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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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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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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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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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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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Relationship of the metabolic syndrome to carotid ultrasound traits.
Pollex, RL, Al-Shali, KZ, House, AA, Spence, JD, Fenster, A, Mamakeesick, M, Zinman, B, Harris, SB, Hanley, AJ, Hegele, RA
Cardiovascular ultrasound. 2006;:28
Abstract
BACKGROUND The metabolic syndrome is associated with increased vascular disease risk. We evaluated two carotid ultrasound measurements, namely intima media thickness and total plaque volume, in a Canadian Oji-Cree population with a high metabolic syndrome prevalence rate. METHODS As part of the Sandy Lake Complications Prevalence and Risk Factor Study, 166 Oji-Cree subjects (baseline metabolic syndrome prevalence, 44.0%, according to the National Cholesterol Education Program Adult Treatment Panel III guidelines) were examined using a high-resolution duplex ultrasound scanner. RESULTS Image analysis showed that mean intima media thickness was elevated in subjects with the metabolic syndrome (818 +/- 18 vs 746 +/- 20 microm), as was total plaque volume (125 +/- 26 vs 77.3 +/- 17.0 mm3). However, after adjustment for age and sex, the differences were significant only for intima media thickness (P = 0.039). Furthermore, a significant trend towards increased intima media thickness was observed with increasing numbers of metabolic syndrome components: mean intima media thickness was highest among individuals with all five metabolic syndrome components compared to those with none (866 +/- 55 vs 619 +/- 23 microm, P = 0.0014). A similar, but non-significant trend was observed for total plaque volume. CONCLUSION This is the first study of the relationship between the metabolic syndrome and two distinct carotid ultrasound traits measured in the same individuals. The results suggest that standard intima media thickness measurement shows a more consistent and stronger association with the metabolic syndrome than does total plaque volume.
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Substrate-energy metabolism and metabolic risk factors for cardiovascular disease in relation to fetal growth and adult body composition.
Kensara, OA, Wooton, SA, Phillips, DI, Patel, M, Hoffman, DJ, Jackson, AA, Elia, M, ,
American journal of physiology. Endocrinology and metabolism. 2006;(2):E365-71
Abstract
The effect of fetal programming on intermediary metabolism is uncertain. Therefore, we examined whether fetal programming affects oxidative and nonoxidative macronutrient metabolism and the prevalence of the metabolic syndrome in adult life. Healthy older men, aged 64-72 years, with either a lower birth weight (LBW, or=75th %ile; n = 13) had measurements of 1) net oxidative metabolism using indirect calorimetry before and for 6 h after a mixed meal (3,720 kJ) and 2) postprandial oxidation of exogenous [13C]palmitic acid. Body composition was measured using dual-energy X-ray absorptiometry. After adjustment for current weight and height, the LBW group had a lower resting energy expenditure (REE) in the preprandial (4.01 vs. 4.54 kJ/min, P = 0.015) and postprandial state (4.60 vs. 5.20 kJ/min, P = 0.004), and less fat-free mass than the HBW group. The BW category was a significant, independent, and better predictor of REE than weight plus height. There were no significant differences between groups in net oxidative and nonoxidative macronutrient (protein, fat, carbohydrate) metabolism (or of exogenous [13C]palmitate) or in the prevalence of the metabolic syndrome, which was present almost twice as commonly in the LBW than in the HBW group. The study suggests that fetal programming affects both pre- and postprandial EE in older life by mechanisms that are at least partly related to the mass of the fat-free body. BW was found to be a significant predictor of REE that was independent of adult weight plus height.
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Rising to the challenge of the new NCEP ATP III guidelines: exceeding current therapeutic limitations.
Brewer, HB
The American journal of managed care. 2002;(2 Suppl):S23-8; discussion S45-7
Abstract
The third set of guidelines recently issued by the National Cholesterol Education Program (NCEP) differs from the second set issued in 1993 in several ways. The third set introduced a quantitative risk scoring system and identified and/or reclassified certain groups of patients at high or moderate risk for a coronary event. Among these groups are patients with type 2 diabetes, and patients with multiple risk factors other than coronary heart disease or diabetes that cumulatively confer high risk for a coronary event. However, the new guidelines also present physicians with the major challenges of identifying these patients, determining their true risk, and implementing the recommended approaches to treatment in clinical practice settings. Although reducing elevated levels of low-density lipoprotein (LDL) cholesterol remains the primary focus of therapy, the new NCEP guidelines also include strategies to identify and treat patients with low levels of high-density lipoprotein (HDL) cholesterol and/or elevated triglyceride levels. Just as there is "good" cholesterol (HDL) and "bad" cholesterol (LDL), there are also "good" triglycerides, which contain high concentrations of triglyceride remnants and are associated with low risk, and "bad" triglycerides, which contain high concentrations of cholesterol remnants and are associated with increased risk. The mechanisms by which "bad" triglycerides develop explain why elevated triglycerides and low HDL--and patients with the metabolic syndrome--warrant special attention. These mechanisms and others also suggest new targets for therapeutic intervention and the development of new drugs that will correct lipid and lipoprotein abnormalities through a number of different metabolic pathways.