Re-evaluating Methods for Assessing Differences in Response in Ileal vs. Colonic Crohn's Disease: A Post-hoc Analysis of the FITZROY Trial.

BACKGROUND AND AIMS: The ileum is the most commonly affected segment of the gastrointestinal tract in Crohn's disease (CD). We aimed to determine whether disease location affects response to filgotinib, a Janus kinase (JAK) inhibitor, in patients with moderate-to-severely active Crohn's disease (CD) and applying appropriate methods to account for differences in measuring disease activity in the ileum compared to the colon. METHODS: This post-hoc analysis of data from the FITZROY phase 2 trial (NCT02048618) compared changes in the Crohn's Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn's Disease (SES-CD) amongst patients with ileal-dominant and isolated colonic CD treated with 10 weeks of filgotinib 200 mg daily or placebo. A mixed effects model for repeated measures was used to test whether ileal disease responded differently than colonic disease, by evaluating for effect modification using the interaction term of treatment assignment-by-disease location. RESULTS: Numerically greater proportions of patients with isolated colonic disease compared to ileal-dominant CD achieved clinical remission (CDAI <150, 75.9% vs. 41.6%) and endoscopic response (SES-CD reduction by 50%, 52.5% vs. 15.5%) at Week 10. However, after adjusting for baseline disease activity by disease location and within-patient clustering effects, there was no significant difference in treatment response by disease location (mean difference in ΔCDAI between ileal-dominant vs. isolated colonic disease +9.24 [95% CI: -87.19, +105.67], p=0.85; mean difference in ΔSES-CD -1.93 [95% CI: -7.03, +3.44], p=0.48). CONCLUSIONS: Filgotinib demonstrated similar efficacy in ileal-dominant and isolated colonic CD when controlling for baseline disease activity and clustering effects.

Serum proteome signatures associated with ileal and colonic ulcers in Crohn's disease.

At a clinical level, ileal and colonic Crohn's disease (CD) are considered as separate entities. These subphenotypes need to be better supported by biological data to develop personalised medicine in CD. To this end, we combined different technologies (proximity extension assay, selected reaction monitoring, and high-sensitivity turbidimetric immunoassay (hsCRP)) to measure 207 immune-related serum proteins in CD patients presenting no endoscopic lesions (endoscopic remission) (n = 23), isolated ileal ulcers (n = 17), or isolated colonic ulcers (n = 16). We showed that isolated ileal ulcers and isolated colonic ulcers were specifically associated with 6 and 18 serum proteins, respectively: (high level: JUN, CNTNAP2; low level: FCRL6, LTA, CLEC4A, NTF4); (high level: hsCRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low level: CLEC3B, GSN, TNFSF12, TPSAB1). Isolated ileal ulcers and isolated colonic ulcers were detected by hsCRP with an area under the receiver operating characteristics curve of 0.64 (p-value = 0.07) and 0.77 (p-value = 0.001), respectively. We highlighted distinct serum proteome profiles associated with ileal and colonic ulcers in CD, this finding might support the development of therapeutics and biomarkers tailored to disease location. SIGNIFICANCE: Although ileal and colonic Crohn's disease present important clinical differences (eg, progression, response to treatment and reliability of biomarkers), these two entities are managed with the same therapeutic strategy. The biological specificities of ileal and colonic Crohn's disease need to be better characterised to develop more personalised approaches. The present study used robust technologies (selected reaction monitoring, proximity extension assays and turbidimetric immunoassay) to quantify precisely 207 serum immune-related proteins in three groups of Crohn's disease patients presenting: 1) no endoscopic lesions (endoscopic remission) (n = 23); 2) isolated ileal ulcers (n = 17); 3) isolated colonic ulcers (n = 16). We found distinct serum proteome signatures associated with ileal and colonic ulcers. Our findings could foster the development of biomarkers and treatments tailored to Crohn's disease location.

Fecal Calprotectin in Patients with Crohn's Disease: A Study Based on the History of Bowel Resection and Location of Disease.

