Teodoro Marotta, Azienda Sanitaria Locale “Napoli 1”, Unità Operativa Assistenza Sanitaria di Base, Naples, Italy

A Risky Condition

Three new prospective, general-population-based studies published in the first months of this year [1-3], in which data of 24,800; 24,100; and 13,300 person-years, respectively, have been analyzed, highlight the link of metabolic syndrome (MS) with total [1,2] and cardiovascular [1-3] mortality. In the smallest of these studies [3], indeed, the association of cardiovascular mortality with MS was not stronger than that with the single components of the syndrome. However, just one year ago, in another wider population (46,300 person-years) an independent association between MS and cardiovascular mortality, beyond the effects of other well-established cardiovascular risk factors [4], was observed. Therefore, although the topic of the clinical relevance of MS is still debated [5,6], overall the last available data reinforce the conclusion of the recent meta-analysis by Gami et al. [7], i.e. that MS is a very risky condition. Analyzing data obtained from more than 170,000 persons, the authors found that the probability of cardiovascular events and death was increased by 78% in the presence of MS. The finding was statistically robust: 95% confidence interval (CI) of the relative risk was 1.58-2.00. When the usual cardiovascular risk factors were taken into account, the association was still highly significant (relative risk = 1.54, 95% CI = 1.32-1.79). Many recent studies have shown that incident cardiovascular disease is increased by MS [8-12], which is a predictor of cardiovascular events as good as the conventional coronary risk equations [13]. In a population-based study, the pooled risk of cardiovascular death, coronary heart disease, and stroke attributable to MS approximated that of low density lipoprotein (LDL) cholesterol [14].

A Condition to Which Some People Are More Susceptible Than Others

Women [7,15,16] and elderly people [9,17-20] appear particularly prone to the detrimental consequences of MS. Moreover, in old age the syndrome is more frequent [21,22] and is often underdiagnosed [23].

An association between low social status, as indicated by education, income, and work qualification, and MS prevalence has been observed in many countries, particularly in women [24-34]. This finding has been usually obtained across wide age ranges and very different social levels, or among active workers. However, it is present even in a low-level social context and among retired persons. In the 503 elderly, mostly retired, or never-employed outpatients (73% women) of the ICON study [35], attending two public clinics of the city of Naples, we have found that disparities in education level and in work qualification are associated with differences in blood pressure, body mass index, and serum lipid concentrations. Using the diagnostic criteria of the U.S. National Cholesterol and Education Program (ATP III) [36], odds ratio of MS in the highest of three education groups (just 8 years of school or more), as compared to the lowest one (not more than 4 years of school), was 0.28 (95% CI = 0.15-0.52). Odds ratio of MS in the highest of three work activity groups (craftsmen or more qualified jobs), with the lowest one as reference (mostly housewives), was 0.35 (95% CI = 0.20-0.62). Similar results were obtained using the International Diabetes Federation (IDF) diagnostic criteria [37]. Two separate multivariate logistic regressions where covariates were age, gender, and, alternatively, school education or work activity level, showed a highly significant association of MS with both these social indicators. Moreover, the least educated patients required a more intensive treatment than the others.

A Condition of Which Not Everybody Is Aware

Beside the increased prevalence of MS and, in general, the worse cardiovascular risk profile and clinical outcomes [28,38-41], people with a lower social position have often to face a worse medical assistance [42], which can increase the rate of missing diagnoses of cardiovascular risk factors and target organ damage. Elderly per se often implies social isolation and disadvantage and is frequently accompanied by reduced awareness and low compliance to treatment of cardiovascular disease [43-46]. In the ICON patients [35], we have made 462 new diagnoses, 156 of which concerning previously ignored cardiovascular risk factors (one every three patients) and 127 target organ diseases (one every four patients). Despite the fact that they were not spontaneously attending our clinics, but were referred by their general practitioners, 8% of hypertensives, 16% of diabetics, and 25% of dyslipidemics were not informed of their diseases. We cannot say if this incomplete awareness should be ascribed to an insufficient diagnostic workup or to communication problems, but the effect was that the impending risk for our patients was strongly increased. No wonder if none of them knew anything about MS; however, recent data indicate that even many doctors do not have adequate knowledge of the role of all its components as cardiovascular risk factors [47].

