Publications by authors named "Juan Pedro-Botet"

188 Publications

Cost-effectiveness evaluation of the use of PCSK9 inhibitors.

Endocrinol Diabetes Nutr 2021 Jun-Jul;68(6):369-371

Hospital Del Mar, Universitat Autònoma de Barcelona; Institut Hospital Del Mar D'Investigacions Mèdiques (IMIM), Barcelona, España.

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http://dx.doi.org/10.1016/j.endinu.2021.05.001DOI Listing
May 2021

Hydrophilic or Lipophilic Statins?

Front Cardiovasc Med 2021 20;8:687585. Epub 2021 May 20.

Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain.

Drugs can be classified as hydrophilic or lipophilic depending on their ability to dissolve in water or in lipid-containing media. The predominantly lipophilic statins (simvastatin, fluvastatin, pitavastatin, lovastatin and atorvastatin) can easily enter cells, whereas hydrophilic statins (rosuvastatin and pravastatin) present greater hepatoselectivity. Although the beneficial role of statins in primary and secondary cardiovascular prevention has been unequivocally confirmed, the possible superiority of one statin or other regarding their solubility profile is still not well-established. In this respect, although some previously published observational studies and clinical trials observed a superiority of lipophilic statins in cardiovascular outcomes, these results could also be explained by a greater low-density lipoprotein cholesterol reduction with this statin type. On the other hand, previous studies reported conflicting results as to the possible superiority of one statin type over the other regarding heart failure outcomes. Furthermore, adverse events with statin therapy may also be related to their solubility profile. Thus, the aim of the present review was to collect clinical evidence on possible differences in cardiovascular outcomes among statins when their solubility profile is considered, and how this may also be related to the occurrence of statin-related adverse effects.
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http://dx.doi.org/10.3389/fcvm.2021.687585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172607PMC
May 2021

Familial combined hyperlipidaemia/polygenic mixed hyperlipidaemia.

Clin Investig Arterioscler 2021 May;33 Suppl 2:43-49

Unidad de Lípidos, Servicio de Medicina Interna, H. U. Gregorio Marañón, Universidad Complutense, Madrid, España.

Familial combined hyperlipidaemia (FCH) is the most prevalent form of familial hyperlipidaemia with a multigenic origin and a complex pattern of inheritance. In this respect, FCH is an oligogenic primary lipid disorder due to interaction of genetic variants and mutations with environmental factors. Patients with FCH are at increased risk of cardiovascular disease and often have other associated metabolic conditions. Despite its relevance in cardiovascular prevention, FCH is frequently underdiagnosed and very often undertreated. In this review, emphasis is placed on the most recent advances in FCH, in order to increase its awareness and ultimately contribute to improving its clinical control.
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http://dx.doi.org/10.1016/j.arteri.2020.12.013DOI Listing
May 2021

Therapeutic targets in the treatment of dyslipidaemias: From statins to PCSK9 inhibitors. Unmet needs.

Clin Investig Arterioscler 2021 May;33 Suppl 1:46-52

Unidad de Lípidos y Riesgo Vascular, Servicio de Endocrinología y Nutrición, Hospital del Mar, Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, España.

The use of low-density lipoprotein cholesterol (LDLc)-lowering medications has led to a significant reduction of cardiovascular risk in both primary and secondary prevention. Statins represent the cornerstone of lipid-lowering treatment and substantially decreases cardiovascular morbidity and mortality. However, there are still unmet clinical needs in the management of dyslipidaemia. Indeed, it is difficult to achieve LDLc targets in many patients, particularly in those at high/very high cardiovascular risk and in those with very high baseline LDLc concentrations. Moreover, a considerable proportion of patients are unable to tolerate maximum statin doses, mostly due to muscle-related adverse effects. In the present narrative review, a summary is presented on the current knowledge on the effects of the different cholesterol-lowering drugs, including those recently approved by European and American regulatory agencies, on lipid profile, and on cardiovascular risk. Since difficult-to-treat patients may benefit from new combination therapies as a result of the emergence of new drugs with clinical evidence, updates of the clinical guidelines would be recommended.
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http://dx.doi.org/10.1016/j.arteri.2020.12.005DOI Listing
May 2021

Trends in Prevalence of Diabetes among Twin Pregnancies and Perinatal Outcomes in Catalonia between 2006 and 2015: The DIAGESTCAT Study.

J Clin Med 2021 Apr 30;10(9). Epub 2021 Apr 30.

Department of Endocrinology and Nutrition, Hospital del Mar, Passeig Marítim, 25-29, 08003 Barcelona, Spain.

The aims of our study were to evaluate the trends in the prevalence of diabetes among twin pregnancies in Catalonia, Spain between 2006 and 2015, to assess the influence of diabetes on perinatal outcomes of twin gestations and to ascertain the interaction between twin pregnancies and glycaemic status. A population-based study was conducted using the Spanish Minimum Basic Data Set. Cases of gestational diabetes mellitus (GDM) and pre-existing diabetes were identified using ICD-9-CM codes. Data from 743,762 singleton and 15,956 twin deliveries between 2006 and 2015 in Catalonia was analysed. Among twin pregnancies, 1088 (6.82%) were diagnosed with GDM and 83 (0.52%) had pre-existing diabetes. The prevalence of GDM among twin pregnancies increased from 6.01% in 2006 to 8.48% in 2015 ( < 0.001) and the prevalence of pre-existing diabetes remained stable (from 0.46% to 0.27%, = 0.416). The risk of pre-eclampsia was higher in pre-existing diabetes (15.66%, = 0.015) and GDM (11.39%, < 0.001) than in normoglycaemic twin pregnancies (7.55%). Pre-existing diabetes increased the risk of prematurity (69.62% vs. 51.84%, = 0.002) and large-for-gestational-age (LGA) infants (20.9% vs. 11.6%, = 0.001) in twin gestations. An attenuating effect on several adverse perinatal outcomes was found between twin pregnancies and the presence of GDM and pre-existing diabetes. As a result, unlike in singleton pregnancies, diabetes did not increase the risk of all perinatal outcomes in twins and the effect of pre-existing diabetes on pre-eclampsia and LGA appeared to be attenuated. In conclusion, prevalence of GDM among twin pregnancies increased over the study period. Diabetes was associated with a higher risk of pre-eclampsia, prematurity and LGA in twin gestations. However, the impact of both, pre-existing diabetes and GDM, on twin pregnancy outcomes was attenuated when compared with its impact on singleton gestations.
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http://dx.doi.org/10.3390/jcm10091937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125732PMC
April 2021

