also been a member of a Speakers Bureau for Forest

Laboratories, Inc, Novartis AG, and Pfizer Inc, and

served as consultant to Hoffman-La Roche, Inc and

Shinogi Pharma.

M. T. RosenbergMid Michigan Health Centers

Jackson, MichiganEmail: matttoren@yahoo.com

References1 Laumann EO, Palik A, Rosen RC. Sexual dysfunction in the United

States: prevalence and predictors. JAMA 1999; 281: 537–44.

2 Rosenberg MT, Sadovsky R. Identification and diagnosis of prema-

ture ejaculation. Int J Clin Pract 2007; 61: 903–8.

3 Hellstrom WJG. Update on treatment for premature ejaculation. Int

J Clin Pract 2011; 65: 16–26.

doi: 10.1111/j.1742-1241.2010.02512.x

ED ITORIAL

Cardiovascular screening: which populations, whatmeasures of risk?

Cardiovascular disease remains one of the greatest

causes of morbidity and mortality in developed

countries. It is the fastest increasing disease burden

in the developing world. Much epidemiological work

has defined the risk factors that account for 90% of

population attributable risk as being the old favour-

ites – age, gender, smoking, lipids, hypertension,

abdominal obesity, diabetes, lack of exercise, low

fruit and vegetable intake, alcohol intake and psy-

chosocial deprivation (1). Yet it is commonly

thought that these are mostly applicable only to the

miserable Northern world whilst in the Mediterra-

nean the sun shines, families frolic happily in the

street (to the songs of Zorba ⁄ Radio Tarifa or nowa-

days Abba) and the local diet obviates the need for

any further measures. The paper by Gomez-Huelgas

in this issue gives the lie to this rosy-tinted scenario

(2). The reality of life in a survey of 2270 partici-

pants is an obesity prevalence of 60%, sedentary life-

styles in 77%, 65% with dyslipidaemia, 27%

smoking, 33% with hypertension and 15% with dys-

glycaemia and 7% with diabetes. 30% have three

cardiovascular risk factors in the sample with an

average age of 45 years indicating a future high life-

time cardiovascular risk likely to merit drug treat-

ment. In fact the data are worse than those in a UK

self-selected cohort that underwent CVD risk screen-

ing in 2008 (3) and in the UK National Health

Survey for England (2006) (4) particularly with

regards to rates of smoking, obesity, hypertension

and diabetes. In fact the data from Andalusia shows

parallels with the USA where the highest burdens of

cardiometabolic risk are found in the sunniest

southern states (5). So why is the myth so prevalent?

In reality even the data on which the Mediterranean

diet ⁄ lifestyle is based was biased at the time. The

Seven Countries study deliberately recruited in rural

areas (6,7) and in the 40 years since lifestyles have

altered dramatically in parallel with rapid dysfunc-

tional development. Diets have changed, manual

work has disappeared but many ‘aspirational’ life-

style habits (e.g. smoking, calorie – dense foods)

remained unchanged. Fast carbohydrate –rich foods

are endemic and poverty allied with poor literacy

remain problems. In fact little differs in this regard

between North and South. Cardiovascular disease

and diabetes are diseases increasingly of poverty not

affluence (8). The problem for prevention pro-

grammes which are now increasingly being imple-

mented in national plans is how to access the

disease burden. The patients that attend for screen-

ing generally tend to be from the predominant

ethnic groups, female and wealthier (9). Systematic

screening is possible in universal health care systems

and the hope is that systematic screening will work

though historical evidence-based precedents are poor

(9). It is heartening that attendance rates for the

NHS programme in the UK are approaching 80%

but it will take many years before hard outcome

data can be gathered. More hopefully aggressive

public health campaigns such as draconian smoking

bans are showing clear health benefits (10). The

question remains though how to extend these to the

areas of nutrition in terms of reducing salt content,

saturated fats (and not just trans fats), carbohydrate

consumption and portion sizes. Slow progress is

Linked Comment: Jacobson. Int J Clin Pract 2011; 65: 82–101.

Linked Comment: Gomez-Huelgas et al. Int J Clin Pract 2011; 65: 35–40.

The highest

burdens of

cardiometa-

bolic risk are

found in the

sunniest

southern

states

Editorials 3

ª 2010 Blackwell Publishing Ltd Int J Clin Pract, January 2011, 65, 1, 1–5

being made but much more needs to happen before

future success is guaranteed.

