Cardiovascular Characteristics in Subjects With Increasing Levels of Abnormal Glucose Regulation: The Strong Heart Study

OBJECTIVE

To evaluate whether impaired fasting glucose (IFG) or the combination of IFG and impaired glucose tolerance (IGT) is associated with progressive abnormalities of cardiac geometry and function.

RESEARCH DESIGN AND METHODS

We studied 562 nondiabetic (311 women), nonhypertensive participants of the second Strong Heart Study exam, without prevalent cardiovascular (CV) disease and with estimated glomerular filtration rate ≥60 mL/min/1.73 m² (age 46–65 years, 198 with isolated IFG [35%], and 132 with combined IFG and IGT [23%]). Anthropometric parameters, insulin resistance, fibrinogen, C-reactive protein (CRP), lipid profile, blood pressure (BP), and echocardiographic parameters were compared with 232 participants with normal glucose tolerance (NGT).

RESULTS

BMI, prevalence of central obesity, homeostatic model assessment index of insulin resistance, plasma triglycerides, fibrinogen, and CRP increased progressively across categories of glucose intolerance (P < 0.0001), with the IFG+IGT group having higher values than those with isolated IFG (0.05 < P < 0.0001). Compared with NGT, both IFG and IFG+IGT exhibited greater left ventricular (LV) mass (P < 0.0001) and lower Doppler early peak rapid filling velocity to peak atrial filling velocity ratio (P < 0.005), without differences in LV systolic function. The odds of LV hypertrophy (LV mass index >46.7 in women or >49.2 g/m^2.7 in men) was 3.5 in IFG participants (95% CI 0.68–17.76; P = NS) and 9.76 (2.03–46.79; P = 0.004) in IFG+IGT, compared with NGT, after adjustment for age, sex, heart rate, systolic BP, and waist circumference (WC). In the overall sample, LV mass index was associated with WC (P = 0.033), CRP (P = 0.027), and 2-h oral glucose tolerance test (P = 0.001) independently of confounders.

CONCLUSIONS

Cardiometabolic profile and markers of inflammation are more severely altered in men and women with both IFG and IGT compared with those with IFG alone. These individuals, in the absence of hypertension, have a 10-fold greater probability of preclinical CV disease (LV hypertrophy).Diabetes increases the risk of cardiovascular (CV) disease and mortality (1), an association that is independent of other CV risk factors (2). Evidence has also emerged of an increased CV risk in individuals with abnormal glucose regulation (3,4). Both states of abnormal glucose regulation (i.e., impaired fasting glucose [IFG] and impaired glucose tolerance [IGT]) are reported to be associated with excess body weight and increased levels of CV risk factors, morbidity, and mortality (5–7), although these associations are not universally recognized (8,9).Whether increased plasma glucose above the normal range but below that of clinical diabetes has an impact on cardiac geometry and function is little explored. Cohort studies in communities have shown increased left ventricular (LV) mass and remodeling in individuals with prediabetes (10–12), which appear to be mediated by insulin resistance and body fat distribution (11). However, there are limited clinical or population studies examining CV phenotype in individuals with IGT (13,14), and they included participants with hypertension and/or CV disease, making it difficult to evaluate the role of abnormal glucose levels.Glucose dysregulation is a continuum from elevation of either fasting or postprandial glucose concentration to impairment of both and, eventually, to type 2 diabetes. This progression is associated with worsening CV risk profile, and individuals with both IFG and IGT have more severe metabolic abnormalities and a greater risk of conversion to type 2 diabetes than those with isolated IFG or IGT (5). Thus, it is plausible that CV phenotype also may worsen in parallel with more severe glucose impairment. Accordingly, in the population of the Strong Heart Study (SHS), we compared the metabolic and echocardiographic features of nondiabetic participants who had either IFG or IFG and IGT combined from the second exam; we hypothesized that the combination of IFG and IGT is associated with more severe abnormalities of cardiac geometry and function than isolated IFG.     

Insulin Resistance,Incident Cardiovascular Diseases,and Decreased Kidney Function Among Nondiabetic American Indians: The Strong Heart Study

OBJECTIVE

Prevalence of insulin resistance is high in the American Indian population, likely as a result of the high prevalence of obesity. This condition may be influential for clinical outcomes such as cardiovascular disease (CVD) and decreased kidney function.

RESEARCH DESIGN AND METHODS

Normal glucose tolerant (NGT) participants free of hypertension and CVD at the baseline examination (1989–1992) (N = 964) of the Strong Heart Study were selected to explore the cross-sectional association between insulin resistance quantified by homeostasis model assessment (HOMA-IR) and demographic, behavioral, and cardiometabolic variables. The longitudinal association between baseline HOMA-IR and the development of CVD was also explored. The longitudinal association between baseline HOMA-IR and the development of high urinary albumin-to-creatinine ratio was explored among nondiabetic participants (N = 1,401).

