Metabolic syndrome and cholangiocarcinoma: large numbers, small risks, but big implications.

Metabolic Syndrome

Children with psoriasis are at increased risk for comorbidities. Many children with psoriasis are also overweight or obese; it is unknown whether the increased risk of comorbidities in these children is independent of obesity. To determine the risk of elevated lipid levels (hyperlipidemia/hypertriglyceridemia), hypertension, metabolic syndrome, polycystic ovarian syndrome, diabetes, nonalcoholic liver disease, and elevated liver enzyme levels in children with and without psoriasis, after accounting for obesity. This was a retrospective cohort study of claims data from Optum Laboratories Data Warehouse (includes 150 million privately insured and Medicare enrollees). A cohort of 29 957 children with psoriasis (affected children) and an age-, sex-, and race-matched comparator cohort of 29 957 children without psoriasis were identified and divided into 4 groups: (1) nonobese, without psoriasis (reference cohort); (2) nonobese, with psoriasis; (3) obese, without psoriasis; and (4) obese, with psoriasis. Risk of developing comorbidities (Cox proportional hazards regression). The overall mean (SD) age of those included in the cohort was 12.0 (4.4) years, and 16 034 (53.5%) were girls. At baseline, more affected children were obese (862 [2.9%] vs 463 [1.5%]; P < .001 for all comparisons). Children with psoriasis were significantly more likely to develop each of the comorbidities than those without psoriasis (P < .01). Obesity was a strong risk factor for development of each comorbidity, even in those without psoriasis (hazard ratios [HRs] ranging from 2.26 to 18.11). The risk of comorbidities was 40% to 75% higher among nonobese children with vs without psoriasis: elevated lipid levels (HR, 1.42; 95% CI, 1.25-1.62), hypertension (HR, 1.64; 95% CI, 1.40-1.93), diabetes (HR, 1.58; 95% CI, 1.27-1.95), metabolic syndrome (HR, 1.62; 95% CI, 1.13-2.33), polycystic ovarian syndrome (HR, 1.49; 95% CI, 1.18-1.88), nonalcoholic liver disease (HR, 1.76; 95% CI, 1.16-2.65), and elevated liver enzyme levels (HR, 1.46; 95% CI, 1.27-1.67). Except for hypertension (P = .03), no significant interaction occurred between psoriasis and obesity on the risk of comorbidities. Children with psoriasis are at greater risk of developing obesity, hyperlipidemia, hypertension, diabetes, metabolic syndrome, polycystic ovarian syndrome, nonalcoholic liver disease, and elevated liver function enzyme levels than children without psoriasis. While psoriasis is a small independent risk factor for the development of these comorbidities, obesity is a much stronger contributor to comorbidity development in children with psoriasis.

Charles D. Collard, MD In this issue of Anesthesia & Analgesia, Le Manach et al. add to the growing evidence that perioperative statin therapy reduces surgical morbidity and mortality (1–6). Moreover, data from these same authors and others suggest that postoperative discontinuation of statin therapy is associated with worsened cardiac outcomes after major cardiovascular surgery (1,2). Thus, administration of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or “statins,” may be one of the most important perioperative therapeutic regimens to reduce the risk of postoperative cardiovascular complications in high-risk surgical patients since the introduction of -blockers into the operative setting (6). However, unlike the situation with perioperative -blocker therapy, the American College of Cardiology/American Heart Association Task Force on Practice Guidelines have yet to publish a consensus statement regarding perioperative statin therapy. Current National Cholesterol Education Program Adult Treatment Panel guidelines recommend decreasing LDL levels to 100 mg/dL in patients with known coronary disease, and more aggressive statin therapy to decrease LDL levels to 70 mg/dL in patients with coronary disease and high risk factors such as diabetes, hypertension, obesity, smoking, the metabolic syndrome, and acute coronary syndromes (ACS) (7). Thus, on the basis of these guidelines, most patients undergoing major cardiovascular surgery would qualify for statin therapy. Yet, despite these guidelines, it is estimated that up to two-thirds of eligible candidates may not be receiving statin therapy at hospital discharge (8). Explanations for not starting or reinitiating statin therapy after cardiovascular surgery may include patients’ decreased tolerance of oral medications secondary to nausea and vomiting, transient renal dysfunction, concerns pertaining to hepatic toxicity or myositis, or failure of the responsible physician to reimplement preoperative medications. The most serious potential statin side effect is rhabdomyolysis. Cerivastatin, which is no longer on the market, carried the greatest risk of this complication (3.16 per million prescriptions). In contrast, the risk of statin-induced rhabdomyolysis ranges only from 0 to 0.19 per million prescriptions for the other commonly used statins (9). Furthermore, the risk for rhabdomyolysis is associated with factors that increase serum statin concentrations, such as small body size, advanced age, renal or hepatic dysfunction, diabetes, hypothyroidism, and drugs that interfere with statin metabolism, such as cyclosporin, antifungal drugs, calciumchannel blockers, and amiodarone (9). When this small risk is compared with the incidence and socioeconomic cost of cardiac perioperative morbidity and mortality after major cardiovascular surgery, the benefits of statin therapy seem to largely outweigh any potential risks in the vast majority of patients. Moreover, in a recent study by Schouten et al., perioperative statin use in a large group of patients was not associated with an increased risk of perioperative myopathy or increased creatine phosphokinase levels after major vascular surgery (10). Indeed, after correcting for cardiac risk factors and clinical risk factors for myopathy, length of surgery remained the only independent predictor for myopathy From the Division of Cardiovascular Anesthesiology, Baylor College of Medicine, Texas Heart Institute, St. Luke’s Episcopal Hospital, Houston, Texas. Accepted for publication March 6, 2007. Address correspondence to Charles D. Collard, MD, Baylor College of Medicine, Texas Heart Institute, St. Luke’s Episcopal Hospital, 6720 Bertner Ave., Houston, TX 77030. Address e-mail to ccollard@heart.thi. tmc.edu. Copyright © 2007 International Anesthesia Research Society

