). The last concept is particularly

relevant. Analysis shows that individuals with fewer

than three risk factors at age 50 years have a minimal

chance (5% men; 8% women) of developing CVD

before their time of death (26). This finding dupli-

cates an identical result from the Multiple Risk Fac-

tor Intervention Trial and Nurses’ Heart Studies, but

unfortunately all too few individuals (< 5%) have

the correct risk-free profile to reduce their risks by

69–82% over 30 years (27,28). All of these studies

include large numbers of patients but have relatively

few events, so the statistical power of such risk pre-

diction algorithms is to rule out future disease, but

unfortunately they are often used in reverse to rule

individuals into therapy, as can be seen from any

national guidelines statement.

Over the years, the pressure to treat at lower risk

thresholds has been driven by recruitment of pro-

gressively lower risk population to drug studies,

which has led guideline committees to progressively

reduce the acceptable risk threshold. In the UK, this

has fallen from 30% ⁄ decade for coronary heart dis-

ease (CHD) (40–45% for CVD) to 20% cardiovascu-

lar disease (15% CHD risk ⁄ decade) between the

publication of the Joint British Societies guideline in

1998 (29) and the revised version in 2005 (30).

Although this gave a significant increase in sensitiv-

ity, it is bought at the cost of a major reduction

in specificity. Further complications are added when,

in good faith, risk factors that were not significant in

the original analyses are added back to deal with spe-

cific problems. Thus increments are added to risk

calculations to account for obesity, family history of

CHD (31) or ethnicity (32) but not in any consistent

manner between guidelines.

Over time, risk factor definitions and analytical

methods have changed. Thus, diabetes has now been

redefined at lower glucose levels and then excluded

altogether from the risk calculation; now it has

become clear that the Framingham risk calculator is

fundamentally flawed for this group where CVD risk

approximates that of normoglycaemic patients with

prior CHD because it grossly under-predicts risk in

The pressure

to treat at

lower risk

thresholds has

been driven by

recruitment of

progressively

lower risk

population to

drug studies

ª 2009 Blackwell Publishing Ltd Int J Clin Pract, July 2009, 63, 7, 989–996

990 Perspective

Page 3: Vascular risk screening: possible or too much, too soon?

diabetes (33). The removal of diabetes from the risk

calculator has not been modelled, but given the

original data another factor would likely appear to

take its place – potentially body mass index or waist

circumference (34). Similarly, methods for mea-

suring lipids have changed: the reliability of high

density lipoprotein cholesterol (HDL-C) assays has

improved, but the consequences of these improve-

ments on risk screening have not been addressed and

the ‘standard’ method comparisons that would nor-

mally be carried out in routine pathology depart-

ments have not been performed satisfactorily (35).

The original manganese dextran assay for HDL-

cholesterol used in Framingham was subject to inter-

ference by triglycerides and was sensitive to collection

container levels of ethylene diamine-tetra-acetic acid

(EDTA) (the reference specimen type for determina-

tion of lipids). Modern methods using serum-separa-

tor tubes and a variety of techniques to precipitate

triglyceride-rich and LDL particles report higher

HDL-C levels with the bias ranging from 10 to 25%

(36). The effect of this is to significantly blunt the

risk attributable to lipids as the denominator in the

total cholesterol : HDL ratio is reduced.

The switch from mercury sphygmomanometer to

aneroid blood pressure measurement techniques

and the change in Korotkov sound phase also raise

problems of bias in the equations even if the meth-

ods are supposedly matched (37), Consequently,

Deming regression-correction term should be intro-

duced into the risk calculators and appropriate large

well distributed large samples used (38). Addition-

ally, the statistics behind the calculators assume that

all risk factors are independent. Given the clustering

of risk factors in the metabolic syndrome, the

assumption of independence is false meaning that

alternative statistical methods, perhaps factor analy-

sis, would be a preferable statistical technique to

identify key variables if there were any consensus

about how to do it.

The problems of risk factor redefinition and

uncontrolled assay modification pale into significance

when a closer view is taken of CVD risk equations.