Fecal calprotectin (FC) is commonly used to assess Crohn's disease (CD) activity. However, standardized cut-off values accounting for bowel resection history and disease location are lacking. In this study, we analyzed data from patients with CD who underwent magnetic resonance enterography, ileocolonoscopy, and FC measurements from January 2017 to December 2018. In 267 cases from 254 patients, the FC levels in the 'operated' patients were higher when the disease was active compared with those who were in the remission group (178 vs. 54.7 µg/g; p < 0.001), and similar findings were obtained for the 'non-operated' patients (449.5 vs. 40.95 µg/g; p < 0.001). The FC levels differed significantly according to the location of inflammation, with lower levels in the small bowel compared to those in the colon. The FC cut-off levels of 70.8 µg/g and 142.0 µg/g were considered optimal for predicting active disease for operated and non-operated patients, respectively. The corresponding FC cut-off levels of 70.8 µg/g and 65.0 µg/g were observed for patients with disease only in the small bowel. In conclusion, different FC cut-off values would be applicable to patients with CD based on their bowel resection history and disease location. Tight control with a lower FC target may benefit those with a history of bowel resection or small-bowel-only disease.

Efficacy of exclusive enteral nutrition on the mucosal healing of different gastrointestinal segments in children with Crohn's disease.

OBJECTIVE: To investigate the association between disease location and segmental mucosal healing (SMH) following exclusive enteral nutrition (EEN) in children with Crohn's disease (CD). METHODS: Treatment-naive pediatric patients with endoscopically active CD treated with EEN alone as induction therapy were retrospectively enrolled from January 1, 2017 to June 30, 2022. The simple endoscopic score for CD (SES-CD) was employed to score disease activity in the upper gastrointestinal (GI) tract (esophagus, stomach, duodenum), rectum, left colon, transverse colon, right colon, and terminal ileum. While the Lewis score assessed that of the small bowel from the jejunum to the proximal ileum (except the terminal ileum). The variation in the total scores for each segment and SES-CD subscores for each ileocolonic segment from baseline to 1 year after EEN therapy and the segmental endoscopic outcomes and potential predictors associated with SMH for the segments scored by SES-CD were evaluated. RESULTS: Overall, 82 children with CD were enrolled. Except for the upper GI segment, scores in other segments declined significantly from baseline to EEN completion (all P < 0.001). We analyzed 486 segments (79, 80, 81, 82, 82 and 82 from upper GI tract, terminal ileum, right colon, transverse colon, left colon, and rectum) and found that the segmental SES-CD at baseline (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.55-0.70, P < 0.001) and upper GI location (OR 0.25, 95% CI 0.11-0.55, P = 0.001) were associated with SMH at EEN completion. CONCLUSION: Disease location of the upper GI segment in pediatric CD was associated with SMH following EEN therapy.

IL-22BP production is heterogeneously distributed in Crohn's disease.

Crohn's disease (CD), a form of inflammatory bowel disease (IBD), is characterized by impaired epithelial barrier functions and dysregulated mucosal immune responses. IL-22 binding protein (IL-22BP) is a soluble inhibitor regulating IL-22 bioactivity, a cytokine proposed to play protective roles during CD. We and others have shown that IL-22BP is produced in IBD inflamed tissues, hence suggesting a role in CD. In this work, we extended the characterization of IL-22BP production and distribution in CD tissues by applying enzyme-linked immunosorbent assays to supernatants obtained from the culture of endoscopic biopsies of patients, and reverse transcription-quantitative polymerase chain reaction on sorted immune cell subsets. We reveal that IL-22BP levels are higher in inflamed ileums than colons. We observe that in a cell-intrinsic fashion, populations of mononuclear phagocytes and eosinophils express IL-22BP at the highest levels in comparison to other sources of T cells. We suggest the enrichment of intestinal eosinophils could explain higher IL-22BP levels in the ileum. In inflamed colon, we reveal the presence of increased IL-22/IL22BP ratios compared to controls, and a strong correlation between IL-22BP and CCL24. We identify monocyte-derived dendritic cells (moDC) as a cellular subtype co-expressing both cytokines and validate our finding using in vitro culture systems. We also show that retinoic acid induces the secretion of both IL-22BP and CCL24 by moDC. Finally, we report on higher IL-22BP levels in active smokers. In conclusion, our work provides new information relevant to therapeutic strategies modulating IL-22 bioactivity in CD, especially in the context of disease location.