Low HDL and high triglycerides predict COVID-19 severity.

Sci Rep 2021 03 30;11(1):7217. Epub 2021 Mar 30.

Lipid Unit, University Hospital del Mar, Barcelona Autonomous University, Barcelona, Spain.

Lipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain the association of the plasma lipid profile with SARS-CoV-2 infection clinical evolution. Observational cross-sectional study including 1411 hospitalized patients with COVID-19 and an available standard lipid profile prior (n: 1305) or during hospitalization (n: 297). The usefulness of serum total, LDL, non-HDL and HDL cholesterol to predict the COVID-19 prognosis (severe vs mild) was analysed. Patients with severe COVID-19 evolution had lower HDL cholesterol and higher triglyceride levels before the infection. The lipid profile measured during hospitalization also showed that a severe outcome was associated with lower HDL cholesterol levels and higher triglycerides. HDL cholesterol and triglyceride concentrations were correlated with ferritin and D-dimer levels but not with CRP levels. The presence of atherogenic dyslipidaemia during the infection was strongly and independently associated with a worse COVID-19 infection prognosis. The low HDL cholesterol and high triglyceride concentrations measured before or during hospitalization are strong predictors of a severe course of the disease. The lipid profile should be considered as a sensitive marker of inflammation and should be measured in patients with COVID-19.
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http://dx.doi.org/10.1038/s41598-021-86747-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010012PMC
March 2021

Impact of statin therapy on LDL and non-HDL cholesterol levels in subjects with heterozygous familial hypercholesterolaemia.

Nutr Metab Cardiovasc Dis 2021 05 28;31(5):1594-1603. Epub 2021 Jan 28.

Endocrinology and Nutrition Department. Hospital Del Mar; Paseo Marítimo, 25-29; E-08003, Barcelona, Spain; Department of Medicine, Universitat Autònoma de Barcelona. Campus Universitari Mar; Dr. Aiguader, 80; E-08003, Barcelona, Spain; Institut Hospital Del Mar D'Investigacions Mèdiques (IMIM), Dr. Aiguader, 80; E-08003, Barcelona, Spain. Electronic address:

Background And Aims: Cardiovascular risk in heterozygous familial hypercholesterolaemia (HeFH) is driven by LDL cholesterol levels. Since lipid response to statin therapy presents individual variation, this study aimed to compare mean LDL and non-HDL cholesterol reductions and their variability achieved with different types and doses of the most frequently prescribed statins.

Methods And Results: Among primary hypercholesterolaemia cases on the Spanish Arteriosclerosis Society registry, 2894 with probable/definite HeFH and complete information on drug therapy and lipid profile were included. LDL cholesterol reduction ranged from 30.2 ± 17.0% with simvastatin 10 mg to 48.2 ± 14.7% with rosuvastatin 40 mg. After the addition of ezetimibe, an additional 26, 24, 21 and 24% reduction in LDL cholesterol levels was obtained for rosuvastatin, 5, 10, 20 and 40 mg, respectively. Subjects with definite HeFH and a confirmed genetic mutation had a more discrete LDL cholesterol reduction compared to definite HeFH subjects with no genetic mutation. A suboptimal response (<15% or <30% reduction in LDL cholesterol levels, respectively with low-/moderate-intensity and high-intensity statin therapy) was observed in 13.5% and, respectively, 20.3% of the subjects.

Conclusion: According to the LDL cholesterol reduction in HeFH patients, the ranking for more to less potent statins was rosuvastatin, atorvastatin and simvastatin; however, at maximum dosage, atorvastatin and rosuvastatin were nearly equivalent. HeFH subjects with positive genetic diagnosis had a lower lipid-lowering response. Approximately 1 in 5 patients on high-intensity statin therapy presented a suboptimal response.
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http://dx.doi.org/10.1016/j.numecd.2021.01.014DOI Listing
May 2021

LDL Cholesterol Reduction Variability with Different Types and Doses of Statins in Monotherapy or Combined with Ezetimibe. Results from the Spanish Arteriosclerosis Society Dyslipidaemia Registry.

Cardiovasc Drugs Ther 2021 Feb 8. Epub 2021 Feb 8.

Endocrinology and Nutrition Department, Hospital Universitario del Mar, Paseo Marítimo, 25-29, E-08003, Barcelona, Spain.

Purpose: Low-density lipoprotein (LDL) cholesterol reduction by statin therapy is dose-dependent, varies among different statins, and has wide inter-individual variability. The present study aimed to compare mean LDL cholesterol reduction and its variability achieved with different doses of the three statins most frequently used in monotherapy or combined with ezetimibe in a real clinical setting.

Methods: Of 5620 cases with primary hypercholesterolemia on the Spanish Arteriosclerosis Society Registry, 1004 with non-familial hypercholesterolemia and complete information on drug therapy and lipid profile were included.