All of the equations rely on exponents for individual

risk factors, and each exponent has a confidence

interval. Additionally, each measurement is subject

to recording bias and biological variation. Thus, ages

are approximated to 1 year (2.5% difference per year

at age 40 years); blood pressure measurements often

show digit bias and lipid and blood pressure mea-

surements also show a > 10% daily variation. Even

assuming a perfect statistical relationship to derive

the exponents, this leads to the 95% confidence

interval for risk for patients with a ‘true’ CVD risk

Table 1 Comparison of baseline variables required for CHD risk assessment

Risk factor

Framingham

PROCAM (20) SCORE (67) QRISK-2 (23)

Reynolds

(68,69) UKPDS (70)1991 (19) 1999 (71) 2007 (72)

Age Y (30–75) Y (30–75) Y (30–75) Y (35–65) Y (40–65) Y (35–75) Y (50–80) Y (25–65)

Gender Y Y Y Y Y Y Y Y

Smoking Y Y Y Y Y Y Y Y

SBP Y Y Y; BP treatment

added

Y Y Y; BP treatment

added

Y Y

LVH (ECG) Y N N N N N N N

DM Y Y Y Y N ⁄ A Y BMI added N ⁄ A Specific for NIDDM

Glycaemia (HbA1c)

eGFR N N N N N Chronic disease N N

TC : HDL Y Y Y HDL only Y Y Y Y

TG N N N Y N N N N

LDL-C N N N Y N N N N

CRP N N N N N N Y N

Family history

CHD

N (UK- post hoc) N N Y (< 65 years) N N Y (< 60 years) N

Ethnicity N (UK- post hoc) N (post hoc) N (post hoc) N (post hoc-

specific set)

N Integrated N Integrated

Deprivation N N N N N Y N N

Validation NHANES, WOSCOPS N N N N UK GP database N N

CRP, C-reactive protein – high sensitivity; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; LVH, left ventricular hypertrophy; NHANES, National

Health and Nutrition Survey; SBP, systolic blood pressure; TC, total; cholesterol; TG, triglycerides; WOSCOPS, West of Scotland coronary outcomes prevention study.

Type 2 diabetes is added as a variable in many calculators although this is not applied in practice.

ª 2009 Blackwell Publishing Ltd Int J Clin Pract, July 2009, 63, 7, 989–996

Perspective 991

Page 4: Vascular risk screening: possible or too much, too soon?

of 20% being 14–26%, based on a typical single

determination of risk factors (39). Increasing the

number of measurements to three only reduces this

confidence interval to 16–24%.

Another misconception is that adding risk factors

adds to specificity, but it actually increases error faster,

leading to apparently increased sensitivity but signifi-

cantly reduced specificity. For logistical reasons, many

guidelines recommend the use of posttreatment blood

pressures (not validated in Framingham except for

stroke) or suggest even simpler stratification tech-

niques based on prior risk factor identification. Unfor-

tunately, risk calculation equations are not

commutative and even minor deviations using prior

classifications can lead to many patients being incor-

rectly assigned (40). Therefore, despite the appearance

of a strong scientific foundation, risk calculation is a

complex tool that needs to be used carefully.

The practicalities of screening

Many guidelines recommend that cardiovascular risk

screening should be conducted using a battery of risk

factors including demographics, blood pressure, lip-

ids, glucose, renal dysfunction and obesity in patients

aged > 40 years. If risk assessment is performed sys-

tematically, then 18% have identified CHD, risk

equivalents or have been already treated, 22–78% of

men and 6–74% of women have a CVD risk

> 20% ⁄ decade in the 10-year age ranges from 40 to

80 years (Figure 1) (41). However, they do not con-

sider the cost of such an approach given that the

likely expenditure for such screening is at least

£23.70 ⁄ patient (7). This may be cost effective in the

long-term, but is of no help in a financially chal-

lenged climate, as it implies a cost of millions of

pounds for each Primary Care Trust. An alternative

cheaper approach has to be found.