[Consideration on the construction of acupuncture and moxibustion clinical diagnosis and treatment system with the core of "differentiation of disease location": taking "treatment" of Science of Acupuncture and Moxibustion as an example].

Based on the difference between disease and syndrome differentiation of acupuncture and moxibustion and each department of TCM, i.e. internal medicine, external medicine, gynecology and pediatrics, it is believed that "differentiation of disease location" is the key of disease and syndrome differentiation of acupuncture and moxibustion. According to the disease location, in the section "treatment" of Science of Acupuncture and Moxibustion, the disorders/illness are classified as zangfu disorder, disorders of limbs and meridians, dermatological disorder, ophthalmological and otorhinolaryngological disorder, gynecological disorder, as well as qi, blood and body fluid disorder. Besides, the rules of disease and syndrome differentiation, as well as treatment characteristics of each category are explained separately. It is considered that the clinical diagnosis and treatment system of acupuncture and moxibustion should be constructed by focusing on "differentiation of disease location".

Serum Analyte Profiles Associated With Crohn's Disease and Disease Location.

BACKGROUND: Crohn's disease (CD) can affect any segment of the digestive tract but is most often localized in the ileal, ileocolonic, and colorectal regions of the intestines. It is believed that the chronic inflammation in CD is a result of an imbalance between the epithelial barrier, the immune system, and the intestinal microbiota. The aim of the study was to identify circulating markers associated with CD and/or disease location in CD patients. METHODS: We tested 49 cytokines, chemokines, and growth factors in serum samples from 300 patients with CD and 300 controls. After quality control, analyte levels were tested for association with CD and disease location. RESULTS: We identified 13 analytes that were higher in CD patients relative to healthy controls and that remained significant after conservative Bonferroni correction (P < 0.0015). In particular, CXCL9, CXCL1, and interleukin IL-6 had the greatest effect and were highly significant (P < 5 × 10-7). We also identified 9 analytes that were associated with disease location, with VEGF, IL-12p70, and IL-6 being elevated in patients with colorectal disease (P < 3 × 10-4). CONCLUSIONS: Multiple serum analytes are elevated in CD. These implicate the involvement of multiple cell types from the immune, epithelial, and endothelial systems, suggesting that circulating analytes reflect the inflammatory processes that are ongoing within the gut. Moreover, the identification of distinct profiles according to disease location supports the existence of a biological difference between ileal and colonic CD, consistent with previous genetic and clinical observations.

Meta-Analysis of IBD Gut Samples Gene Expression Identifies Specific Markers of Ileal and Colonic Diseases.

BACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by chronic inflammation and tissue damages in limited segments of the digestive tract. Pathogenesis in the tissue and mucosal inflammation probably differs according to disease location. Our aim was to further analyze transcriptomic profiles in different locations of IBD, differentiating ulcerative colitis (UC), colonic Crohn's disease (CD), ileal CD, and pouchitis, with respect to normal colonic and ileal mucosa. We thus performed a meta-analysis focusing on specific transcriptomic signatures of ileal and colonic diseases. METHODS: We identified 5 cohorts with available transcriptomic data in ileal or colonic samples from active IBD and non-IBD control samples. The meta-analysis was performed on 1047 samples. In each cohort separately, we compared gene expression in CD ileitis and normal ileum; in CD colitis, UC, and normal colon; and finally in pouchitis and normal ileum. RESULTS: We identified specific markers of ileal (FOLH1, CA2) and colonic (REG3A) inflammation and showed that, with disease, some cells from the ileum start to express colonic markers. We confirmed by immunohistochemistry that these markers were specifically present in ileal or colonic diseases. We highlighted that, overall, colonic CD resembles UC and is distinct from ileal CD, which is in turn closer to pouchitis. CONCLUSIONS: We demonstrated that ileal and colonic diseases exhibit specific signatures, independent of their initial clinical classification. This supports molecular, rather than clinical, disease stratification, and may be used to design drugs specifically targeting ileal or colonic diseases.