Results: The lowest mean percentage LDL cholesterol reduction was observed with simvastatin 10 mg (32.5 ± 18.5%), while the highest mean percentage LDL reduction was obtained with rosuvastatin 40 mg (58.7 ± 18.8%). As to combined treatment, the lowest and highest mean percentage LDL cholesterol reductions were obtained with simvastatin 10 mg combined with ezetimibe (50.6 ± 24.6%) and rosuvastatin 40 mg combined with ezetimibe (71.6 ± 11.1%), respectively. Factors associated with a suboptimal response were male sex, lower age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol reduction (OR 0.603, p < 0.001).

Conclusion: In a real clinical setting, rosuvastatin was superior to the other statins in lowering LDL cholesterol, both as monotherapy or combined with ezetimibe. Factors associated with a suboptimal response in LDL cholesterol decline were male sex, age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol improvement.
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http://dx.doi.org/10.1007/s10557-020-07137-zDOI Listing
February 2021

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Cardiovascular Prevention Guidelines.

Clin Investig Arterioscler 2021 Mar-Apr;33(2):85-107. Epub 2021 Jan 22.

Instituto de Salud Carlos III, Madrid, España.

We present the adaptation for Spain of the updated European Cardiovascular Prevention Guidelines. In this update, greater stress is laid on the population approach, and especially on the promotion of physical activity and healthy diet through dietary, leisure and active transport policies in Spain. To estimate vascular risk, note should be made of the importance of recalibrating the tables used, by adapting them to population shifts in the prevalence of risk factors and incidence of vascular diseases, with particular attention to the role of chronic kidney disease. At an individual level, the key element is personalised support for changes in behaviour, adherence to medication in high-risk individuals and patients with vascular disease, the fostering of physical activity, and cessation of smoking habit. Furthermore, recent clinical trials with PCSK9 inhibitors are reviewed, along with the need to simplify pharmacological treatment of arterial hypertension to improve control and adherence to treatment. In the case of patients with type 2 diabetes mellitus and vascular disease or high vascular disease risk, when lifestyle changes and metformin are inadequate, the use of drugs with proven vascular benefit should be prioritised. Lastly, guidelines on peripheral arterial disease and other specific diseases are included, as is a recommendation against prescribing antiaggregants in primary prevention.
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http://dx.doi.org/10.1016/j.arteri.2020.11.004DOI Listing
January 2021

Atherogenic dyslipemia: the other pandemic, associated with diabesity.

Clin Investig Arterioscler 2021 Jan-Feb;33(1):30-32

Grupo de trabajo de Dislipemia Aterogénica. Sociedad Española de Arteriosclerosis; Unidad de Lípidos y Riesgo Vascular. Hospital del Mar. Barcelona.

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http://dx.doi.org/10.1016/j.arteri.2020.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833629PMC
January 2021

Ethnic differences in the impact of gestational diabetes on macrosomia.

Minerva Endocrinol 2021 Jan 12. Epub 2021 Jan 12.

Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain.

Background: Previous studies reported an ethnic disparity in gestational diabetes mellitus-associated birth outcomes, with some suggesting that macrosomia increases to a lesser extent in groups at high risk, the opposite of the pattern observed by others. Our aim was to evaluate ethnic variation in the impact of gestational diabetes mellitus (GDM).

Methods: A case-control study evaluating pregnancy outcomes was conducted in women with and without GDM from 5 ethnic groups. Data on GDM were collected between January 2004 and July 2017. Women giving birth between May 2013 and July 2017 in whom pre-existing diabetes had been ruled out served as controls. A multivariate logistic regression analysis was performed to determine factors independently associated with macrosomia.

Results: 852 GDM women and 3,803 controls were included. In Caucasian and East-Asian women excessive gestational weight gain (OR 2.273, 95% CI 1.364-3.788 and OR 3.776, 95% CI 0.958-14.886) was an independent predictor of macrosomia. In Latin-American and Moroccan women, obesity (OR 1.774, 95% CI 1.219-2.581 and OR 1.656, 95% CI 1.054-2.601), GDM (OR 2.440; 95% CI 1.048-5.679 and OR 3.249, 95% CI 1.269-8.321) and gestational weight gain but only for Latin-American women (OR 2.365, 95% CI 1.039-5.384) were associated with macrosomia. In South-Central Asian women, only GDM was associated with macrosomia (OR 3.701, 95% CI 1.437-9.532).

Conclusions: GDM is an independent predictor of macrosomia in Latin-American, South-Central Asian and Moroccan women but not in Caucasian or East-Asian women in whom other factors play a more important role.
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http://dx.doi.org/10.23736/S0391-1977.20.03301-5DOI Listing
January 2021

EFFECT oF STATIN THERAPY oN SARS-CoV-2 INFECTION-RELATED.

Eur Heart J Cardiovasc Pharmacother 2020 Nov 2. Epub 2020 Nov 2.

Lipid Unit, University Hospital del Mar, Barcelona Autonomous University, Barcelona, Spain.

Aim: Assessing the effect of statin therapy at hospital admission for COVID-19 on in-hospital mortality.

Methods And Results: Retrospective observational study. Patients taking statins were 11 years older and had significantly more comorbidities than patients who were not taking statins. A genetic matching (GM) procedure was performed prior to analysis of the mortality risk. A Cox proportional hazards model was used for the cause-specific hazard (CSH) function, and a competing-risks Fine and Gray (FG) model was also used to study the direct effects of statins on risk.Data from reverse transcription-polymerase chain reaction-confirmed 2157 SARS-CoV-2-infected patients (1234 men, 923 women; age: 67 y/o (IQR 54-78)) admitted to the hospital were retrieved from the clinical records in anonymized manner. 353 deaths occurred. 581 patients were taking statins. Univariate test after GM showed a significantly lower mortality rate in patients on statin therapy than the matched non-statin group (19.8% vs. 25.4%, χ2 with Yates continuity correction: p = 0.027). The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared to the GM non-statin group (17.4%; p = 0.045). The Cox model applied to the CSH function (HR = 0.58(CI: 0.39-0.89); p = 0.01) and the competing risks FG model (HR = 0.60(CI: 0.39-0.92); p = 0.02) suggest that statins are associated with reduced COVID-19-related mortality.