The first principle that can be used is the Bayesian

one of prior risk. Registers already exist for patients

with established disease. Age is the greatest risk fac-

tor and a vascular risk policy involves selection of an

age group to target. Patients with risk factors

identified as a result of opportunistic screening or

self-reported risk factors represent preexisting

investments (42) or simple additional data gathering

(24). Initial approaches should target the more

elderly people and then move on to younger age

groups (42). Patients with a family history of early

coronary heart disease or stroke also have a raised

prior probability with the effect increasing risk by

1.5–2.8-fold depending on the definition used (43),

and this approach would start to identify patients

with genetic hyperlipidaemias as well as other possi-

ble inflammatory causes of CVD. In addition, many

patients with early CHD have dyslipidaemia as an

underlying cause (44). Many cardiovascular risk fac-

tors cluster in the metabolic syndrome, and it is

notable that six of the nine risk factors in Inter-

HEART relate to this complex [diabetes, total choles-

terol : HDL ratio; central obesity, hypertension, low

levels of exercise and poor diet (low fruit and vegeta-

ble intake)] (1). Thus, identification of patients with

the metabolic syndrome or its components will raise

the chance of identifying patients with CVD. As the

metabolic syndrome is a better predictor of future

risk of diabetes than cardiovascular disease (45),

especially if the International Diabetes Federation

definition is used, this strategy will also identify

patients with a high risk of diabetes, a cardiovascular

0

10

20

30

40

50

60

70

80

18 – 29 30 – 39 40 – 49Age (years)

Pre

vela

nce

(%

)

Men 10 – 20% Men > 20% Women 10 – 20% Women > 20%

50 – 59 60 – 69 70 – 79 > 80

Figure 1 Prevalence of patients with differing degrees of vascular risk from the HEART-UK Unilever cardiovascular

screening study (41)

ª 2009 Blackwell Publishing Ltd Int J Clin Pract, July 2009, 63, 7, 989–996

992 Perspective

Page 5: Vascular risk screening: possible or too much, too soon?

risk equivalent, and thus future CVD. It can also be

used to identify patients at future risk of hyperten-

sion if a family history of hypertension is available

(46). As not all obese patients display the metabolic

abnormalities of the metabolic syndrome (47),

maybe a metabolic syndrome score would be a better

input into the risk equations. It may be that as a

result of their reduced variance, chronic measures of

insulin resistance such as sex hormone binding glob-

ulin or long-term dysglycaemia such as HbA1c may

be better than the homeostasis index (HOMA),

which is based on highly variable measurement of

insulin and glucose. Studies of risk of diabetes or

cardiovascular disease suggest that models based

on age, gender, body mass index, family history of

diabetes and ethnicity with the addition of blood

glucose may have promise as simple methods of

approximation (48,49).

Looking for patients already identified by opportu-

nistic methods in primary care databases is likely to

yield a disproportionate number of future cases of

CVD (42). Thus, the priorities ought to be older

patients, men, those with obesity or hypertension

or those living in areas of deprivation. Based on

primary care data and modelled in the National

Institute for Health and Clinical Excellence guide-

line for lipid modification, this approach has been

proposed and found to be cost effective (50). The

main problem is that this neglects the 55% of risk

attributable to dyslipidaemia, but it should be noted

that at least some of the risks identified as being

because of lipids relate to low HDL-cholesterol,

which has a prevalence of 25% in primary preven-

tion populations and forms part of the metabolic

syndrome (51,52). In a risk algorithm derived from

the National Health and Nutrition Evaluation Survey

(NHANES), lipids and body mass index are inter-

changeable which is intriguing, especially given the

removal of diabetes from the Framingham algorithm

as currently applied (53). The efficacy of these strate-

gies is confirmed by the C-statistics of 0.78–0.83

on receiver–operator characteristic analysis although

concordances for identification are not stated (40).