We perform a meta-analysis of publicly available inflammatory bowel disease transcriptomes and identify FOLH1, REG3A, and CA2 as specific markers of ileal and colonic diseases. We demonstrate that Crohn's colitis resembles ulcerative colitis, while Crohn's ileitis resembles pouchitis.

Consideration on the construction of acupuncture and moxibustion clinical diagnosis and treatment system with the core of "differentiation of disease location": taking "treatment" of Science of Acupuncture and Moxibustion as an example / 中国针灸

Based on the difference between disease and syndrome differentiation of acupuncture and moxibustion and each department of TCM, i.e. internal medicine, external medicine, gynecology and pediatrics, it is believed that "differentiation of disease location" is the key of disease and syndrome differentiation of acupuncture and moxibustion. According to the disease location, in the section "treatment" of Science of Acupuncture and Moxibustion, the disorders/illness are classified as zangfu disorder, disorders of limbs and meridians, dermatological disorder, ophthalmological and otorhinolaryngological disorder, gynecological disorder, as well as qi, blood and body fluid disorder. Besides, the rules of disease and syndrome differentiation, as well as treatment characteristics of each category are explained separately. It is considered that the clinical diagnosis and treatment system of acupuncture and moxibustion should be constructed by focusing on "differentiation of disease location".

Alterations in Gut Microbial Communities Across Anatomical Locations in Inflammatory Bowel Diseases.

We previously discovered that gut microbiota can serve as universal microbial biomarkers for diagnosis, disease activity assessment, and predicting the response to infliximab treatment for inflammatory bowel diseases (IBD). Much still remains unknown about the relationship between alterations in gut microbiota and IBD affected bowel region, in particular in the case of ulcerative colitis (UC) and colonic Crohn's disease (cCD) without endoscopic and biopsy data. In the current study gut microbiota from a population in China was found to be distinct from that of the Western world [Human Microbiome Project (HMP) data]. Furthermore, both gut microbiota greatly differed from microbiota of other anatomical locations (oral, skin, airway, and vagina), with higher alpha-diversity (Chinese gut > HMP gut > oral microbiome > airway microbiome > skin microbiome > vaginal microbiome), and marked differences in microbiome composition. In patients with IBD in China, UC was characterized by the presence of Gardnerella, while cCD was characterized by the presence of Fusobacterium. Moreover, gut microbiota, such as Gardnerella and Fusobacterium, may be potential biomarkers for identifying UC from cCD. Together, this study revealed crucial differences in microbial communities across anatomical locations, and demonstrated that there was an important association between IBD affected bowel region and gut microbiota.

Circulating microRNA profiles in different arterial territories of stable atherosclerotic disease: a systematic review.