Conclusions: A lower SARS-CoV-2 infection-related mortality was observed in patients treated with statin therapy prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.
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http://dx.doi.org/10.1093/ehjcvp/pvaa128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665420PMC
November 2020

Trends in prevalence of pre-existing diabetes and perinatal outcomes: a large, population-based study in Catalonia, Spain, 2006-2015.

BMJ Open Diabetes Res Care 2020 10;8(1)

Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain.

Introduction: This study aims to assess trends in the prevalence of pre-existing diabetes and whether the risk of adverse perinatal outcomes decreased in women between 2006 and 2015 in Catalonia, Spain.

Research Design And Methods: A population-based study of 743 762 singleton deliveries between 2006 and 2015 in Catalonia, Spain, was conducted using data from the Spanish Minimum Basic Data Set. Cases of type 1 diabetes (T1DM) and 'type 2 diabetes and other pre-existing diabetes' ('T2DM and other PGD') were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Crude and age-adjusted annual prevalences were calculated. Poisson regression model was used to assess trends in prevalence and perinatal outcomes during the study period.

Results: Overall prevalences of pre-existing diabetes, T1DM and 'T2DM and other PGD' were 0.52% (95% CI 0.51 to 0.54), 0.17% (95% CI 0.17 to 0.18) and 0.35% (95% CI 0.33 to 0.36), respectively. From 2006 to 2015, rates increased for pre-existing diabetes (from 0.43 (95% CI 0.39 to 0.48) to 0.56% (0.50 to 0.62), p<0.001), T1DM (from 0.14 (0.11 to 0.17) to 0.20% (0.17 to 0.23), p<0.001) and 'T2DM and other PGD' (from 0.29 (0.25 to 0.33) to 0.36% (0.31 to 0.40), p<0.001). Pre-eclampsia rose in women with pre-existing diabetes (from 4.38% to 8.97%, adjusted p<0.001), T1DM (from 3.85% to 12.88%, p=0.005) and 'T2DM and other PGD' (from 4.63% to 6.78%, adjusted p=0.01). Prevalence of prematurity, cesarean section and small for gestational age remained stable in all diabetes groups. However, the prevalence of macrosomia fell in women with pre-existing diabetes (from 18.18% to 11.9%, adjusted p=0.011) and 'T2DM and other PGD' (from 14.71% to 11.06%, non-adjusted p=0.022, adjusted p=0.305) and large for gestational age decreased in all diabetes groups (from 39.73% to 30.25% in pre-existing diabetes, adjusted p=0.004).

Conclusions: The prevalence of pre-existing diabetes increased significantly in Catalonia between 2006 and 2015. Despite improvements in outcomes related to excessive birth weight, pre-eclampsia rates are rising and overall perinatal outcomes in women with pre-existing diabetes continue to be markedly worse than in the population without diabetes.
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http://dx.doi.org/10.1136/bmjdrc-2020-001254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592254PMC
October 2020

[Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Cardiovascular Prevention Guidelines].

Hipertens Riesgo Vasc 2021 Jan-Mar;38(1):21-43. Epub 2020 Oct 14.

Instituto de Salud Carlos III, Madrid, España.

We present the adaptation for Spain of the updated European Cardiovascular Prevention Guidelines. In this update, greater stress is laid on the population approach, and especially on the promotion of physical activity and healthy diet through dietary, leisure and active transport policies in Spain. To estimate vascular risk, note should be made of the importance of recalibrating the tables used, by adapting them to population shifts in the prevalence of risk factors and incidence of vascular diseases, with particular attention to the role of chronic kidney disease. At an individual level, the key element is personalised support for changes in behaviour, adherence to medication in high-risk individuals and patients with vascular disease, the fostering of physical activity, and cessation of smoking habit. Furthermore, recent clinical trials with PCSK9 inhibitors are reviewed, along with the need to simplify pharmacological treatment of arterial hypertension to improve control and adherence to treatment. In the case of patients with type 2 diabetes mellitus and vascular disease or high vascular disease risk, when lifestyle changes and metformin are inadequate, the use of drugs with proven vascular benefit should be prioritised. Lastly, guidelines on peripheral arterial disease and other specific diseases are included, as is a recommendation against prescribing antiaggregants in primary prevention.
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http://dx.doi.org/10.1016/j.hipert.2020.07.004DOI Listing
October 2020

Additional Metabolic Effects of Bariatric Surgery in Patients with a Poor Mid-Term Weight Loss Response: A 5-Year Follow-Up Study.

J Clin Med 2020 Oct 1;9(10). Epub 2020 Oct 1.

Departament de Medicina, Universitat Autònoma de Barcelona, 08139 Barcelona, Spain.

To ascertain the 5-year metabolic effects of bariatric surgery in poor weight loss (WL) responders and establish associated factors.

Methods: Retrospective analysis of a non-randomised prospective cohort of bariatric surgery patients completing a 5-year follow-up. Mid-term poor WL was considered when 5-year excess weight loss was <50%.

Results: Forty-three (20.3%) of the 212 included patients were mid-term poor WL responders. They showed an improvement in all metabolic markers at 2 years, except for total cholesterol. This improvement with respect to baseline was maintained at 5 years for plasma glucose, HbA1c, HOMA, HDL and diastolic blood pressure; however, LDL cholesterol, triglycerides and systolic blood pressure were similar to presurgical values. Comorbidity remission rates were comparable to those obtained in the good WL group except for hypercholesterolaemia (45.8% vs. poor WL, = 0.005). On multivariate analysis, lower baseline HDL cholesterol levels, advanced age and lower preoperative weight loss were independently associated with poor mid-term WL.

