Israel Medical Association Journal

Background: Several studies have shown that patients with fibromyalgia present with neuroendocrine, inflammatory, and coagulation features linked to cardiovascular disease development. However, the exact profile of cardiovascular risk factors and events in fibromyalgia remains to be defined.

Objectives: To compare the profile of cardiovascular risk factors and events between fibromyalgia outpatients and the general population in Italy.

Methods: Cardiovascular risk factors and events in fibromyalgia females were collected using the criteria adopted in the CUORE Project.

Results: The study comprised 62 female fibromyalgia patients and 4093 female controls from 35 to 75 years of age. The prevalence of hypertension, diabetes, atrial fibrillation, transient ischemic attack, and cardiovascular total burden was significantly higher in fibromyalgia females than in the general Italian population. No difference was found in blood fasting glucose, triglycerides, total and fractionated cholesterol levels, body mass index, and metabolic syndrome (MetS). The MetS rate was underestimated for methodological aspects.

Conclusions: Fibromyalgia is associated with an increased cardiovascular burden, probably through a specific risk factor profile.

Fibromyalgia syndrome is a chronic widespread musculoskeletal pain syndrome primarily characterized by fatigue, sleep disturbances, and cognitive impairment. Its etiology remains elusive despite ongoing research and has multifactorial elements. It has been shown that traumatic events and neuro-inflammation, autoimmunity, and genetic factors contribute to the pathogenesis of fibromyalgia syndrome.

Recent evidence has pointed to a bi-directional link between cardiovascular disease, traditional cardiovascular risk factors, and metabolic syndrome (MetS), together with the presence of fibromyalgia [1].

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders. Acute cholangitis (AC) is a life-threatening illness.

Objective: To determine whether NAFLD is a risk factor for the severity of AC.

Methods: We retrospectively studied hospitalized patients with a diagnosis of AC over 5 years. Patients were divided into a NAFLD group and a non-NAFLD group. We compared the two groups with regard to demographic characteristics, co-morbidities, laboratory data, and severity of AC (including Charlson Comorbidity Index [CCI] and Tokyo Consensus meeting criteria).

Results: In all, 298 of 419 hospitalized patients diagnosed with AC met the inclusion criteria. Of these, 73/298 (24.5%) were in the NAFLD group. NAFLD group patients were younger and more likely to be diabetic and obese than the non-NAFLD group. Participants in the NAFLD presented with higher serum C-reactive protein and higher liver enzymes (P < 0.05, for each parameter) and with more events of organ dysfunction (P < 0.001) and bacteremia (P < 0.005). Regarding the severity of AC according to Tokyo Consensus, among the NAFLD group more patients presented with Grade II (39.7 vs. 33.3%, P < 0.001) and Grade III (23.3 vs. 18.3, P < 0.001) cholangitis. More Grade I cholangitis was found among the non-NAFLD group (48.4 vs. 37%, P < 0.001). Multivariate logistic regression analysis showed that NAFLD was independently associated with severe AC, Grade III (odds ratio 3.25, 95% confidence interval 1.65–6.45, P = 0.038).

Conclusions: NAFLD is an independent risk factor for the severity of AC.

Background: Lumbar spinal stenosis (LSS) is a narrowing of the lumbar canal causing lower back pain, gluteal pain, and neurogenic claudication. LSS has been associated with cardiovascular co-morbidities. Metabolic syndrome (MetS), a pro-inflammatory condition involving a cluster of risk factors for cardiovascular disease and diabetes, is increasingly prevalent worldwide.

Objectives: To evaluate the prevalence of MetS in patients with LSS, compared to age- and sex-matched healthy controls, and to explore potential associations between MetS and LSS-related clinical parameters and cardiovascular risk factors.

Methods: We conducted a cross-sectional study including 64 patients diagnosed as symptomatic LSS (NASS criteria) and 32 controls. MetS was diagnosed using the 2009 Harmonizing criteria adjusted for South Americans. Multivariate logistic regression was used to identify independent risk factors for MetS. The level of statistical significance was set at 5%.

Results: The prevalence of MetS was significantly higher in the LSS group than in the control group (76.6% vs. 31.3%; P < 0.001). LSS patients displayed greater waist circumference (P = 0.003), blood glucose levels (P = 0.009) and arterial pressure (P < 0.001) than controls. The variables with independent influence on MetS in the logistic regression model were: diabetes (P = 0.008), blood glucose (P = 0.004), and body mass index (P = 0.005).

Conclusions: MetS was significantly more prevalent among LSS patients, and diabetes and elevated body mass index were found to be risk factors for MetS in these LSS patients

Background: Mean platelet volume (MPV), an essential component of the complete blood count (CBC) indices, is underutilized in common practice. In recent years, MPV has drawn strong interest, especially in clinical research. During inflammation, the MPV has a higher value because of platelet activation.

Objectives: To verify whether high MPV values discovered incidentally in healthy naïve patients indicates the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes.

Methods: A cohort study was used to assess the diagnostic value of high MPV discovered incidentally, in naïve patients (without any known cause of an abnormal high MPV, greater than  upper limit of the normal range, such as active cardiovascular diseases and metabolic syndrome).

