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Plasma Omega-3 Fatty Acids and the Risk of Cardiovascular Events in Patients After an Acute Coronary Syndrome in MERLIN-TIMI 36.
Zelniker, TA, Morrow, DA, Scirica, BM, Furtado, JD, Guo, J, Mozaffarian, D, Sabatine, MS, O'Donoghue, ML
Journal of the American Heart Association. 2021;(8):e017401
Abstract
Background Plasma omega-3 polyunsaturated fatty acids (ω3-PUFAs) have been shown to be inversely correlated with the risk of cardiovascular death in primary prevention. The risk relationship in the setting of an acute coronary syndrome is less well established. Methods and Results Baseline plasma ω3-PUFA composition (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) was assessed through gas chromatography with flame ionization detection in a case-cohort study involving 203 patients with cardiovascular death, 325 with myocardial infarction, 271 with ventricular tachycardia, and 161 with atrial fibrillation, and a random sample of 1612 event-free subjects as controls from MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation-Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36), a trial of patients hospitalized with non-ST-segment-elevation -acute coronary syndrome. After inverse-probability-weighted multivariable adjustment including all traditional risk factors, a higher relative proportion of long-chain ω3-PUFAs (eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid) were associated with 18% lower odds of cardiovascular death (adjusted [adj] odds ratio [OR] per 1 SD, 0.82; 95% CI, 0.68-0.98) that was primarily driven by 27% lower odds of sudden cardiac death (adj OR per 1 SD, 0.73; 95% CI, 0.55-0.97). Long-chain ω3-PUFA levels in the top quartile were associated with 51% lower odds of cardiovascular death (adj OR 0.49; 95% CI, 0.27-0.86) and 63% lower odds of sudden cardiac death (adj OR, 0.37; 95% CI, 0.16-0.56). An attenuated relationship was seen for α-linolenic acid and subsequent odds of cardiovascular (adj OR, 0.92; 95% CI, 0.74-1.14) and sudden cardiac death (adj OR, 0.91; 95% CI, 0.67-1.25). No significant relationship was observed between any ω3-PUFAs and the odds of cardiovascular death unrelated to sudden cardiac death, myocardial infarction, atrial fibrillation, or early post-acute coronary syndrome ventricular tachycardia. Conclusions In patients after non-ST-segment-elevation-acute coronary syndrome, plasma long-chain ω3-PUFAs are inversely associated with lower odds of sudden cardiac death, independent of traditional risk factors and lipids. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00099788.
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Hiding unhealthy heart outcomes in a low-fat diet trial: the Women's Health Initiative Randomized Controlled Dietary Modification Trial finds that postmenopausal women with established coronary heart disease were at increased risk of an adverse outcome if they consumed a low-fat 'heart-healthy' diet.
Noakes, TD
Open heart. 2021;(2)
Abstract
The Women's Health Initiative Randomized Controlled Dietary Modification Trial (WHIRCDMT) was designed to test whether the US Department of Agriculture's 1977 Dietary Guidelines for Americans protects against coronary heart disease (CHD) and other chronic diseases. The only significant finding in the original 2006 WHIRCDMT publication was that postmenopausal women with CHD randomised to a low-fat 'heart-healthy' diet in 1993 were at 26% greater risk of developing additional CHD events compared with women with CHD eating the control diet. A 2017 WHIRCDMT publication includes data for an additional 5 years of follow-up. It finds that CHD risk in this subgroup of postmenopausal women had increased further to 47%-61%. The authors present three post-hoc rationalisations to explain why this finding is 'inadmissible': (1) only women in this subgroup were less likely to adhere to the prescribed dietary intervention; (2) their failure to follow the intervention diet increased their CHD risk; and (3) only these women were more likely to not have received cholesterol-lowering drugs. These rationalisations appear spurious. Rather these findings are better explained as a direct consequence of postmenopausal women with features of insulin resistance (IR) eating a low-fat high-carbohydrate diet for 13 years. All the worst clinical features of IR, including type 2 diabetes mellitus (T2DM) in some, can be 'reversed' by the prescription of a high-fat low-carbohydrate diet. The Women's Health Study has recently reported that T2DM (10.71-fold increased risk) and other markers of IR including metabolic syndrome (6.09-fold increased risk) were the most powerful predictors of future CHD development in women; blood low-density lipoprotein-cholesterol concentration was a poor predictor (1.38-fold increased risk). These studies challenge the prescription of the low-fat high-carbohydrate heart-healthy diet, at least in postmenopausal women with IR, especially T2DM. According to the medical principle of 'first do no harm', this practice is now shown to be not evidence-based, making it scientifically unjustifiable, perhaps unethical.