Mutations in the small heterodimer partner gene (NR0B2; alias SHP) are associated with high birth weight and mild obesity in Japanese children. SHP mutations may also be associated with later obesity and insulin resistance syndrome that induces diabetes. To investigate this possibility, the prevalence of SHP mutations in Japanese with and without type 2 diabetes mellitus and the functional properties of the mutant proteins were evaluated. Direct sequencing of two exons and flanking sequences of SHP in 805 diabetic patients and 752 non-diabetic controls identified 15 different mutations in 44 subjects, including 6 novel mutations. Functional analyses of the mutant proteins revealed significantly reduced activity of nine of the mutations. Mutations with reduced activity were found in 19 patients (2.4%) in the diabetic group and in 6 subjects (0.8%) in the control group. The frequency difference between DM and control subjects adjusted for sex and age was statistically significant (P=0.029, odds ratio 2.67, 95% CI 1.05-6.81, 1-beta=0.91). We conclude that SHP mutations associated with mild obesity in childhood increase susceptibility to type 2 diabetes in later life in Japanese.

Short sleep is a questionable risk factor for obesity and related disorders: Statistical versus clinical significance

Why is transient elastography essential in hepatology?

Small dense LDL, metabolic syndrome and coronary risk

To discuss the relevance of triglycerides to cardiovascular disease (CVD) risk. Triglycerides are a commonly measured component of lipid profiles. Raised triglycerides are a component of the metabolic syndrome and are strongly associated with future risk of diabetes as well as cardiovascular disease. Triglyceride-rich particles form a component of cardiovascular risk above that delineated by low density lipoprotein (LDL) cholesterol. Elevated triglycerides are a marker of atherogenic small dense LDL, excess baseline and residual CVD risk even after statin therapy. Additional methods to lower triglycerides include niacin, fibrates and omega-3 fatty acids. Trials in monotherapy with both niacin and fibrates suggest some benefit in reducing CVD events based on evidence mostly derived from older studies. However, endpoint trials of adding either niacin or fenofibrate to statins have not shown any benefit, except possibly in patients with an increased atherogenic index (triglyceride : HDL-C ratio), or have been underpowered. Trials of omega-3 fatty acids have been performed at doses insufficient to affect lipid profiles in populations with inadequate control of LDL-C but did reduce CVD events. Further trials of lipid-lowering agents beyond statins will be required in patients with LDL-C adequately controlled on statin therapy.

Few studies have examined the relationship between cardiometabolic risk factors linked to metabolic syndrome and mortality among women with breast cancer. We used the Women's Health Initiative to evaluate the relationship between cardiometabolic risk factors, including waist circumference (WC), blood pressure, cholesterol level, and presence of type 2 diabetes, and their relation with death from breast cancer, cardiovascular disease (CVD), and other causes among 8641 women with local or regional stage invasive breast cancer. Cox proportional hazards models were used to estimate hazard ratios, and 95% confidence intervals, adjusted for important predictors of survival. After a median of 11.3 years, there were 2181 total deaths, 619 (28.4%) of which were due to breast cancer. Most participants (55.7%) had at least 2 cardiometabolic risk factors, and 4.9% had 3 or 4. Having a larger number of risk factors was associated with higher risk of CVD and other-cause mortality (P trend < .001 for both), but not with breast cancer mortality (P trend = .86). Increased WC was associated with a higher risk of CVD (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.05-1.57) and other-cause mortality (HR, 1.32; 95% CI, 1.16-1.49) and only with a small and nonsignificant higher risk of breast cancer mortality (HR, 1.19; 95% CI, 0.93-1.52). The results did not differ in analyses stratified by race, hormone receptor status, or after an analysis of cases diagnosed within 5 years after baseline. Among women with early stage breast cancer, cardiometabolic risk factors are significantly associated with cardiovascular and other-cause mortality, but not breast cancer mortality. Cancer 2018;124:1798-807. © 2018 American Cancer Society.

From the Editor’s Desk…: October 2018