Results: The mean MPV value in the patient group was 12.3 femtoliter. There was a higher incidence of metabolic syndrome in our research group than in the general population and a non-significant tendency of pre-diabetes. Family doctors more frequently meet naïve patients with high MPV than a hospital doctor. The results of our study are more relevant for him, who should know the relevance of such a finding and search for a hidden pre-diabetes or metabolic syndrome.

Conclusions: High MPV values discovered incidentally in healthy naïve subjects suggest the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes. No statistically significant association was found between MPV and the presence of cardiovascular disease

Background: Non-alcoholic fatty liver disease (NAFLD) is emerging as an important public health condition. The effect of Ramadan fasting on several metabolic conditions has been previously assessed.

Objectives: To assess the impact of Ramadan fasting on non-alcoholic steatohepatitis (NASH) severity scores.

Methods: A retrospective, case control study was conducted in Nazareth Hospital between 2017 and 2019. We included NAFLD patients who had been diagnosed by abdominal ultrasonography. The study population was divided in two matched groups: NASH subjects who fasted all of Ramadan and NAFLD/NASH subjects who did not fast (control). Metabolic/NASH severity scores, homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR), NAFLD Fibrosis Score (NFS), BARD scores, and fibrosis-4 (FIB4) scores were assessed in both groups before and after the Ramadan month.

Results: The study included 155 NASH subjects, 74 who fasted and 81 who did not. Among the fasting group, body mass index decreased from 36.7 ± 7.1 to 34.5 ± 6.8 after fasting (P < 0.003), NFS declined from 0.45 ± 0.25 to 0.23 ± 0.21 (P < 0.005), BARD scores declined from 2.3 ± 0.98 to 1.6 ± 1.01 (P < 0.005), and FIB4 scores declined from 1.93 ± 0.76 to 1.34 ± 0.871 (P < 0.005). C-reactive protein decreased from 14.2 ± 7.1 to 7.18 ± 6.45 (P < 0.005). Moreover, HOMA-IR improved from 2.92 ± 1.22 to 2.15 ± 1.13 (P < 0.005).

Conclusions: Ramadan fasting improved on inflammatory markers, insulin sensitivity, and noninvasive measures for NASH severity assessment.

Background: Recently, studies have found that non-alcholic fatty liver disease (NAFLD) is associated with bacterial infections. Attempts to identify risk factors for recurrent urinary tract infections (rUTIs) are still underway.

Objectives: To examine a possible association between NAFLD and rUTIs among premenopausal women.

Methods: In a case-control study, 1009 hospitalized premenopausal women with a UTI during a period of 3 years were retrospectively studied. A total of 186 subjects with rUTIs and 186 controls without a history of rUTIs were included in this study. Each participant had an abdominal ultrasonogram as part of the inclusion criteria. The two groups were compared in terms of risk factors for rUTIs, such as maternal history of rUTIs, use of contraceptives, frequency of sexual intercourse, metabolic syndrome, obesity, use of probiotics, serum levels of vitamin D, and NAFLD. An rUTI was defined as three or more episodes of UTI over a period of 1 year. NAFLD was diagnosed based on abdominal ultrasonography examination.

Results: Mean age of the 372 participants was 39.7 ± 5 years. NAFLD was diagnosed in 81/186 subjects (43.5%) with rUTIs vs. 40/186 controls (21.5%), P = 0.05. Women with rUTIs were more often obese and presented with lower serum levels of vitamin D than controls. Multivariate analysis showed that NAFLD (odds ratio = 1.6, 95% confidence interval 1.3–2.0, P = 0.04) were associated with rUTIs in premenopausal women.

Conclusions: NAFLD was associated with rUTI in premenopausal women, independent of metabolic syndrome. Further studies are needed to confirm this association.

Starvation in early life can lead to premature metabolic syndrome and bone demineralization. Osteoporosis in the Jewish population may not yet be a recognized syndrome, but the harsh conditions to which Holocaust survivors were exposed may have increased the incidence of the condition. Immigrants and refugees who came to Israel from East Africa and Yemen – whether decades ago or more recently – may have been at increased risk of under-nutrition during pregnancy, affecting both the mother and consequently the offspring. This malnutrition may be further exacerbated by rapid overfeeding in the adopted developed country. This problem was also recognized at the turn of the 21st century in poor and underdeveloped countries and is becoming a global public health issue. In this review, the risks for premature metabolic syndrome and bone demineralization are enumerated and preventive measures outlined. 

Background: Hyperplastic polyps (HPs) of the colon are the most common colorectal polyps. Metabolic syndrome components such as obesity and hyperlipidemia are considered the most common etiological factors for HPs as well contributing to the pathogenesis of fatty liver disease. Objectives: To determine the possible association between biopsy-proven steatohepatitis and hyperplastic colonic polyps. 

Methods: This retrospective cohort observational study conducted at the Holy Family Hospital in Nazareth, Israel, included subjects who underwent screening colonoscopy over a 2 year period. Data were extracted from the patient charts and included demographics, anthropometric measurements, vital signs, underlying diseases, medical therapy, laboratory data, and results of the liver biopsy. The colonoscopy report and pathological report of each extracted polyp were also evaluated.