RESULTS

Cross-sectionally, HOMA-IR was associated with sex, residence location, smoking, and high-risk cardiometabolic profile. Prospectively, insulin resistance is associated with the development of CVD and decreased kidney function in this population.

CONCLUSIONS

Insulin resistance may have an important role in the pathogenesis of CVD and chronic kidney disease. Since obesity contributes to the development of insulin resistance, intervention focusing on modifiable factors such as physical activity and weight control may reduce the development of these diseases.Insulin resistance plays a major role in the development of type 2 diabetes (1,2). It has been reported as an independent predictor of cardiovascular diseases (CVDs), hypertension, and dyslipidemia (3,4). It is also involved in the development of polycystic ovary syndrome (5), nonalcoholic fatty liver disease (6), and certain types of cancer (7,8). The list of clinical conditions associated with insulin resistance/compensatory hyperinsulinemia is expanding. With the increasing prevalence of insulin resistance in the American population (9), increased future burdens of associated clinical conditions are predicted.The American Indian population has high prevalence of insulin resistance, especially among the younger age-groups compared with the general U.S. population (10) (at ages 45–49 years metabolic syndrome 44 and 57% among Strong Heart Study [SHS] men and women, respectively, vs. 20 and 23% among all men and women in the Third National Health and Nutrition Examination Survey [NHANES III]). Understanding the clinical outcomes of insulin resistance in this unique population may assist in reducing the burden of insulin resistance and related diseases in all Americans.To the best of the authors’ knowledge, there are few reports about the prospective association of insulin resistance and the development of kidney dysfunction. Also, the role of insulin resistance per se in the development of CVD is less clear. Specifically, this analysis will study 1) prospective associations between insulin resistance quantified by homeostasis model assessment (HOMA-IR) and incident CVD events and 2) prospective association between insulin resistance and decreased kidney function measured by increased urinary albumin-to-creatinine ratio (UACR).     

Impact of a psycho-oncological rehabilitation intervention on psychological distress: the experience of CeRiOn (Oncological Rehabilitation Centre) Florence 2007–2010

Background

Combining medical and psychological knowledge and accompanying patients in an individualised path, the Oncological Rehabilitation Centre of Florence (CeRiOn) aims at offering effective integrated rehabilitation interventions and at reducing psychological distress in cancer patients. In the present observational study, we measured the psychological distress at baseline and at the end of the completed rehabilitation processes.

Methods

A total number of 627 cancer patients were treated by the psycho-oncological service at CeRiOn in 2007–2010. Among them, 99 (all women) participated in more than or equal to three sessions, were followed up for clinical and life status for at least 1 year and had a formal conclusion of their psychological rehabilitation process. For 98 cases, both a baseline and a follow-up measure of distress, by the Psychological Distress Inventory (PDI) and the Distress Thermometer (DT), were available.

Results

Relevant before–after amelioration in this selected group of psychologically, highly suffering cancer patients has been shown. Almost all the patients (except 20 %) received both group and individual psychological support. The average rehabilitation process lasted 1.7 years. Average distress evaluation decreased from a baseline of 34.7 to 26.4 (P?<?0.001) according to PDI and from 5.9 to 2.2 according to DT (P?<?0.001).

Conclusions

On average, quite a long psychological support time was necessary to complete the rehabilitation process. During this period, patients who had a formal conclusion of the psychological support received at CeRiOn showed a significant reduction of their distress.     

Prognostic implications of microRNA-21 overexpression in pancreatic ductal adenocarcinoma: an international multicenter study of 686 patients

