Editorial comment
Metabolic syndrome and cardiovascular risk
Síndrome metabólica e risco cardiovascular
Evangelista Rocha
Instituto de Medicina Preventiva e Saúde Pública – FMUL, Lisboa, Portugal
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The cluster of risk factors known as MetS is a major public health challenge, due to its high prevalence in the general population and its impact on the development of cardiovascular disease (CVD) and mortality.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">3</span></a> However, over the last three decades the debate about MetS has intensified, and some of its aspects are still generating a high degree of interest. The existence of different definitions of MetS hampered comparisons between studies and made it difficult to determine their value in clinical practice. Harmonization of the diagnostic criteria of MetS was not an easy process, but after a new worldwide definition was published in 2005,<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> medical societies with a particular interest in this condition reached a consensus and developed a unified definition, the Joint Interim Statement (JIS), in 2009.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">5</span></a> In this, a single cutoff value for waist circumference was abolished, to be replaced by ethnicity-specific national or regional cutoffs, and a platform was established to regulate the results of the investigation. Thus, the threshold for waist circumference is still not fixed.</p><p id="par0015" class="elsevierStylePara elsevierViewall">MetS affects about 25% of the population but its impact differs according to age and gender, which influence both its prevalence and its prognostic significance.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a> In the VALSIM study in Portugal, the prevalence of MetS (27.5% overall) increased with age in both sexes up to 80 years and was higher in women aged over 50 years.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a> The most prevalent components were increased blood pressure and abdominal obesity, as in the MORGAM Project<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a> and other studies. The prevalence of MetS clearly increases with age in both genders and is higher in women. Cross-sectional studies have been crucial to determining its prevalence; without them, neither the extent of the problem nor the population attributable risk could be determined, the latter depending on the relative risk (RR) or odds ratio of this clinical entity and on its prevalence.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">One question under discussion in the assessment of the cardiovascular risk of MetS is whether MetS is a cardiovascular risk factor beyond its individual components. The issue is important because if it is, MetS is a specific entity that must be taken into account in order to arrive at an accurate risk assessment. If the answer is no, treating individual MetS risk factors will be sufficient. In the literature there are studies which appear to show that MetS by itself has an effect and others in which the estimated effect was close to the null hypothesis using separate adjusted multivariate models. The presence of MetS is a good predictor of coronary heart disease (CHD) and stroke, although not as good as the Framingham Risk Score (FRS), and of type 2 diabetes, for which it is better than the FRS.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">9</span></a> In a systematic review and meta-analysis of longitudinal studies reporting associations between MetS and cardiovascular events or mortality, MetS had an RR of cardiovascular events and death of 1.78 (95% confidence interval 1.58-2.00). This association, which remained after adjustment for traditional cardiovascular risk factors, was stronger in women.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">10</span></a> However, this publication prompted a letter to the Editor<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a> with a different conclusion, based on an analysis of three reference studies. In the Atherosclerosis Risk In Communities (ARIC) study, McNeill et al.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">12</span></a> adjusted the risk associated with MetS for its components, reporting a hazard ratio (HR) of CHD of 0.91 for men and 0.71 for women, indicating that the risk of CHD associated with the syndrome was not in excess of the level explained by the presence of its individual components. In the West of Scotland Coronary Prevention Study (WOSCOPS), Sattar et al.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">13</span></a> stated that possession of MetS was not a significant predictor in the presence of the effects of its individual components when investigated in a multivariate model. Finally, Schillaci et al.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">14</span></a> reported an HR of 1.73, after adjustment for blood pressure as the only component of the MetS. In their reply, Gami et al. admitted that the available data were imperfect.