Results: A total of 223 patients were included in the study: 123 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) and 100 patients without NASH who served as the control. Fourteen colonic adenomas (11% of patients) were found in the NASH group vs. 16 (16%) in the control group (P = 0.9); 28 HPs were found in the NASH group (22.7%) vs. 8 in the control group (8%) (P < 0.05). The multivariate analysis, after adjusting for, age, C-reactive protein and smoking, showed that the presence of NASH (OR 1.69, 95%CI 1.36–1.98, P < 0.01) was associated with increased risk for HP. 

Conclusions: Our study found an association between biopsy-proven steatohepatitis and the burden of hyperplastic polyp.

 

Background: There is a striking increase in the number of people with metabolic syndrome (MetS) as a result of the global epidemic of obesity and diabetes. Increasing evidence suggests that uric acid may play a role in MetS.

Objectives: To assess the prevalence of MetS in a large cohort from Israel and its association with hyperuricemia using the latest three definitions of MetS.

Methods: We conducted a retrospective analysis of the database from a screening center in Israel, using the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the International Diabetes Federation (IDF) and the Harmonizing definitions of MetS, to assess 12,036 subjects with an age range of 20–80 years.

Results: The mean age of the study sample was 46.1 ± 10.2 years and 69.8% were male. The prevalence of MetS was 10.6%, 18.2% and 20.2% in the revised NCEP ATP III, the IDF and the Harmonizing definitions respectively. The prevalence of hyperuricemia in subjects with MetS, for all three MetS definitions, was similar: 20.0%, 19.9% and 19.1% respectively. There was a graded increase in the prevalence of MetS among subjects with increasing levels of uric acid. The increasing trend persisted after stratifying for age and gender and after multivariate analysis (P for trend < 0.001).

Conclusions: This large cohort shows a high prevalence of MetS in Israel, but is still lower than the prevalence in western countries. Hyperuricemia is common in those subjects and might be considered a potential clinical parameter in the definition of MetS.
 

Objectives: To assess the risk of microvascular complications associated with the metabolic syndrome in diabetes subjects.

Methods: The study group comprised 415 diabetic subjects attending a primary care clinic. The prevalence of microvascular complications was compared between 270 diabetic subjects with metabolic syndrome (NCEP-III criteria) and 145 diabetic patients without.

Results: We found that as a group, diabetic subjects with metabolic syndrome had significantly higher frequency of microvascular-related complications than diabetic subjects without the syndrome (46.6% and 26.8% respectively, P = 0.0005). These include microalbuminuria (41.5% vs. 23.9%, P = 0.013), neuropathy (10.4% vs. 7.5%, P = 0.38), retinopathy (9.6% vs. 4.1%, P = 0.046) and leg ulcers (7.9% vs. 2.8%, P = 0.044). After adjustment for age, gender, glycemic control, disease duration, lipid profile and blood pressure, metabolic syndrome was associated with a significantly higher risk of microvascular complications: odds ratio (95% confidence interval) for nephropathy 2.27 (1.53–3.34), neuropathy 1.77 (0.79–4.0), retinopathy 3.42 (1.2–9.87), and leg ulcers 3.57 (1.08–11.95).

Conclusions: In addition to hyperglycemia and disease duration, the metabolic syndrome is a significant risk factor for the development of microvascular complications in diabetic subjects.

Objectives: To assess the prevalence of metabolic syndrome and different glucose intolerance states in healthy, overweight Arab individuals attending a primary healthcare clinic in Israel.

Methods: We randomly recruited 95 subjects attending a primary healthcare clinic who were healthy, overweight (body mass index >27) and above the age of 40. Medical and family history was obtained and anthropometric parameters measured. Blood chemistry and oral glucose tolerance test were performed after overnight fasting.

Results: Twenty-seven percent of the subjects tested had undiagnosed type 2 diabetes according to WHO criteria, 42% had impaired fasting glucose and/or impaired glucose tolerance and only 31% had a normal OGTT[1]. Metabolic syndrome was found in 48% according to criteria of the U.S. National Cholesterol Education Program, with direct correlation of this condition with BMI[2] and insulin resistance calculated by homeostasis model assessment. Subjects with metabolic syndrome had a higher risk for abnormality in glucose metabolism, and the more metabolic syndrome components the subject had the higher was the risk for abnormal glucose metabolism. Metabolic syndrome predicted the result of OGTT with 0.67 sensitivity and 0.78 specificity. When combined with IFG[3], sensitivity was 0.83 and specificity 0.86 for predicting the OGTT result.

Conclusions: According to our initial evaluation approximately 70% of the overweight Arab population in Israel has either metabolic syndrome or abnormal glucose metabolism, indicating that they are at high risk to develop type 2 diabetes and cardiovascular morbidity and mortality. This population is likely to benefit from an intervention program.

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[1] OGTT = oral glucose tolerance test

[2] BMI = body mass index

[3] IFG = impaired fasting glucose