It would appear therefore that the optimal strategy

would be to determine and record the following risk

factors:

• Age

• Gender

• Smoking

• Body mass index (or waist circumference)

• Blood pressure

• Family history of CVD prior to age 65 years

• Family history of diabetes

• Family history of hypertension

Opportunistic use could be made of previously

measured data on lipids and glucose or other risk

factors in any risk calculation. In patients with a

family history of early CHD, then risk testing for

cholesterol to identify potential cases of familial

hyperlipidaemia is warranted (44). The primary

objective of risk calculation would be to exclude

patients not requiring detailed review as methods

have a 90% negative predictive value (53). At a 15%

threshold (to allow for variances), this would likely

exclude 50–80% of men and 75–95% of women at

ages 40–60 years (41). It would also be a predomi-

nantly data-based exercise or only require brief cor-

respondence rather than formal clinical assessment

visits. These patients could be reassured that their

risk was likely to be low. In patients identified as

moderate risk (> 15%), the second stage would be to

conduct a more formal risk assessment including

biochemical analyses. For practical purposes, the fol-

lowing tests would give the best data:

• Total cholesterol : HDL ratio (non-fasting)

• Glucose (non-fasting)

• Creatinine

The cholesterol ratio shows a < 10% effect because

of fasting, while measurement of postprandial glyca-

emia is a better index for exclusion of frank diabetes,

as it captures the fraction of patients with a normal

fasting glucose but abnormal postprandial metabolism

in whom more specific tests should be conducted (54).

As blood pressure is already being measured and a low

estimated glomerular filtration rate (eGFR) is an inde-

pendent risk factor, the identification of higher risk

groups with early stages of renal dysfunction would

allow better targeting of therapy and might substitute

for the lack of measurement of electrocardiographical

evidence of target organ damage as recommended in

the original Framingham algorithm (55). Again the

principle is to exclude patients with risk < 15%. The

effectiveness of such a two-stage screening strategy has

never been modelled but may exclude another 10%.

The remaining individuals would be enriched in those

of high cardiovascular risk (> 20%) in whom defini-

tive tests are necessary. At the simplest level, this

involves fasting blood samples to repeat the factors

listed above, but it is well known that the risk algo-

rithms over-identify patients at potential risk. Consid-

eration should therefore be given to other methods of

risk stratification if these prove cost effective.

Further risk stratification strategies

The choices for tertiary risk stratification are varied. At

the simplest, the candidate indices include deprivation

Despite the

appearance of

a strong

scientific

foundation,

risk calculation

is a complex

tool that needs

to be used

carefully

ª 2009 Blackwell Publishing Ltd Int J Clin Pract, July 2009, 63, 7, 989–996

Perspective 993

Page 6: Vascular risk screening: possible or too much, too soon?

and ethnicity, but these are known to have poor

specificity, and indeed may not be independent (56).

Other candidates include biochemical markers of

inflammation which have been validated in prospec-

tive studies for markers such as C-reactive protein or

lipoprotein-associated phospholipase A2 (LpPLA2);

markers of endothelial dysfunction such as asymmet-

ric dimethylarginine, flow-mediated dilation or pulse

wave velocity and radiographical markers of athero-

sclerosis burden, including carotid intima media

thickness and coronary calcium scores (57). Which

test is best is yet unclear as they all vary in utility

depending on whether they identify prior disease or

can also be used to track response to treatment. If

these tests can be delivered at low unit cost, they could

be used to determine exclusion of lower risk individu-

als from life-long treatment. These extra tests may also

function to reassure patients who are concerned about

the implications of isolated high levels of single risk

factors, which are not caused by genetic dyslipidae-

mias or may identify for treatment those with aggres-

sive primary hypertension and those who require

treatment because of their specific additional risks.

Evidence base for vascular screening

However, the most crucial question is how accept-

able would this degree of screening for asymptomatic

disease be? Almost all the data on population screen-

ing relate to the emotive field of cancer. Vascular

programmes although effective in the long-term

(9,58) show a lower response rate to invitations with

an uptake of 47% to postal communications with

repeated reinforcement (59), and in other studies

29% for postal self-assessment (60). Some diabetes

studies show better recruitment by telephone (61).

The uptake of screening for established atheroscle-

rotic disease showed pronounced reductions in effi-

ciency for men, the elderly people and lower

socioeconomic classes – the highest risk groups (62).

Rates of adherence to follow-up visits at 1-year fall

to 50% (60) even before considering the pronounced

(similar) reductions in drug adherence for asymp-

tomatic conditions (63,64).