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Testosterone concentrations and risk of cardiovascular events in androgen-deficient men with atherosclerotic cardiovascular disease.
Boden, WE, Miller, MG, McBride, R, Harvey, C, Snabes, MC, Schmidt, J, McGovern, ME, Fleg, JL, Desvigne-Nickens, P, Anderson, T, et al
American heart journal. 2020;:65-76
Abstract
BACKGROUND Whether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest. OBJECTIVES Among male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up. METHODS In this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL ["low T"] vs. ≥300 ng/dL ["normal T"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models. RESULTS Among 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively. CONCLUSIONS In this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke. CONDENSED ABSTRACT In this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The "low T" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively.
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Metabolic Syndrome Predicts Worse Perioperative Outcomes in Patients Treated With Partial Nephrectomy for Renal Cell Carcinoma.
Luzzago, S, Palumbo, C, Rosiello, G, Pecoraro, A, Deuker, M, Stolzenbach, F, Mistretta, FA, Tian, Z, Musi, G, Montanari, E, et al
Urology. 2020;:91-97
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Abstract
OBJECTIVE To test the association between metabolic syndrome (MetS) and its components (high blood pressure, body mass index [BMI] ≥ 30, altered fasting glucose, low high-density lipoprotein cholesterol and high triglycerides) on perioperative outcomes after partial nephrectomy (PN). METHODS Within the National Inpatient Sample database (2000-2015) we identified all PN patients. First, temporal trends of MetS were reported. Second, the effect of MetS components was tested in multivariable logistic regression models predicting overall and specific perioperative complications. Third, we tested for dose-response from the concomitant effect of multiple MetS components. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics. RESULTS Of 25,875 patients: (1) 59.3% had high blood pressure, (2) 14.7% had BMI ≥ 30, (3) 21.7% had altered fasting glucose, (4) 20.2% had high triglycerides, and (5) <0.01% had low high-density lipoprotein cholesterol. One vs 2 vs 3 vs 4 MetS components were recorded in 34.9% vs 22.9% vs 8.9% vs 2.2% patients. Of all, 11.1% exhibited ≥ 3 components and qualified for MetS. The rates of MetS increased over time (estimated annual percentage changes: +12.0%;P <.001). The 4 tested MetS components (high blood pressure, BMI ≥ 30, altered fasting glucose, and high triglycerides) achieved independent predictor status in multivariable models predicting overall, cardiac, miscellaneous medical, vascular, and respiratory complications, as well as transfusions. Moreover, a statistically significant dose-response was confirmed for the same endpoints. CONCLUSION MetS and its components consistently and strongly predict perioperative complications after PN. Moreover, the strength of the effect was directly proportional to the number of MetS components exhibited by each individual patient, even if formal MetS diagnosis of ≥ 3 components has not been met.
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Does chronic hyperglycaemia increase the risk of kidney stone disease? results from a systematic review and meta-analysis.
Geraghty, R, Abdi, A, Somani, B, Cook, P, Roderick, P
BMJ open. 2020;(1):e032094
Abstract
DESIGN Systematic review and meta-analysis of observational studies was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for studies reporting on diabetes mellitus (DM) or metabolic syndrome (MetS) and kidney stone disease (KSD). OBJECTIVE To examine the association between chronic hyperglycaemia, in the form of DM and impaired glucose tolerance (IGT) in the context of MetS and KSD. SETTING Population-based observational studies. Databases searched: Ovid MEDLINE without revisions (1996 to June 2018), Cochrane Library (2018), CINAHL (1990 to June 2018), ClinicalTrials.gov, Google Scholar and individual journals including the Journal of Urology, European Urology and Kidney International. PARTICIPANTS Patients with and without chronic hyperglycaemic states (DM and MetS). MAIN OUTCOME MEASURES English language articles from January 2001 to June 2018 reporting on observational studies. EXCLUSIONS No comparator group or fewer than 100 patients. Unadjusted values were used for meta-analysis, with further meta-regression presented as adjusted values. Bias was assessed using Newcastle-Ottawa scale. RESULTS 2340 articles were screened with 13 studies included for meta-analysis, 7 DM (three cohort) and 6 MetS. Five of the MetS studies provided data on IGT alone. These included: DM, n=28 329; MetS, n=31 767; IGT, n=12 770. CONTROLS DM, n=5 89 791; MetS, n=1 78 050; IGT, n=2 93 852 patients. Adjusted risk for DM cohort studies, RR=1.23 (0.94 to 1.51) (p<0.001). Adjusted ORs for: DM cross-sectional/case-control studies, OR=1.32 (1.21 to 1.43) (p<0.001); IGT, OR=1.26 (0.92 to 1.58) (p<0.0001) and MetS, OR=1.35 (1.16 to 1.54) (p<0.0001). There was no significant difference between IGT and DM (cross-sectional/case-control), nor IGT and MetS. There was a moderate risk of publication bias. Statistical heterogeneity remained significant in adjusted DM cohort values and adjusted IGT (cross-sectional/case-control), but non-signficant for adjusted DM (cross-sectional/case-control). CONCLUSION Chronic hyperglycaemia increases the risk of developing kidney stone disease. In the context of the diabetes pandemic, this will increase the burden of stone related morbidity and mortality. PROSPERO REGISTRATION NUMBER CRD42018093382.