Conclusions: Although that 1 in 5 patients presented suboptimal WL 5 years after bariatric surgery, other important metabolic benefits were maintained.
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http://dx.doi.org/10.3390/jcm9103193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600546PMC
October 2020

[Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Cardiovascular Prevention Guidelines.]

Rev Esp Salud Publica 2020 Sep 11;94. Epub 2020 Sep 11.

Instituto de Salud Carlos III. Madrid. España.

We present the adaptation for Spain of the updated European Cardiovascular Prevention Guidelines. In this update, greater stress is laid on the population approach, and especially on the promotion of physical activity and healthy diet through dietary, leisure and active transport policies in Spain. To estimate vascular risk, note should be made of the importance of recalibrating the tables used, by adapting them to population shifts in the prevalence of risk factors and incidence of vascular diseases, with particular attention to the role of chronic kidney disease. At an individual level, the key element is personalised support for changes in behaviour, adherence to medication in high-risk individuals and patients with vascular disease, the fostering of physical activity, and cessation of smoking habit. Furthermore, recent clinical trials with PCSK9 inhibitors are reviewed, along with the need to simplify pharmacological treatment of arterial hypertension to improve control and adherence to treatment. In the case of patients with type 2 diabetes mellitus and vascular disease or high vascular disease risk, when lifestyle changes and metformin are inadequate, the use of drugs with proven vascular benefit should be prioritised. Lastly, guidelines on peripheral arterial disease and other specific diseases are included, as is a recommendation against prescribing antiaggregants in primary prevention.
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September 2020

Bariatric surgery and LDL cholesterol (BASALTO) trial study protocol: randomised controlled study evaluating the effect of gastric bypass versus sleeve gastrectomy on high LDL cholesterol.

BMJ Open 2020 09 10;10(9):e037712. Epub 2020 Sep 10.

Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain.

Introduction: Observational studies have shown gastric bypass to be superior to sleeve gastrectomy in terms of low-density lipoprotein (LDL) cholesterol improvement. If these results are confirmed in randomised controlled trials, presurgical LDL cholesterol status could be a relevant factor in surgical procedure election. Furthermore, it is also necessary to establish the mechanisms by which LDL cholesterol improves after surgery and whether qualitative and quantitative changes occur in the different lipoprotein subclasses. The first objective is to ascertain whether high LDL cholesterol levels before surgery can be considered an additional factor when selecting the most appropriate surgical procedure for each patient (gastric bypass or sleeve gastrectomy). Hence, the 1-year remission rates of high LDL cholesterol after gastric bypass and sleeve gastrectomy in patients with morbid obesity will be compared. Secondary objectives were (1) to compare changes in other lipoproteins and LDL composition and (2) to study the pathophysiologic mechanisms related to LDL cholesterol remission.

Methods And Analysis: A randomised clinical trial, with intention-to-treat analysis, will be conducted to compare LDL cholesterol remission between gastric bypass and sleeve gastrectomy, with a 12-month follow-up. Inclusion criteria will be patients between 18 and 60 years of age with body mass index ≥40 kg/m or ≥35 kg/m with significant obesity-related comorbidity and high LDL cholesterol levels. Patients will be evaluated preoperatively and at 3, 6 and 12 months after bariatric surgery. Examinations will include routine blood chemistry, anthropometric measurements, food intake recall, physical activity questionnaires and serum samples for lipidomic and lipoprotein characterisation.

Ethics And Dissemination: Ethics approval has been granted by the Parc de Salut Mar Ethics Committee (2019/8471/I). The study and its conclusions regarding the primary and secondary objectives will be presented as manuscripts submitted for peer-reviewed journal publication.

Trial Registration Number: NCT03975478.
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http://dx.doi.org/10.1136/bmjopen-2020-037712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485237PMC
September 2020

The Forgotten Gastrointestinal Tract in COVID-19 Infection.

Clin Transl Gastroenterol 2020 07;11(7):e00216

Hospital del Mar, Barcelona, Spain.

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http://dx.doi.org/10.14309/ctg.0000000000000216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386333PMC
July 2020

The Roses Ocean and Human Health Chair: A New Way to Engage the Public in Oceans and Human Health Challenges.

Int J Environ Res Public Health 2020 07 14;17(14). Epub 2020 Jul 14.

European Centre for Environment and Human Health, University of Exeter Medical School, Cornwall TR1 3HD, UK.

Involving and engaging stakeholders is crucial for studying and managing the complex interactions between marine ecosystems and human health and wellbeing. The Oceans and Human Health Chair was founded in the town of Roses (Catalonia, Spain, NW Mediterranean) in 2018, the fruit of a regional partnership between various stakeholders, and for the purpose of leading the way to better health and wellbeing through ocean research and conservation. The Chair is located in an area of the Mediterranean with a notable fishing, tourist, and seafaring tradition and is close to a marine reserve, providing the opportunity to observe diverse environmental conditions and coastal and maritime activities. The Chair is a case study demonstrating that local, collaborative, transdisciplinary, trans-sector, and bottom-up approaches offer tremendous opportunities for engaging coastal communities to help support long-lasting solutions that benefit everyone, and especially those living by the sea or making their living from the goods and services provided by the sea. Furthermore, the Chair has successfully integrated most of its experts in oceans and human health from the most prestigious institutions in Catalonia. The Chair focuses on three main topics identified by local stakeholders: Fish and Health; Leisure, Health, and Wellbeing; and Medicines from the Sea. Led by stakeholder engagement, the Chair can serve as a novel approach within the oceans and human health field of study to tackle a variety of environmental and public health challenges related to both communicable and non-communicable diseases, within the context of sociocultural issues. Drawing on the example provided by the Chair, four principles are established to encourage improved participatory processes in the oceans and human health field: bottom-up, "think local", transdisciplinary and trans-sectorial, and "balance the many voices".
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http://dx.doi.org/10.3390/ijerph17145078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400534PMC
July 2020

Atherosclerosis and inflammation. New therapeutic approaches.