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a> In a study based on 36 cohorts from the MORGAM Project with a 12.2-year follow-up, the CVD risk associated with MetS was higher in women than in men. Moreover, in men, the CVD risk was higher independently of age, whereas in women total CHD risk decreased significantly and the total stroke risk tended to increase (although not significantly) with older age. In women, MetS was associated with higher RR for CHD events that decreased with age, whereas RR for stroke tended to increase.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">6,15</span></a> A risk profile in which RR decreases with age while absolute risk increases means that the association between cause and possible effect is weak in older individuals. The same phenomenon is also seen with traditional risk factors, such as the relationship between smoking and CHD mortality,<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">16</span></a> or between hypertension and stroke.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">17</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In a comparison of the prognostic impact of different MetS definitions in predicting CVD, the JIS definition identified more patients with MetS, but all definitions showed higher HRs in females than in males.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">18</span></a> Using information from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort study of 6776 adults free of clinical CVD at baseline, latent class analysis showed a positive association between MetS and incident CHD events in both sexes.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">19</span></a> A systematic review and meta-analysis concluded that patients with MetS, but without diabetes, were still at high cardiovascular risk, with a two-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality, and that studies were needed to investigate whether the prognostic significance of MetS exceeds the risk associated with the sum of its individual components.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The link between type 2 diabetes and CVD has been recognized for many years. It is clear that individuals with diabetes have a greater likelihood of developing CVD than those without.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">20</span></a> Diabetes is an independent risk factor for CVD, even stronger in women, that by itself increases risk for a wide range of vascular diseases by about two-fold on average.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">21</span></a> However, the risk depends on the population and on the type of cardiovascular event (CHD, stroke or peripheral arterial disease).<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">21–23</span></a> Of the conditions predisposing to diabetes, MetS is one of the most prevalent. Indeed, the association between MetS and diabetes is a consequence of insulin resistance and strengthens as life-span and exposure increase. Hypertension, dyslipidemia and abdominal obesity commonly coexist with type 2 diabetes and further aggravate the risk, which is highest in people with type 2 diabetes and features of MetS.<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">23,24</span></a> Furthermore, diabetes confers excess mortality risk following acute coronary syndrome despite modern therapies, highlighting the poor prognosis of coronary patients with type 2 diabetes.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a> In order to prevent the development of risk factors for MetS, lifestyle changes are recommended, especially concerning diet and exercise.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">26</span></a> In the presence of MetS and diabetes, in addition to other measures that may help achieve, maintain or improve levels of risk parameters such as lipids, blood pressure and blood glucose, residual risk for CVD needs to be treated with appropriate drugs, as recommended in the guidelines. The apparent inconsistency in the association of triglycerides (TG) with CHD is not unexpected, given the complexities of TG metabolism.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">27</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Knowledge of the likely prognosis helps to decide on the most useful treatment,<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a> among other objectives (survival, case fatality, disease specific mortality, response, etc.). In this issue of the <span class="elsevierStyleItalic">Journal</span>, Timóteo et al.