AIMS: Atherosclerosis is associated with altered circulating microRNA profiles. It is yet unclear whether the expression of these potential biomarkers differs according to the location of atherosclerosis. We assessed whether atherosclerosis of different arterial territories, except the coronary, is associated with specific circulating microRNA profiles. METHODS: A systematic search in PubMed, Web of Science, Embase, and Cochrane Library was carried out using a retrieval strategy including MESH and non-MSH terms. Eligible studies have compared circulating microRNA profiles between individuals with and without stable atherosclerotic disease of large or medium size arteries. The review protocol was registered in PROSPERO database (reference CRD42017073846). RESULTS: Eighteen studies were selected for qualitative synthesis: ten focused on carotid, six on lower limbs, and two on renal arteries atherosclerosis, none reporting on other locations. A common microRNA profile to different atherosclerotic disease locations was identified, including deregulation of miR-21, miR-30, miR-126, and miR-221-3p. Specific microRNA profiles for each territory were also identified, with consistency across studies, such as deregulation of miR-21 and miR-29 in carotid atherosclerosis, and let 7e, miR-27b, miR-130a, and miR-210 in lower limbs atherosclerosis. The robustness of the results was very high for let 7e, miR-29, miR-30, considering both the adjustment of microRNA expression for baseline variables and the replication of results in different studies (miR-29 in carotid, let 7e in lower limbs, and miR-30 in carotid and lower limbs atherosclerosis). Globally, the deregulated microRNAs are associated with control of angiogenesis, endothelial cell function, inflammation, cholesterol metabolism, oxidative stress and extracellular matrix composition. CONCLUSIONS: A common microRNA profile to different atherosclerotic disease locations and specific microRNA profiles for each territory were identified. These findings may provide insights into pathophysiology and be useful for selecting potential biomarkers for clinical practice. To the best of our knowledge, no systematic data on this subject has been reported.

[Professor ZHAO Jiping's thoughts and methods of penetration needling].

As a vital part of acupuncture and moxibustion,the theory of penetration needling obviously lags behind the practice. This article summarizes the thoughts andmethods of penetration needling by professor ZHAO Jiping. Based on the three basic elements of penetrating acupuncture, including the acupoint, needle and manipulation, the academic origins, the application of penetrating acupuncture at present and the clinical cases are reviewed; the essential content and the extension meaning of needle penetration are summarized, which is based on the identification of the location, pathology and characteristics of disease, combined with the characteristics of acupoints and the tissue structure of the part, we quantify the intensity of stimulation, so as to provide featured reference clinical practice.

Analysis on Some Problems of Taiyang Disease and Blood Storage Syndrome / 浙江中医药大学学报

[Objective] To explore the location and pathogenesis of Taiyang disease and blood storage syndrome. [Method]This article starts from the controversy about the position of Taiyang disease and blood storage syndrome of the past dynasties,analyzing and defining 4 related problems layer by layer,and expounding the position, etiology, pathogenesis and other problems of Taiyang disease and blood storage syndrome. [Results]Firstly, "urine self benefit" means that the Taiyang disease and blood storage syndrome is not located in the bladder,it is wrong idea that typhoid scholar considers the idea of "blood storage bladder";Secondly, "bleeding" does not mean bleeding in the urine, mainly refers to blood stasis from feces,also referred to bleeding caused by female cytoplasmic disease; Thirdly, the "hot knot bladder" does not refer to the bowels of the bladder, it refers to that lower focal low abdominal position;Fourthly, "hot knot bladder" and "hot in the lower coke" have the same connotation,the emphasis is on explaining the etiology and pathogenesis of Taiyang disease and blood storage syndrome, that being the surface evil of Taiyang typhoid disease is not relieved, evil heat progressing into the small intestine,or liver(Jueyin) and uterus,blood stasis and heat poison intersecting in the lower focal and lower abdomen;Fifthly, the specific location of hypofocal disease in the small intestine or uterus and other abdominal parts.[Conclusion]The position of Taiyang disease and blood storage syndrome is not in the bladder, but in the lower abdomen.The etiology and pathogenesis is that the surface evil of Taiyang typhoid disease is not relieved, evil heat progressing into the small intestine,or liver(Jueyin) and uterus,blood stasis and heat poison intersecting in the lower focal and lower abdomen.

Professor 's thoughts and methods of penetration needling / 中国针灸

As a vital part of acupuncture and moxibustion,the theory of penetration needling obviously lags behind the practice. This article summarizes the thoughts andmethods of penetration needling by professor . Based on the three basic elements of penetrating acupuncture, including the acupoint, needle and manipulation, the academic origins, the application of penetrating acupuncture at present and the clinical cases are reviewed; the essential content and the extension meaning of needle penetration are summarized, which is based on the identification of the location, pathology and characteristics of disease, combined with the characteristics of acupoints and the tissue structure of the part, we quantify the intensity of stimulation, so as to provide featured reference clinical practice.