Med Clin (Barc) 2020 09 20;155(6):256-262. Epub 2020 Jun 20.

Unidad de Lípidos y Riesgo Vascular, Servicio de Endocrinología y Nutrición, Hospital del Mar, Universidad Autónoma de Barcelona, Barcelona, España.

The recognition of atherogenesis as an active process rather than a passive cholesterol storage disease has underlined key inflammatory mechanisms. Hence, innate and adaptive immune responses play an important role in the onset and progression of atherosclerosis. More recently, some clinical studies were designed to address the impact of anti-inflammatory intervention strategies in reducing risk of cardiovascular disease beyond the management of classic risk factors. Therefore, we review first the pathophysiological contribution of inflammation to atherosclerosis and the effect of lipid-lowering drugs on inflammatory biomarkers. Next, we address the effect of classic anti-inflammatory drugs, pharmacological therapies targeting specific inflammatory mediators and vaccines in cardiovascular prevention.
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http://dx.doi.org/10.1016/j.medcli.2020.04.024DOI Listing
September 2020

Atherogenic Dyslipidaemia 2019. Consensus document of the Atherogenic Dyslipidaemia Group of the Spanish Arteriosclerosis Society.

Clin Investig Arterioscler 2020 May - Jun;32(3):120-125. Epub 2020 Apr 11.

Servicio de Medicina Interna, Hospital de Bellvitge, CIBERobn, Fipec; Universidad de Barcelona; IBIDELL, Barcelona, España.

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http://dx.doi.org/10.1016/j.arteri.2019.11.004DOI Listing
June 2021

LDL cholesterol in one step.

Med Clin (Barc) 2020 10 7;155(7):316-317. Epub 2020 Mar 7.

Servicio de Endocrinología y Nutrición, Hospital del Mar, Barcelona, España; Departament de Medicina, Universitat Autònoma de Barcelona, Campus Universitari Mar, Barcelona, España.

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http://dx.doi.org/10.1016/j.medcli.2019.12.009DOI Listing
October 2020

Triglycerides, HDL cholesterol and atherogenic dyslipidaemia in the 2019 European guidelines for the management of dyslipidaemias.

Clin Investig Arterioscler 2020 Sep - Oct;32(5):209-218. Epub 2020 Feb 6.

Unidad de Lípidos, Servicio de Medicina Interna, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, España.

In general, both European and American clinical guidelines have addressed the management of atherogenic dyslipidaemia in an unconvincing and even superficial way, largely because of the available therapeutic limitations. Consequently, this type of dyslipidaemia is underdiagnosed, under-treated, and under-controlled. Given the recent presentation of the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology on the management of dyslipidaemias, it seems appropriate to examine its position with respect to atherogenic dyslipidaemia and/or its main components, the increase in triglyceride-rich lipoproteins, and the decrease of high-density lipoprotein cholesterol.
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http://dx.doi.org/10.1016/j.arteri.2019.12.003DOI Listing
February 2020

Lipid-lowering treatment in secondary prevention of ischaemic cerebrovascular disease.

Clin Investig Arterioscler 2020 Jul - Aug;32(4):175-182. Epub 2020 Feb 5.

Servicio de Endocrinología y Nutrición, Hospital del Mar, Barcelona, España; Departament de Medicina, Universitat Autònoma de Barcelona, Campus Universitari Mar, Barcelona, España; Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, España. Electronic address:

Stroke is the second cause of death after myocardial infarction, and the main cause of acquired disability. Patients with ischaemic stroke have a higher risk of future vascular events, including recurrent stroke, myocardial infarction, and death by vascular cause. The initial epidemiological studies demonstrated a weak or non-existent relationship between cholesterolaemia and stroke. Subsequently, statin intervention trials showed a reduction in the risk of recurrence of cerebrovascular events. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL), the first clinical trial designed to assess effects of statin therapy in secondary stroke prevention, highlighted the reduction of stroke recurrence with atorvastatin 80mg/daily in patients with a recent ischaemic established or transient stroke, with a modest increase in the rate of haemorrhagic stroke. Successive studies have also reported the benefits of statin therapy combined with ezetimibe or PCSK9 inhibitors in primary and secondary ischaemic stroke prevention. Since 80% of recurrent cerebrovascular events could be prevented, it is considered of interest to carry out a narrative review of the benefits of lipid-lowering therapy in the secondary prevention of ischaemic cerebrovascular disease.
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http://dx.doi.org/10.1016/j.arteri.2019.12.002DOI Listing
July 2021

Morbid obesity and dyslipidaemia: The impact of bariatric surgery.

Clin Investig Arterioscler 2020 Mar - Apr;32(2):79-86. Epub 2020 Jan 20.