A Condition That Should Be Faced From a Double Perspective

The three points outlined above (high impact of MS on public health, high prevalence in the old age and in the disadvantaged social classes, scarce awareness of the problem among lay people and many health professionals) underscore the importance of health policies addressed to improve knowledge, prevention, diagnosis, and treatment of all MS components. Although extensive studies on cost-effectiveness of MS treatment in the general population are lacking, available data about several of its components indicate that improving their control would lead to economic advantages for the health systems and the whole society [48,49]. In particular, some neglected MS elements (abdominal obesity, low high density lipoprotein [HDL] cholesterol levels, hypertriglyceridemia, suboptimal blood pressure levels, impaired fasting glucose, impaired glucose tolerance) deserve more attention by public authorities, in addition to the effort often performed to face other cardiovascular risk factors, such as diabetes, frank hypertension, and high LDL cholesterol. Moreover, risk factor clustering should be addressed by health institutions as an additional target, at variance of what is done in some countries. The Italian National Drug Agency (Agenzia Italiana del Farmaco, AIFA), for example, states in its last official directory to family doctors that, in the case of multiple cardiovascular risk factors, the physician should choose which ones to treat and which ones to leave untreated, since “it cannot be proposed to assume drugs for each of them” [50]. Moreover, for the prescription of lipid-lowering drugs, AIFA refers physicians to the risk charts produced by the National Health Institute (Istituto Superiore di Sanità, ISS) [51], which take into account ages between 40 and 69 years, gender, smoking status, diabetes, systolic blood pressure, and total cholesterol. Unfortunately, they ignore older ages, visceral adiposity, triglyceride levels, and prediabetic states, as well as signs of target organ damage. HDL cholesterol, too, is omitted in the charts, although it can be entered in the risk calculator available on the ISS website.

But in approaching the treatment of MS, as always in medicine, there is another level to be considered, besides that of health policy and resource allocation ─ it is the level of interaction between the individual physician and the individual patient. To obtain adequate compliance is a critical step of each therapy. Moreover, cardiovascular disease prevention, and MS control in particular, are strictly linked to the patient’s lifestyle [52,53] and changes in this field often require strong motivation. Several authorities recommend addressing the issue of doctor-patient interaction to improve cardiovascular risk profile [36,54,55]. The Seventh Report of the U.S. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) discusses the role of patients’ trust in their doctor as a potent motivator to follow drug and lifestyle prescriptions [55]. Empathy is essential to build trusting and join the patient in a therapeutic alliance [55,56], which in turn can improve clinical outcomes. Systematic revisions of the literature strongly suggest that a good patient-physician relationship and a warm, reassuring style of communication significantly affects important outcomes, such as patient and physician satisfaction, perceived quality of life, anxiety, glycemic control, and blood pressure [57,58]. This is specially true for the elderly and the low social level patients, where compliance problems are more pronounced [41,46]. In the ICON study, providing an empathetic approach and implementing JNC 7 recommendations to build an effective therapeutic alliance has led to a significantly improved control rate of several cardiovascular risk factors, including obesity, hypertension, glucose intolerance, dyslipidemias, and smoking habit. The number of patients fitting the ATP III criteria for MS decreased from 47% of the whole sample at baseline to 34% at the end of follow-up [35] (p < 0.05 at the χ2 test).

The political and the individual-patient/individual-doctor levels are not independent, but on the contrary are strictly interconnected. On one hand, politicians have the responsibility to shape health systems where physicians are not bound by excessive regulatory ties, which can “sterilize” the patient-physician relationship and lead to the deprofessionalization of medicine [59]. On the other hand, each doctor, in his/her profession, is committed to hold and, if necessary, revitalize ethical values which are essential in building social trust towards the medical profession [60,61].

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Please address correspondence to:
Dr. Teodoro Marotta
Salita S. Antonio ai Monti 13
80135 Naples, Italy
E-mail: teodoro.marotta[at]libero.it