In addition, randomised clinical trials are rare in

this field and decision making seems to be driven by

health economics rather than evidence. The original

study in the field was the South East London Screen-

ing study of 7229 patients in 1967 of patients aged

40–64 years who were randomised to screening or

usual care (65). Initially, 20% refused cardiovascular

screening, and after 5 years there were no significant

differences in mortality or admissions between the

two groups. However, few effective lipid lowering or

antihypertensive interventions were available at the

time, so the results of this study may mimic the pre-

dominantly lifestyle effects seen in the Multiple Risk

Factor Intervention Trial (MRFIT) of 256,000

patients in the USA (8). The Stockport study

screened 8607 patients, three on occasions between

1989 and 1999, having initially screened 50,788 indi-

viduals at entry to the study (58). After 10 years,

smoking rates fell by 30% in high-risk patients, sys-

tolic blood pressure fell by 10 mmHg in high-risk

individuals (> 150 mmHg) compared with a

5 mmHg rise in lower risk, and cholesterol by 0.5–

0.7 mmol ⁄ l in high risk (> 6.5 mmol ⁄ l) compared

with a 0.2 mmol ⁄ l rise in lower risk individuals.

Unfortunately, no cardiovascular event data are

available for this study. More recently, the Sandwell

study randomised 11,901 patients in four primary

care practices compared with 8515 controls in two

practices to screening or opportunistic detection

(59). Although cardiovascular end-points are absent

from this study, cardiovascular risk estimation rates

doubled (61.9% vs. 27.9%) and so did rates of aspi-

rin (45.7% vs. 19.2%), antihypertensive (28.4% vs.

12.5%) and statin (49.0% vs. 21.6%) prescribing.

Data are awaited in whether cardiovascular event

benefits will follow from this intervention. Results

from the national familial hypercholesterolaemia

(FH) screening project in the Netherlands suggest

that it should be possible to identify the benefits of

risk screening on cardiovascular events, as FH

screening promotes improved treatment and has

demonstrated a 76% reduction in mortality with

linked screening and intervention approach (66).

Conclusions

Cardiovascular screening looks to be possible given

the existence of epidemiologically derived risk calcu-

lators and to have favourable health economics. Yet,

in practice, there may be considerable barriers to the

implementation of systematic screening, however,

useful in public health terms. There is an absence of

recent long-term clinical end-point as opposed to

surrogate marker ata, but the historical data are not

reassuring. There is a need for proper clinical trials

in this field.

Most cardiovascular disease occurs in patients at

low risk simply because the population with that

degree of risk is large which translates into a large

number of events overall even though the risk in any

individual is low. All a targeted risk approach can do

is to attempt to reduce the risk in the small popula-

tion at relatively high risk. Thus, only public health

interventions to promote healthier lifestyles, improve

diets, reduce smoking and reverse obesity will change

morbidity significantly overall, as this approach

How acceptable

would this

degree of

screening for

asymptomatic

disease be?

ª 2009 Blackwell Publishing Ltd Int J Clin Pract, July 2009, 63, 7, 989–996

994 Perspective

Page 7: Vascular risk screening: possible or too much, too soon?

reduces the risk factor burden by small amounts in

large numbers of people. Unfortunately, these

approaches are slow to take effect, are relatively

unglamorous and although the principles are well

known, the political temptation to a quick fix solu-

tion for cardiovascular disease through risk screening

with neglect of longer term approaches is very allur-

ing. Expensive unproven interventions should be

resisted until proper clinical trials are performed,

and policymakers need to remember that only

changes in public health will deliver the long-term

outcomes to lower risk individuals.

Disclosure

Dr Wierzbicki is a member of the South East Lon-

don Cardiac Network group on cardiovascular dis-

ease prevention.

A. S. Wierzbicki,1 T. M. Reynolds2

1Consultant in Metabolic Medicine andChemical Pathology,

St. Thomas’ Hospital,London SE1 7EH, UK

2Professor of Chemical Pathology,Queen’s Hospital, Belvedere Road,

Burton-on-Trent, Staffordshire DE13 0RB, UKEmail: [email protected]

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