Servicio de Endocrinología y Nutrición, Hospital del Mar, Barcelona, España; Departamento de Medicina, Universitat Autònoma de Barcelona, Campus Universitari Mar, Barcelona, España; Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, España. Electronic address:

Obesity prevalence has presented an exponential increase in the last decades, becoming a first order public health issue. Dyslipidemia of obesity, characterized by low levels of high density lipoprotein (HDL) cholesterol, hypertriglyceridemia and small and dense low-density lipoprotein (LDL) particles, is partly responsible for the high residual cardiovascular risk of this clinical situation. On the other hand, bariatric surgery (BS) is the most effective treatment for obesity, obtaining a greater weight loss than achieved with conventional medical therapy and favoring the improvement or remission of associated comorbidities. The most commonly used BS techniques nowadays are laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG). Both of these procedures have obtained similar results in terms of weight loss and comorbidity remission such as type2 diabetes mellitus or hypertension. A differential feature between both techniques could be the different impact on the lipoprotein profile. In this respect, previous studies with short and mid-term follow-up have proved LRYGB to be superior to LSG in total and LDL cholesterol reduction. Results regarding triglycerides and HDL cholesterol are contradictory. Therefore, we consider of interest to review the effects of BS at short and mid-term follow-up on lipoprotein profile, as well as the remission rates of the different lipid abnormalities and the possible related factors.
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http://dx.doi.org/10.1016/j.arteri.2019.11.001DOI Listing
December 2020

Behavioural cardiovascular risk factors and prevalence of diabetes in subjects with familial hypercholesterolaemia.

Eur J Prev Cardiol 2020 10 8;27(15):1649-1660. Epub 2020 Jan 8.

Lipid Unit, Hospital Universitario Miguel Servet, IIS Aragon, CIBERCV, Zaragoza, Spain.

A low prevalence of type 2 diabetes mellitus has been reported in familial hypercholesterolaemia. Whether a healthier lifestyle could explain it has not been explored. This cross-sectional study determines the prevalence of lifestyle-related cardiovascular risk factors in heterozygous familial hypercholesterolaemia (HeFH) from the Dyslipidaemia Registry of the Spanish Atherosclerosis Society and in the ENRICA study, a representative sample of the adult Spanish general population, weighted to match the age and sex distribution of the HeFH sample. A total of 2185 HeFH patients and 11,856 individuals from ENRICA were included. HeFH had lower body mass index and fewer of them were smokers than in the reference population. A model adjusted for age, sex and body mass index showed that HeFH more frequently had cardiovascular disease (odds ratio (OR) 23.98; 95% confidence interval (CI) 18.40-31.23) and hypertension (OR 1.20; 95% CI 1.07-1.35), and took anti-hypertensive medication (OR 1.36; 95% CI 1.18-1.56) and anti-diabetic medication (OR 1.25; 95% CI 1.00-1.56), but less frequently were smokers (OR 0.79; 95% CI 0.71-0.89). In a HeFH subsample ( = 513) with complete blood glucose information, those patients without cardiovascular disease showed lower prevalence of smoking and type 2 diabetes mellitus, lower body mass index and glucose, and higher diastolic blood pressure than the Spanish population. The differences in type 2 diabetes mellitus were justified mostly by the difference in body mass index. Body mass index adjustment also showed higher prevalence of hypertension and use of anti-hypertensive drugs in HeFH. In summary, HeFH patients had lower body mass index, which may contribute to explaining the lower prevalence of diabetes, and lower current smoking but higher hypertension.
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http://dx.doi.org/10.1177/2047487319896138DOI Listing
October 2020

Aortic Valvular Disease in Elderly Subjects with Heterozygous Familial Hypercholesterolemia: Impact of Lipid-Lowering Therapy.

J Clin Med 2019 Dec 14;8(12). Epub 2019 Dec 14.

Lipid Unit, Hospital Universitario Miguel Servet, IIS Aragón, CIBERCV, 50009 Zaragoza, Spain.

Hypercholesterolemia and statins are risk factors for aortic stenosis (AS) and vascular calcification, respectively. Whether heterozygous subjects with familial hypercholesterolemia (HeFH) treated with statins are at risk of AS is unknown. We study the prevalence of AS, aortic valve calcification (AoVC), and aortic sclerosis (ASc) in elderly subjects with HeFH in a prolonged statin treatment. Case-control study, cases were adults ≥65 years of age with a genetic diagnosis of HeFH, LDLc >220 mg/dl, and statin treatment ≥5 years. Controls were relatives of HeFH patients, with LDLc <190 mg/dl. Participants underwent a cardiac ultrasound for aortic valve analysis. We studied 205 subjects, 112 HeFH and 93 controls, with mean age 71.8(6.5) years and 70.0(7.3) years, respectively. HeHF, with respect to controls, presented greater gradients of aortic transvalvular pressure, 7.4(7.3) mmHg versus 5.0(2.8) mmHg, and maximum aortic velocity, 1.7(0.7) m/s versus 1.5(0.4) m/s, and lower aortic valve opening area, 2.0(0.7) cm versus 2.4(0.6) cm (all < 0.05). AoVC and ASc were also more prevalent in HeFH ( < 0.05 between groups). Moderate/severe AS prevalence was higher among HeFH: 7.1% versus 1.1% (age- and sex-adjusted odds ratio (OR) 8.33, = 0.03). Independent risk factors for aortic valve disease in HeFH were age and LDLc before treatment. The number of years under statin treatment was not associated with any aortic valve measurement. Subjects ≥65 years with HeFH in prolonged statin treatment show more aortic valvular disease and higher frequency of AS than controls. Life-long elevated LDLc exposure, rather than time of exposure to statins, explains this higher risk.
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http://dx.doi.org/10.3390/jcm8122209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947617PMC
December 2019

LDL-cholesterol: The lower the better.

Clin Investig Arterioscler 2019 Dec 6;31 Suppl 2:16-27. Epub 2019 Dec 6.