[Discussion on the acupuncture and moxibustion thoughts of diagnosis and treatment for secondary dysmenorrhea of adenomyosis on the basis of disease location and pathogenesis].

To discuss the acupuncture and moxibustion thoughts of diagnosis and treatment for secondary dysmenorrhea of adenomyosis on the basis of disease location and pathogenesis. In clinic, we take the "principle, method, prescription, acupoint and technic" as the outline, paying attention to identify disease location and establishing the method of "promoting blood to remove stasis, regulating thoroughfare vessel and conception vessel" on the basis of the pathogenesis of "stasis obstructing uterus, disharmony of thoroughfare vessel and conception vessel". The prescription combines "dredging" with "conditioning", and the emphasis should be different in different periods. In menstrual period, we put emphasis on activating the circulation of qi and blood as well as clearing meridians to relieve pain and choose the acupoints on the spleen meridian of foot-taiyin and experimental points, such as Diji (SP 8), Sanyinjiao (SP 6), Ciliao (BL 32), Shiqizhui (EX-B 8). In the intermenstrual period, we regulate the qi and blood of thoroughfare vessel and conception vessel, and the function of viscera. The acupoints for the disease root are mainly at spleen meridian of foot-taiyin and conception vessel, such as Sanyinjiao (SP 6), Guanyuan (CV 4), Zigong (EX-CA 1), Zusanli (ST 36). And the reinforcing and reducing technic are applied accordingly.

Discussion on the acupuncture and moxibustion thoughts of diagnosis and treatment for secondary dysmenorrhea of adenomyosis on the basis of disease location and pathogenesis / 中国针灸

To discuss the acupuncture and moxibustion thoughts of diagnosis and treatment for secondary dysmenorrhea of adenomyosis on the basis of disease location and pathogenesis. In clinic, we take the "principle, method, prescription, acupoint and technic" as the outline, paying attention to identify disease location and establishing the method of "promoting blood to remove stasis, regulating thoroughfare vessel and conception vessel" on the basis of the pathogenesis of "stasis obstructing uterus, disharmony of thoroughfare vessel and conception vessel". The prescription combines "dredging" with "conditioning", and the emphasis should be different in different periods. In menstrual period, we put emphasis on activating the circulation ofand blood as well as clearing meridians to relieve pain and choose the acupoints on the spleen meridian of foot-and experimental points, such as Diji (SP 8), Sanyinjiao (SP 6), Ciliao (BL 32), Shiqizhui (EX-B 8). In the intermenstrual period, we regulate theand blood of thoroughfare vessel and conception vessel, and the function of viscera. The acupoints for the disease root are mainly at spleen meridian of foot-and conception vessel, such as Sanyinjiao (SP 6), Guanyuan (CV 4), Zigong (EX-CA 1), Zusanli (ST 36). And the reinforcing and reducing technic are applied accordingly.

Analysis of Diagnosis on TCM Pathogenesis of Disorders of Depression with Metabolic Sydrome from TCM Psychosoma Theory / 浙江中医药大学学报

[Objective]This paper will pitch-in TCM psychosomatic theory(from Huangdi Neijing),exploring the disorders of depression with the metabolic syndrome and pathogenesis of traditional Chinese medicine,so as to provide effective ideas for the treatment of depression with metabolic syndrome.[Methods]:Through expansion on traditional chinese medicine's basic understanding of depression with metabolic syndrome,utilizing basic TCM viscera-state theory, from the causes of this disease,key factors,pathogenesis transformation three aspects to discuss the pathogenesis of the disease. [Results]By discussing the heart,liver,spleen function of zang-fu organs and their mutual relations in the role and impact of the disease development process, this paper thinks of the nature of disease as asthenia in origin and asthenia in superficiality,which locates in spleen,has association with heart and liver, phlegm, qi and blood stasis is the disease of pathological product of pathological factors to promote the development of the disease.Kidney would be involved in it with long course of disease.The therapy could focus on tonifying spleen,nourishing heart and soothing liver,with methods of promoting the circulation of qi,removing blood stasis and reducing phlegm,meanwhile looking out to protect kidney.[Conclusion]Disorder of depression and pathogenesis of TCM of metabolic syndrome,to guide the clinical treatment of the disease and the theory of traditional Chinese medicine development has practical significance.

