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1.
Article in English | MEDLINE | ID: mdl-32193201

ABSTRACT

OBJECTIVE: Familial combined hyperlipidemia (FCHL) is common among survivors of a premature myocardial infarction. FCHL patients are characterized by visceral obesity, fatty liver, and insulin resistance. The aim of the present study was to determine the incidence and determinants of type 2 diabetes (T2D) in a longitudinal cohort of FCHL pedigrees. RESEARCH DESIGN AND METHODS: FCHL patients, their unaffected relatives and spouses included in our baseline cohort in 1998-2005 (n=596) were re-invited to determine the incidence of self-reported T2D (that was confirmed by medical records), used as the primary outcome measure. The Fatty Liver Index (FLI) and Homeostasis Model Assessment Insulin Resistance (HOMA2-IR) were used as markers of fatty liver and insulin resistance, respectively. A subset of the original cohort underwent ultrasound of the liver, and subcutaneous and visceral fat in 2002-2005 (n=275; 'ultrasound subcohort'). RESULTS: Follow-up data (median: 15 years) was acquired for 76%. The incidence rate of T2D was significantly higher in FCHL patients compared with spouses (19.2 per 1000 person-years vs 2.8 per 1000 person-years; HR : 6.3, 95% CI: 2.4 to 16.8), whereas no differences were observed between unaffected relatives and spouses (HR: 0.9, 95% CI: 0.3 to 2.6). Cox's proportional hazard regression analyses showed that baseline HOMA2-IR and FLI≥60, but not waist circumference, BMI, or the FCHL affected state, were independently associated with incident T2D. Similar results were obtained in the ultrasound subcohort (median follow-up: 11 years), in which baseline HOMA2-IR and fatty liver (assessed by ultrasound) were independently associated with incident T2D. CONCLUSION: This study further corroborates the suggestion that the liver plays a central role in the pathogenesis of cardiometabolic complications in FCHL. It supports periodical screening for T2D in this high-risk population.


Subject(s)
Diabetes Mellitus, Type 2 , Fatty Liver , Hyperlipidemia, Familial Combined , Hyperlipidemias , Diabetes Mellitus, Type 2/epidemiology , Humans , Hyperlipidemia, Familial Combined/complications , Hyperlipidemia, Familial Combined/epidemiology , Incidence
2.
Atherosclerosis ; 280: 1-6, 2019 01.
Article in English | MEDLINE | ID: mdl-30448567

ABSTRACT

BACKGROUND AND AIMS: Familial combined hyperlipidemia (FCHL) is a complex dyslipidemia associated with premature cardiovascular disease (CVD). The present study was conducted to 1) determine the incidence of CVD in FCHL in this era of protocolled, primary prevention; and 2) examine whether cardiovascular risk estimation based on the Systemic Coronary Risk Estimation (SCORE) chart, as proposed in the 2016 ESC/EAS guidelines for the management of dyslipidemia, is justified in FCHL. METHODS: FCHL patients, their normolipidemic (NL) relatives and spouses originally included in our baseline cohort in 1998-2005 (n = 596) were invited for a follow-up visit to determine the incidence of CVD, defined as (non-)fatal coronary artery disease, ischemic stroke and peripheral artery disease requiring invasive treatment. RESULTS: Follow-up data (median: 15 years) was acquired for 85% of the original cohort. The cumulative incidence of CVD was significantly higher in FCHL patients than in spouses (23.6% versus 4.7%; hazard ratio (HR): 5.4, 95%CI: 2.0-14.6; HR after adjustment for risk factors included in SCORE: 4.7, 95%CI: 1.6-13.8), but not in NL relatives compared to spouses (5.8% versus 4.7%). The SCORE chart tended to overestimate CVD risk in the spouses (observed [O]/expected [E] ratio:0.2, p = 0.01), but not in FCHL patients (O/E:1.3, p = 0.50). CONCLUSIONS: Risk of primary CVD is still substantially increased in FCHL patients, despite preventive measures. The overestimation of CVD risk by the SCORE chart - a nowadays frequently observed phenomenon thanks to improved primary prevention - was not seen in FCHL. These results suggest that more aggressive treatment is justified to avoid excessive CVD in FCHL.


Subject(s)
Cardiovascular Diseases/complications , Hyperlipidemia, Familial Combined/complications , Adult , Aged , Brain Ischemia/complications , Brain Ischemia/epidemiology , Cardiovascular Diseases/epidemiology , Coronary Artery Disease/complications , Coronary Artery Disease/epidemiology , Female , Follow-Up Studies , Humans , Hyperlipidemia, Familial Combined/epidemiology , Incidence , Longitudinal Studies , Male , Middle Aged , Peripheral Arterial Disease/complications , Peripheral Arterial Disease/epidemiology , Proportional Hazards Models , Risk Assessment , Time Factors
3.
BMC Musculoskelet Disord ; 16: 68, 2015 Mar 24.
Article in English | MEDLINE | ID: mdl-25879958

ABSTRACT

BACKGROUND: In adult patients with developmental hip dysplasia, a surgical procedure (triple innominate osteotomy) of the pelvic bone can be performed to rotate the acetabulum in the frontal plane, establishing better acetabular coverage. Although common clinical hip scores demonstrate significant improvements after surgery, they provide only overall information about function. The purpose of this study was to quantify the long-term outcome of triple innominate osteotomy in more detail using gait analyses and muscle strength measurements. METHODS: We performed gait analyses at self-selected walking speed as well as isometric hip and knee muscle strength tests in twelve women who had undergone a unilateral triple innominate osteotomy (age: 34 ± 12 y, time post surgery: 80 ± 18 m). We compared the results to reference values obtained from eight healthy peers (age: 33 ± 10 y). RESULTS: The patients exhibited slight asymmetries in step length (smaller steps) and stance time (longer stance) as well as lower hip abduction moments in the operated limb in early stance compared to the non-operated limb. However, there were no differences in gait compared to healthy controls, even though the patients showed reduced bilateral hip abduction strength compared to controls. CONCLUSIONS: Our results indicate that the patients' gait pattern had generally recovered very well, despite slight asymmetries in spatiotemporal parameters. Subtle deviations in hip abduction moments were observed during gait, whereas hip abduction strength was substantially reduced. Hence, the patients walked at a higher percentage of their maximal capacity. They may, therefore, be prone to fatigue and adopt compensatory gait strategies more quickly than healthy peers when walking long distances.


Subject(s)
Gait/physiology , Hip Dislocation/surgery , Lower Extremity/physiology , Muscle Strength/physiology , Muscle, Skeletal/physiology , Osteotomy/methods , Pelvic Bones/surgery , Adult , Biomechanical Phenomena/physiology , Case-Control Studies , Female , Follow-Up Studies , Hip Joint/physiology , Hip Joint/surgery , Humans , Isometric Contraction/physiology , Middle Aged , Range of Motion, Articular/physiology , Treatment Outcome , Walking/physiology
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