Unitat de Lípids i Risc Vascular, Servei de Medicina Interna, Hospital Universitari de Bellvitge, Universitat de Barcelona, Fipec. CiberObn, Barcelona, España. Electronic address:

The reduction of low density lipoprotein-cholesterol (LDL-chol) has been associated with a decrease in cardiovascular morbidity and mortality. It has been demonstrated that there is no value of LDL-chol below which there ceases to be a preventive benefit with its reduction, and neither has it been observed that there is a higher incidence of secondary effects associated with lower concentrations of LDL-chol. Although there is a wide range of lipid-lowering drugs available, a high percentage of patients do not achieve the desired LDL-chol levels. The high-potency statins reduce the LDL-chol by 15-30%, and can double the percentage of patients that reach their desired level. This combination has shown to be safe and effective in the primary and secondary prevention of cardiovascular disease. Another option is the combination of statins with exchange resins, although this requires a more complex management. The inhibition of PCSK9 protein with monoclonal antibodies reduces the LDL-chol by more than 60%, and is effective in the prevention of cardiovascular disease. However, due to its cost, its use is restricted to patients with ischaemia or familial hypercholesterolaemia that do not achieve the desired levels with conventional drugs. The evidence base as regards the benefit and safety of achieving the desired levels of LDL-chol is very wide and is still increasing. In the next few years, it may be necessary to adjust the intensity of the hypercholesterolaemia treatment to the level of vascular risk of the patients, and to the level of reduction necessary to achieve the therapeutic targets. This will result in a more effective cardiovascular prevention and in a better quality of life, particularly in the large group of patients at higher vascular risk.
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http://dx.doi.org/10.1016/j.arteri.2019.10.003DOI Listing
December 2019

Non-HDL cholesterol as a therapeutic goal.

Clin Investig Arterioscler 2019 Dec 2;31 Suppl 2:28-33. Epub 2019 Dec 2.

Grupo de Trabajo sobre la Dislipidemia Aterogénica de la Sociedad Española de Arteriosclerosis, España; Unidad de Lípidos y Riesgo Vascular, Servicio de Medicina Interna, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, España; Institut d'Investigació Biomèdica de Bellvitge (Idibell), Centre d'Investigació Biomèdica en Xarxa-Fisiopatologia de l'Obesitat i la Nutrició (CiberObn), L'Hospitalet de Llobregat, Barcelona, España.

Although cholesterol linked to low-density lipoproteins (c-LDL) is well established as a risk factor for cardiovascular disease, there is often a more complex dyslipidaemia pattern that contributes to the formation of atherosclerotic plaque. Non-HDL cholesterol (c-NO-HDL) is used to estimate the total amount of atherogenic lipoproteins in plasma, some of which are not usually determined in daily clinical practice. c-NO-HDL is easily calculated from the subtraction of total plasma cholesterol from the cholesterol content carried by high density lipoproteins. The c-NO-HDL has a predictive value superior to that of C-LDL to estimate the risk of major cardiovascular events in epidemiological studies. Genetic studies by analysis of the complete genome, together with those based on Mendelian randomisation, point to the aetiological character of c-NO-HDL on ischaemic heart disease (IHD). Intervention studies, and the meta-analyses derived from them, close the causal circle between c-NO-HDL and IHD, by demonstrating that any intervention that decreases the concentrations of the former reduces the incidence of arteriosclerotic heart disease. The European ESC/EAS 2016 guide for the management of dyslipidaemia considers c-NO-HDL as a therapeutic target with a Class IIa recommendation (should be performed) Level B (data from a single randomised clinical trial [RCT]) or from several non-RCTs), and sets its target at less than 100 or 130mg/dL for those patients with very high risk or high risk, respectively. These achievable c-NO-HDL values are easily calculated by adding 30mg/dL to the c-LDL targets.
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http://dx.doi.org/10.1016/j.arteri.2019.07.002DOI Listing
December 2019

Specific Nuclear Magnetic Resonance Lipoprotein Subclass Profiles and Central Arterial Stiffness in Type 1 Diabetes Mellitus: A Case Control Study.

J Clin Med 2019 Nov 5;8(11). Epub 2019 Nov 5.

Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; (CIBERDEM), Instituto de Salud Carlos III, 8029 Madrid, Spain.

Background: Dyslipidemia has been associated with vascular complications of type 1 diabetes mellitus (T1DM). We examined the proton nuclear magnetic resonance (NMR)-assessed lipoprotein subclass profiles in subjects with T1DM compared with those of healthy subjects and assessed the potential relationship of these profiles with arterial stiffness.

Methods: Eighty-four participants with T1DM of at least 10 years duration and no clinical cardiovascular disease (age: 35-65 years; 50% men) and 42 healthy participants were evaluated for: (1) clinical and anthropometric data (including classical cardiovascular risk factors), (2) insulin sensitivity by estimated glucose disposal rate, (3) microvascular complications, (4) NMR-assessed lipoprotein subclass profile, and (5) arterial stiffness (aortic pulse wave velocity).

Results: Participants with T1DM had an apparently better conventional lipid profile than healthy participants, but with significant differences in NMR-assessed lipoprotein profiles such as higher triglyceride content of low-density lipoprotein (LDL) and high-density lipoprotein (HDL). In healthy participants, arterial stiffness was associated with NMR-based LDL subclasses. By contrast, in T1DM participants, arterial stiffness was independently associated mainly with NMR-based very-low-density lipoprotein (VLDL) subclasses: positively with total VLDL particles (and subclasses) and VLDL triglyceride content, and negatively with LDL and HDL particle sizes. These results were maintained after adjustments for classical cardiovascular risk factors.

Conclusions: Subjects with T1DM, while having an apparently better conventional lipid profile than healthy controls, presented significant alterations in their NMR-assessed lipoprotein profile. The association between arterial stiffness and NMR-assessed lipoprotein profiles also differed in both groups. These results support a potential role of the identified differences in the residual cardiovascular risk in T1DM.
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http://dx.doi.org/10.3390/jcm8111875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912486PMC
November 2019
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