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Prediction and early detection of cardiovascular disease in South Asians with diabetes mellitus.
Wander, GS, Bansal, M, Kasliwal, RR
Diabetes & metabolic syndrome. 2020;(4):385-393
Abstract
BACKGROUND Although diabetes mellitus (DM) is no longer considered "coronary heart disease risk equivalent", the risk remains sufficiently high, necessitating early recognition and management of cardiovascular disease (CVD) in these patients. Despite this understanding, the optimum strategy for prediction and early detection of CVD in DM remains debatable. METHODS Major societal guidelines for prediction and evaluation of CVD in subjects with or without DM were reviewed. Available evidence about various risk stratification strategies-their advantages, disadvantages and current role in clinical practice-were extensively reviewed. Special emphasis was placed on evidence from South Asian/Indian populations. RESULTS The inconsistency and variability inherent to the clinical risk algorithms, lack of consensus regarding the incremental value of subclinical atherosclerosis imaging and the lack of sufficient data to demonstrate the benefits of recognizing asymptomatic atherosclerotic disease are some of the reasons underlying prevailing uncertainty about the optimum approach for cardiovascular risk assessment in DM. These challenges notwithstanding, an evidence-based cardiovascular risk stratification strategy incorporating clinical risk algorithms, biomarkers, atherosclerosis imaging, and cardiac stress testing is proposed. CONCLUSIONS The proposed algorithm should help clinicians in optimizing cardiovascular evaluation and management of their patients with DM. However, this remains a dynamic field; further research into different risk assessment tools, esp. focusing on their impact on improving clinical outcomes, should help refine the evaluation strategy in future.
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Development and validation of a predictive model for incident type 2 diabetes in middle-aged Mexican adults: the metabolic syndrome cohort.
Arellano-Campos, O, Gómez-Velasco, DV, Bello-Chavolla, OY, Cruz-Bautista, I, Melgarejo-Hernandez, MA, Muñoz-Hernandez, L, Guillén, LE, Garduño-Garcia, JJ, Alvirde, U, Ono-Yoshikawa, Y, et al
BMC endocrine disorders. 2019;(1):41
Abstract
BACKGROUND Type 2 diabetes mellitus (T2D) is a leading cause of morbidity and mortality in Mexico. Here, we aimed to report incidence rates (IR) of type 2 diabetes in middle-aged apparently-healthy Mexican adults, identify risk factors associated to ID and develop a predictive model for ID in a high-risk population. METHODS Prospective 3-year observational cohort, comprised of apparently-healthy adults from urban settings of central Mexico in whom demographic, anthropometric and biochemical data was collected. We evaluated risk factors for ID using Cox proportional hazard regression and developed predictive models for ID. RESULTS We included 7636 participants of whom 6144 completed follow-up. We observed 331 ID cases (IR: 21.9 per 1000 person-years, 95%CI 21.37-22.47). Risk factors for ID included family history of diabetes, age, abdominal obesity, waist-height ratio, impaired fasting glucose (IFG), HOMA2-IR and metabolic syndrome. Early-onset ID was also high (IR 14.77 per 1000 person-years, 95%CI 14.21-15.35), and risk factors included HOMA-IR and IFG. Our ID predictive model included age, hypertriglyceridemia, IFG, hypertension and abdominal obesity as predictors (Dxy = 0.487, c-statistic = 0.741) and had higher predictive accuracy compared to FINDRISC and Cambridge risk scores. CONCLUSIONS ID in apparently healthy middle-aged Mexican adults is currently at an alarming rate. The constructed models can be implemented to predict diabetes risk and represent the largest prospective effort for the study metabolic diseases in Latin-American population.
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Adherence to an Energy-restricted Mediterranean Diet Score and Prevalence of Cardiovascular Risk Factors in the PREDIMED-Plus: A Cross-sectional Study.