Despite progress in genomic characterization, no single prognostic marker that can be evaluated using an easy-to-perform and relatively inexpensive method is available for pancreatic ductal adenocarcinoma (PDAC). MicroRNAs, which are stable, tumor- and tissue-specific molecules, are potentially ideal biomarkers, and we established an inter-laboratory validated method to investigate miR-21 as a prognostic biomarker in PDAC. The study samples of PDAC patients were recruited from a test cohort of Glasgow (n = 189) and three validation cohorts of Pisa (n = 69), Sydney (n = 249), and International Cancer Genome Consortium (ICGC) (n = 249). Tissue microarrays were used for miR-21 staining by chromogenic in situ hybridization (CISH). The patients were subdivided into no/low and high miR-21 staining groups using a specific histoscore. Furthermore, miR-21 staining was evaluated against clinicopathological variables and follow-up data by Fisher/log-rank test and Cox proportional models. The prognostic variables found to be significant in univariate analysis (P value < 0.10) were included in multivariate analysis in a backward-stepwise fashion. MiR-21 expression was cytoplasmic, with more consistent staining in the malignant ductal epithelium than in the stroma. The expression of miR-21 was significantly associated with tumor size and lymph node metastasis, whereas no association was observed with other clinicopathological variables. High miR-21 staining (histoscore ≥ 45 [median score]) was an independent predictor of survival in the Glasgow test cohort (HR 2.37, 95% CI: 1.42-3.96, P < 0.0001) and three validation cohorts (Pisa, HR 2.03, 95% CI: 1.21-3.39, P = 0.007; Sydney, HR 2.58, 95% CI (1.21-3.39), P < 0.0001; and ICGC, HR 3.34, 95% CI: 2.07-5.84, P = 0.002) when adjusted for clinical variables in a multivariate model. In comparison to the patients with low miR-21, the patients with high miR-21 expression had significant increase in OS as they benefit from gemcitabine-based adjuvant chemotherapy (Glasgow 16.5 months [with chemotherapy] vs 10.5 months [without chemotherapy]); Sydney 25.0 vs 10.6; ICGC 25.2 vs 11.9. These results indicated that miR-21 is a predictor of survival, prompting prospective trials. Evaluation of miR-21 offers new opportunities for the stratification of patients with PDAC and might facilitate the implementation of clinical management and therapeutic interventions for this devastating disease.     

Dietary Patterns,Dietary Interventions,and Mammographic Breast Density: A Systematic Literature Review

Background: Breast cancer (BC) is the most common and deadliest malignancy among women. High mammographic breast density (MBD) is an established modifiable risk marker for BC, and it is of interest, for prevention purposes, to consider lifestyle factors that may modulate both MBD and BC risk. Here, we conducted a systematic review of the most up-to-date evidence on the association between diet as a whole and MBD. Methods: We considered as eligible for inclusion in our review (PROSPERO registration code CRD42022335289) the studies published until 31 December 2021, that reported on the association between a priori or a posteriori dietary patterns (in observational studies) or dietary interventions (in randomized controlled trials) and MBD. Results: In total, twelve studies were included. MBD tended to be inversely associated with adherence to dietary patterns characterized by high consumption of plant-based foods and low in meat, animal fats, and alcohol, defined both a priori (e.g., Mediterranean diet and WCRF/AICR guidelines) or a posteriori (e.g., “fruit-vegetable-cereal” and “salad-sauce-pasta/grains” patterns). Findings from intervention studies were in fair agreement with those from observational studies. Conclusions: While further studies are needed, we found suggestive evidence that the adoption of a healthy diet is associated with lower MBD.     

Uncommon causes of nerve compression in the distal forearm

IntroductionNerve compression by anomalous masses located at the wrist and distal forearm is an infrequent condition. They may compress underlying structures in the carpal tunnel region, causing pain and paresthesias, which leads to the wrong diagnosis of carpal tunnel syndrome.Clinical casesWe present three cases of patients with symptomatology and clinical tests compatible with compression of the median nerve in the carpal tunnel but whose physical examination showed a soft mass in the distal region of the forearm which was compressing the median nerve, as demonstrated by ultrasound evaluation.DiscussionThe reported cases of accessory muscles or lipomas described in the literature as causes of median nerve compression clinic are mainly described only after the surgical decompression of the carpal tunnel, due to the maintenance of residual symptoms.ConclusionCareful examination with an ultrasound evaluation prior to surgery may help to identify these cases and help planning surgical treatment.     

Videolaparoscopic microwave ablation in patients with HCC at a European high-volume center: Results of 815 procedures

Background: Videolaparoscopic (VL) microwave ablation (MWA) is not included in most of the international guidelines as a therapeutic option for hepatocellular carcinoma (HCC). Aim of this study was to assess the safety of VL MWA in patients with HCC for whom resection or percutaneous ablation is unsuitable. Methods: A retrospective analysis was performed on a prospective database of patients with HCC treated with VL MWA at our institution from 2009 to 2016. Patient demographics, operational characteristics, and complications were recorded. Statistical analysis was performed to identify safety profile, overall survival and recurrence rate. Results: A total of 815 VL MWA were performed in 674 patients with a mean age of 64 years. Patients had a mean Model for End-stage Liver Disease score of 10 (±3); 32.8% were Child B, 44.1% Barcelona Clinic Liver Cancer B-C. Perioperative mortality was 0.4%. Overall morbidity was 30.8%, with Dindo-Clavien complications ≥3 in 2%. The median length of stay was 2 days. In 43.1% VL MWA was the first-line therapy. Overall 1-, 3-, and 5-year survival rates were 81.9%, 54.9%, and 35.9%. Conclusions: The present is the largest series of VL ablation and the bigger number of patients with HCC treated with MW reported nowadays. It confirms the safety of a minimally invasive procedure for patients with HCC when resection or percutaneous ablation is not feasible.