Prevalence and risk of cardiovascular risk factors and events in offspring of patients at high vascular risk and effect of location of parental vascular disease.

BACKGROUND: Offspring of patients with cardiovascular disease are at increased risk of developing cardiovascular events. We evaluated whether prevalence of risk factors in offspring of patients with increased cardiovascular risk is higher compared with the general population and whether the risk of cardiovascular events and prevalence of cardiovascular risk factors in offspring is dependent on parental vascular disease location. METHODS: Of 4270 patients enrolled in the SMART cohort we assessed after a follow-up of 7 years (IQR 4-8) the presence of cardiovascular risk factors and disease in their 10,572 children by questionnaire. The SMART patients had symptomatic vascular disease (coronary artery disease (CAD) (n = 1826), cerebrovascular disease (CVD) (n = 637), peripheral artery disease (PAD) (n = 275), abdominal aortic aneurysm (AAA) (n = 98), polyvascular disease (≥ 2 vascular manifestations) (n = 371)) or risk factors (hypercholesterolemia, diabetes, hypertension) (n = 1063). The prevalence of risk factors in offspring was compared with the general population and stratified for parental vascular disease location. The relation between parental vascular disease location and cardiovascular events in offspring was determined by Poisson regression. RESULTS: The offspring had higher prevalence of in particular hypercholesterolemia and hypertension compared with the general population, irrespective of the parental vascular disease location. Higher risks of cardiovascular events compared with offspring of patients without manifest vascular disease were observed in offspring of patients with CAD (PR 1.8, 95%CI 0.9-3.4), CVD (PR 2.4, 95%CI 1.2-4.8), PAD (PR 2.8, 95%CI 1.3-6.4), polyvascular disease (PR 2.5, 95%CI 1.2-5.2), but not with AAA (PR 1.7, 95%CI 0.5-6.1). CONCLUSIONS: In offspring from patients with cardiovascular disease or risk factors, the prevalence of traditional risk factors was higher compared with the general population, independent of the location of vascular disease of the parent. Offspring of patients with PAD had the highest risk of developing vascular disease.

Parental history and the risk of subsequent vascular events in patients with clinically manifest vascular disease: the effects of sex of the parent and vascular disease location.

BACKGROUND: Parental history of cardiovascular disease is a risk factor for first vascular events. It is unknown whether this also holds for subsequent events in patients with vascular disease. Also, the role of the location of parental vascular disease and the sex of the affected parent is unidentified. METHODS: In a cohort of 4529 patients with symptomatic vascular disease enrolled in the Second Manifestations of Arterial Disease (SMART) Study, the relation between parental cardiovascular history under the age of sixty, sex of the parent, location of parental vascular disease (heart, brain, lower extremities) and subsequent myocardial infarction (MI), stroke, vascular death and peripheral artery disease (PAD) was determined by Cox-proportional hazard analyses. RESULTS: During a median follow-up of 4.9 years (interquartile range 2.5-7.0), MI was experienced by 220 patients, stroke by 112, PAD by 297, whereas 371 patients died. A positive parental history of cardiovascular disease, without knowledge of vascular disease location and sex of that particular parent, was not associated with subsequent events (HR1.0; 95%CI 0.8-1.3). For specific types of parental history regarding sex and vascular location, having a father with a history of PAD was related to an increased risk of incident PAD (HR3.1; 95%CI 2.1-4.6). CONCLUSIONS: A positive parental history of cardiovascular disease without information about vascular disease location and sex does not increase the risk of recurrent vascular events in patients with symptomatic vascular disease. Vascular patients with a father with PAD have an increased risk of subsequent peripheral artery disease compared with vascular patients without such a family history.