Álvarez-Álvarez, I, Martínez-González, MÁ, Sánchez-Tainta, A, Corella, D, Díaz-López, A, Fitó, M, Vioque, J, Romaguera, D, Martínez, JA, Wärnberg, J, et al
Revista espanola de cardiologia (English ed.). 2019;(11):925-934
Abstract
INTRODUCTION AND OBJECTIVES The cardiovascular benefits of the Mediterranean diet have usually been assessed under assumptions of ad libitum total energy intake (ie, no energy restriction). In the recently launched PREDIMED-Plus, we conducted exploratory analyses to study the baseline associations between adherence to an energy-restricted Mediterranean diet (MedDiet) and the prevalence of cardiovascular risk factors (CVRF). METHODS Cross-sectional assessment of all PREDIMED-Plus participants (6874 older adults with overweight/obesity and metabolic syndrome) at baseline. The participants were assessed by their usual primary care physicians to ascertain the prevalence of 4 CVRF (hypertension, obesity, diabetes, and dyslipidemia). A 17-point PREDIMED-Plus score was used to measure adherence to the MedDiet. Multivariable models were fitted to estimate differences in means and prevalence ratios for individual and clustered CVRF. RESULTS Better adherence to a MedDiet pattern was significantly associated with lower average triglyceride levels, body mass index, and waist circumference. Compared with low adherence (≤ 7 points in the 17-point score), better adherence to the MedDiet (11-17 points) showed inverse associations with hypertension (prevalence ratio=0.97; 95%CI, 0.94-1.00) and obesity (prevalence ratio=0.96; 95%CI, 0.92-1.00), but positive associations with diabetes (prevalence ratio=1.19; 95%CI, 1.07-1.32). Compared with the lowest third of adherence, women in the upper third showed a significantly lower prevalence of the clustering of 3 or more CVRF (prevalence ratio=0.91; 95%CI, 0.83-0.98). CONCLUSIONS Among participants at high cardiovascular risk, better adherence to a MedDiet showed significant inverse associations with CVRF among women, and improved lipid profiles and adiposity measures. This trial was registered in 2014 at the International Standard Randomized Controlled Trial Registry (ISRCTN89898870).
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A stage-dependent link between metabolic syndrome components and incident prostate cancer.
Hammarsten, J, Damber, JE, Haghsheno, MA, Mellström, D, Peeker, R
Nature reviews. Urology. 2018;(5):321-333
Abstract
Metabolic syndrome is associated with increased cancer risk and progression at almost all sites, including the prostate in high-stage prostate cancer. However, several reports have described an inverse relationship between metabolic syndrome and its components and low-stage incident prostate cancer. Such anomalies in cancer research hamper efforts to fight cancer. Evidence suggests that metabolic syndrome and its components have two distinct effects in prostate cancer, concealing prostate cancer in low-stage disease and promoting progression to high-stage incident, nonlocalized, and lethal prostate cancer. The concealment of prostate cancer by metabolic syndrome and its components might be related to bias mechanisms that reduce PSA level and lead to a delayed diagnosis of low-stage prostate cancer, meaning that fewer men with metabolic syndrome are diagnosed with low-stage disease. The inverse link between metabolic syndrome and its components and low-stage incident prostate cancer might simply be the result of such bias and the shortcomings of the diagnostic procedure rather than being related to prostate cancer biology itself. The evidence summarized here supports the hypothesis that the link between metabolic syndrome and its components and incident prostate cancer is a two-way and stage-dependent one, a theory that requires further research.
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Is the metabolic syndrome inversely associates with butter, non-hydrogenated- and hydrogenated-vegetable oils consumption: Tehran lipid and glucose study.
Hosseinpour-Niazi, S, Mirmiran, P, Hosseini-Esfahani, F, Azizi, F
Diabetes research and clinical practice. 2016;:20-29
Abstract
AIM: The aim of this study was to investigate the association between hydrogenated- (HVOs) and non-hydrogenated vegetable oils (non-HVOs) and butter and the metabolic syndrome (MetS) after 3-years of follow-up in adults. METHODS This study was conducted between 2006-2008 and 2009-2011 within the framework of the Tehran Lipid and Glucose Study, on 1582 adults, aged 19-84 years. Intakes of HVOs, non-HVOs and butter were assessed by a validated semi-quantitative food frequency questionnaire. Based on the consumption of food rich in fat including HVOs, non-HVOs and butter, participants were categorized to consumers and non-consumers. RESULTS Of 1582 participants during a 3-year follow-up, 15.2% developed MetS. Non-consumption of butter was associated with lower MetS risk compared with its consumption. Among consumers of food rich in fat, intake of HVOs and butter were associated with an increased risk of MetS; ORs in the final multivariate model were 2.70 (95% CI: 1.52-4.78) for HVOs and 2.03 (95% CI: 1.20-3.41) for butter, in the highest, compared to the lowest category of dietary intakes. Intake of non-HVOs was not associated with risk of MetS. CONCLUSIONS Consumption of HVOs and butter were positively associated with an increase risk of MetS.