One of the features of the anti-smoking campaign

was how it was possible to divide the scientific com-

munity against itself. A similar process is occurring

now in the debate about climate change. In cardio-

vascular medicine we commonly think of ourselves

as united in our aims and targets. Nothing could be

further from the truth when looked at in the eyes of

the sceptics- and these do exist and many cite the

standard ultra-libertarian arguments or decry the use

of drug therapies. The field of diabetes has just dug

itself a large hole by changing its diagnostic criteria

from glucose-based measures to HbA1c (11,12). The

arguments for changing are sensible and the evidence

base sound but the measure identifies a different

population to that found by fasting glucose measure-

ment let alone glucose tolerance tests. The data pro-

vided by an integrated measure of long-term

dysglycaemia naturally differs from a spot measure

and a (complex) physiological measure of glucose

load disposal. At low cut-offs associated with high

sensitivities comparative specificities are moderate

and non-concordant. Higher cut-offs increase speci-

ficity but lose sensitivity. This phenomenon can eas-

ily be reproduced with any modification to a

diagnostic algorithm (13).

In hyperlipidaemia we are in danger of making

the same mistake. In this issue Jacobson reviews the

extensive evidence based behind non-HDL choles-

terol (14). There is no doubt that this is a valid

measure of CVD risk with a large evidence base

and captures the increasing part of CVD risk associ-

ated with the metabolic syndrome, type 2 diabetes

and triglyceride-rich lipoproteins (15,16). It has

advantages over LDL-cholesterol in being more

accurate by having a simpler mathematical deriva-

tion- subtraction as opposed to the simple algebra

of the Friedrickson equation. Direct measures of

LDL-cholesterol may be more accurate in hypertri-

glyceridaemic patients but suffer from poor inter-

method concordance (17). Non-HDL also captures

most (but not all) of the risk inherent in the

endogenous apolipoprotein B -100 particle transport

system (18). So why is this development to be

questioned? Lipid management has evolved from an

initial focus on total cholesterol (1970s) to subfrac-

tions (HDL-C, LDL-C; 1990s) and lately some have

advocated a focus on subfractions of subfractions

(small dense HDL and LDL particles). Immense

effort has been invested in educating clinicians with

no particular interest in lipids in recognising the

prime characteristics of an abnormal profile. The

outcome of this of necessity has to be a simple

concept though many specialists have a tendency to

call them simplistic. The currently accepted version

includes total and LDL-cholesterol and is best

expressed in the form given by national guidelines

as targets for treatment on the basis that these mea-

sures capture pre-treatment risk and post-treatment

effects of evidence-based therapies (mostly statins).

The interest in non-HDL has risen in parallel with

the investigation of non-statin therapies for addi-

tional cardiovascular risk reduction. The role of

triglyceride-rich lipoproteins in increasing risk is

accepted but the evidence base for their treatment is

small. Monotherapy studies suggest benefits for both

fibrates (in some trials) (19) and niacin and meta-

analyses confirm the modest effects of these agents

(20–22). However trials of combination therapy on a

statin base are far rarer. Fibrates added to statins

gave little added benefit in the ACCORD study

though a sub-study analysis did suggest some

borderline additional benefit in patients with a high

atherogenic index (triglyceride: HDL ratio) (23). The

evidence for niacin in combination therapy is better

but comes from surrogate outcomes studies which

are open to criticism (24). The endpoint trials with

niacin in statin –treated patients are only now

underway.

So should we change measures? The change in car-

diometabolic risk and the ease of calculation of non-

HDL-C suggest it might be better than LDL-C. If the

niacin trials are positive then a unitary target that

captures the efficacy effects of both statins and

niacin ⁄ fibrates would be simpler. Virtually all the

new drugs in development are focused on the HDL

pathway and by extension benefit non-HDL-C

(25,26). The last statement actually gives the reason

to be wary- commercial interests are powerful chang-

ers of practice though the trials they perform and

the education they provide. Any new measure will

also have disadvantages. It is entirely possible that

the CETP inhibitor class that have dramatic effects

on lipid profiles and especially non-HDL-C will not

deliver the clinical benefits expected. Drugs that

improved lipid profiles but not CVD events are

known, if rather forgotten about – d-thyroxine,

oestrogen-based hormone replacement therapy.

Certainly we should debate new measures of risk but

until the evidence is available from trials such as

AIM-HIGH, HPS2-THRIVE and DALOUTCOMES

no changes should be made to current risk profiles.

We should also be very careful in our public

pronouncements on this issue as well as nothing falls

faster than a house divided against itself.

Disclosures

None.

4 Editorials

ª 2010 Blackwell Publishing Ltd Int J Clin Pract, January 2011, 65, 1, 1–5

A. S. WierzbickiConsultant in Metabolic Medicine ⁄ Chemical Pathology,

Guy’s & St Thomas’ Hospitals, Lambeth Palace Road,London SE1 7EH, T 0207 188 1256, F 0207 188 7325

Email: Anthony.Wierzbicki@kcl.ac.uk

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doi: 10.1111/j.1742-1241.2010.02566.x

Editorials 5

ª 2010 Blackwell Publishing Ltd Int J Clin Pract, January 2011, 65, 1, 1–5