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a> monitored morbidity and mortality outcomes during follow-up in a cohort study of 300 individuals according to the presence or absence of MetS and CHD. Of note are the study's characterization of the occurrence of events under study in time using Cox regression analysis and its ability to handle censored data during a mean follow-up of 6.9 years with a low dropout rate (1.3%). Despite this, the study has some limitations, including its approach to dealing with adjusted analyses of the length of follow-up covariate and to testing potential interactions between independent variables and excluding multicollinearity. Important explanatory variables were omitted, such as major risk factors including the duration of exposure to type 2 diabetes. Type 2 diabetes and MetS are common in patients with CHD or stroke and their impact also depends on duration of exposure. Patients with diabetes and MetS are not at the same point in the course of their illness, since increased blood glucose is a late and possibly terminal manifestation of insulin resistance.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">5</span></a> Another limitation is that the sample was stratified into four groups, and consequently the number of some outcomes was low, so that not all differences between the groups reached statistical significance. Moreover, the plots of survival against time are shown in steps, but these steps would be smaller, and the figure would approximate a smooth curve, if the number of patients had been higher. The data do not confirm that MetS, an entity associated with increased cardiovascular risk in people without disease, is a marker of poor outcome in sick people (those with CHD in secondary prevention), but the limitations of the approach do not make this conclusion definitive.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Given the available evidence, it is unequivocal that MetS is associated with increased cardiovascular risk and even more with type 2 diabetes, an important health challenge in Europe and worldwide. It must therefore be prevented and identified early to control its components, the risk factors identified in the guidelines. Research on the risk of MetS in the area of prognosis, with the purpose of predicting the course of CVD (such as CHD) expressed as a probability that a particular event will occur in the future, faces methodological difficulties, and no more significant contributions to clinical practice are expected. However, with regard to the cardiovascular risk associated with dyslipidemia there is insufficient evidence, as a direct causal link between TG and CHD risk has still to be demonstrated. Hypertriglyceridemia should not be considered as a single entity but rather multiple conditions (elevated chylomicrons, an increase in the TG content of very low density lipoprotein (VLDL) particles or an increase in the total number of VLDL particles) that vary in their CHD risk, and so new research is needed to categorize phenotypes of hypertriglyceridemia.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0150" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of insulin resistance in human disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G. 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| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 13 | 9 | 22 |
| 2024 Outubro | 64 | 35 | 99 |
| 2024 Setembro | 56 | 22 | 78 |
| 2024 Agosto | 41 | 26 | 67 |
| 2024 Julho | 43 | 38 | 81 |
| 2024 Junho | 41 | 28 | 69 |
| 2024 Maio | 41 | 26 | 67 |
| 2024 Abril | 53 | 24 | 77 |
| 2024 Maro | 35 | 30 | 65 |
| 2024 Fevereiro | 35 | 20 | 55 |
| 2024 Janeiro | 31 | 26 | 57 |
| 2023 Dezembro | 27 | 25 | 52 |
| 2023 Novembro | 44 | 28 | 72 |
| 2023 Outubro | 21 | 20 | 41 |
| 2023 Setembro | 19 | 19 | 38 |
| 2023 Agosto | 31 | 27 | 58 |
| 2023 Julho | 14 | 13 | 27 |
| 2023 Junho | 35 | 10 | 45 |
| 2023 Maio | 59 | 29 | 88 |
| 2023 Abril | 27 | 8 | 35 |
| 2023 Maro | 80 | 24 | 104 |
| 2023 Fevereiro | 48 | 18 | 66 |
| 2023 Janeiro | 22 | 20 | 42 |
| 2022 Dezembro | 51 | 21 | 72 |
| 2022 Novembro | 49 | 36 | 85 |
| 2022 Outubro | 79 | 27 | 106 |
| 2022 Setembro | 31 | 40 | 71 |
| 2022 Agosto | 40 | 31 | 71 |
| 2022 Julho | 54 | 51 | 105 |
| 2022 Junho | 35 | 40 | 75 |
| 2022 Maio | 22 | 30 | 52 |
| 2022 Abril | 34 | 32 | 66 |
| 2022 Maro | 34 | 49 | 83 |
| 2022 Fevereiro | 29 | 27 | 56 |
| 2022 Janeiro | 27 | 25 | 52 |
| 2021 Dezembro | 25 | 33 | 58 |
| 2021 Novembro | 27 | 43 | 70 |
| 2021 Outubro | 47 | 43 | 90 |
| 2021 Setembro | 37 | 43 | 80 |
| 2021 Agosto | 28 | 43 | 71 |
| 2021 Julho | 30 | 44 | 74 |
| 2021 Junho | 34 | 28 | 62 |
| 2021 Maio | 49 | 38 | 87 |
| 2021 Abril | 65 | 63 | 128 |
| 2021 Maro | 63 | 21 | 84 |
| 2021 Fevereiro | 61 | 27 | 88 |
| 2021 Janeiro | 41 | 20 | 61 |
| 2020 Dezembro | 54 | 24 | 78 |
| 2020 Novembro | 50 | 22 | 72 |
| 2020 Outubro | 39 | 26 | 65 |
| 2020 Setembro | 50 | 20 | 70 |
| 2020 Agosto | 39 | 14 | 53 |
| 2020 Julho | 33 | 12 | 45 |
| 2020 Junho | 68 | 13 | 81 |
| 2020 Maio | 50 | 19 | 69 |
| 2020 Abril | 26 | 10 | 36 |
| 2020 Maro | 37 | 22 | 59 |
| 2020 Fevereiro | 108 | 54 | 162 |
| 2020 Janeiro | 23 | 11 | 34 |
| 2019 Dezembro | 64 | 19 | 83 |
| 2019 Novembro | 62 | 12 | 74 |
| 2019 Outubro | 67 | 12 | 79 |
| 2019 Setembro | 78 | 20 | 98 |
| 2019 Agosto | 26 | 26 | 52 |
| 2019 Julho | 80 | 66 | 146 |
| 2019 Junho | 36 | 33 | 69 |
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