Second-degree Relatives Of Patients Research Articles

Association of renal cell carcinoma and hematologic malignancy.

449 Background: An increased incidence of both RCC and HM occurring in the same patients has been reported. Also, a relationship between adenocarcinoma and HM has been previously suggested. Moreover, detailed family history in our patients with RCC suggested an increased incidence of HM in their family members. The purpose of this study is to characterize the HM in relatives of patients with RCC. Methods: Data from 700 patients with RCC seen by us from 2004 to the present were retrospectively evaluated through chart review. The patient, family history and pathology characteristics were collected to determine the frequency of HM in first and second-degree relatives of patients with RCC. Pedigrees were then constructed and subtypes of HM were characterized. Results: A family history of HM was observed in 74 relatives involving 59 families. Of these, 50/74 cases of HM were in first-degree relatives and 19/74 were in second-degree relatives. The most common HMs were lymphoma and leukemia: 24 non-Hodgkin’s lymphoma, 8 Hodgkin’s lymphoma, 8 lymphoma not further specified (NOS), 11 chronic lymphocytic leukemia, 1 chronic myeloid leukemia, 1 acute myeloid leukemia, 5 acute leukemia NOS and 4 leukemia NOS. Other HM observed were multiple myeloma in 2 patients, Waldenström’s macroglobulinemia, myelodysplastic syndrome, and myelofibrosis. Additionally, 2 relatives had blood cancers that were NOS. Of the 59 patients with RCC, 40 had clear cell histology, 4 papillary, 3 chromophobe, 1 sarcomatoid, 1 transitional and in 10, RCC histology was not recorded. Conclusions: HM is observed in patients with RCC with increased frequency compared with the SEER database. We now observed an increased frequency of HM in relatives of patients with RCC. The majority of HMs observed were B-cell malignancies, as we previously reported for HMs that occur in patients with breast cancer or RCC. The etiology of this association remains unclear, but suggests a common etiopathogenesis for RCC and B-cell tumors. Genetic mutations, hereditary immunological defects, and environmental factors may be involved. A larger study with statistical evaluation for confirmation is required. We plan to collect serum and tissue samples from patients and relatives for future molecular studies.

Familial rheumatoid arthritis in patients referred to rheumatology clinics of Tabriz, Iran

The familial clustering of rheumatoid arthritis (RA) in first and second degree relatives of patients supports the role of genetic factors. The proportion of heredity in its development is roughly 60%; however, most individuals closely related to someone with RA do not get the disease. Considering the lack of sufficient data on the familial aggregation of RA in Iran, we designed this study for clarifying the familial prevalence of RA. To determine the prevalence of RA among relatives of patients with RA and to evaluate the mean disease onset age in relatives. In a longitudinal study from July 2008 to July 2010, we followed 210 unrelated patients with RA and their first and second degree relatives (FDR+ and SDR+), by interviewing and physical examination of those with symptoms, to ascertain prevalence. Familial RA was defined by presence of at least two siblings fulfilling the 1987 ACR criteria for RA. We demonstrated that 17.6% of patients have at least one affected relative. The prevalence of RA in the family of studied patients was 0.83% (42 people). Thirty-two in FDR+ and 10 people in SDR+ (2.53% and 0.26% of all family), also 1.12% in female relatives and 0.39% in male relatives had RA. The odds ratio for FDR/SDR was 2.52. The mean age at disease onset in relatives was 42.30 ± 1.51 years in FDR+ and 34.40 ± 2.10 years in the SDR+ group (0.03). The risk of RA is greatest in FDR+ and is likely to be due to a combination of inherited and environmental factors.

Islet Autoantibody Seroconversion in the DPT-1 Study

OBJECTIVEAlthough type 1 diabetes autoimmunity frequently begins in childhood, little is known about the relationship between age and autoimmunity development. Our aim was to determine the timing of seroconversion to diabetes-associated autoantibody (DAA) positivity and risk in first- and second-degree relatives of patients with type 1 diabetes.RESEARCH DESIGN AND METHODSStudy subjects were identified through the Diabetes Prevention Trial-Type 1 (DPT-1). Children 3–18 years of age (n = 42,447) were screened for DAAs; 1,454 were ICA positive (≥10 JDF units), 1,758 were GAD65 positive, and 899 were ICA512 positive at the time of initial screening. Subjects who were initially antibody negative (n = 39,212) were recalled for rescreening, and 11,813 returned for rescreening.RESULTSDAA seroconversion occurred in 469 (4%) children; 258 seroconverted to ICA, 234 to GAD65, and 99 to ICA512. The median time to seroconversion was 2 years. The 2-year risk for DAAs was highest in early childhood. For each 1-year increase in age in this cohort, the risk of any autoantibody seroconversion (HR 0.95, 95% CI 0.92–0.97) decreased by 5%, and for any two autoantibodies risk decreased by 13% (0.87, 0.82–0.93).CONCLUSIONSRisk of autoantibody seroconversion among children followed in DPT-1 is age dependent. Younger children have the highest risk for DAAs, with the majority of children seroconverting by 13 years of age (75%). This suggests that annual screenings should be started in early childhood and continued through early adolescence to identify the majority of subjects at risk for type 1 diabetes and eligible for prevention trials.

Abstract CN09-04: Multiple behavior interventions among cancer survivors and their relatives

Abstract CN09-04: Multiple behavior interventions among cancer survivors and their relatives

Analysis of TACI mutations in CVID & RESPI patients who have inherited HLA B*44 or HLA*B8

BackgroundRecent reports have suggested that Common Variable Immunodeficieny (CVID) can present as an autosomal dominant trait dependent on the inheritance of a set of uncommon mutations/alleles of TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) involving exons 3 or 4. Penetrance, however, appears to be incomplete. Among our clinic population, the greatest genetic linkage for CVID is to the major histocompatibility complex (MHC) on chromosome 6. The majority of our patients have inherited HLA *DQ2, *DR7, *DR3(17), *B8, and/or *B44. Of these, HLA*B44 was present in almost half of the patients and was thus the most common susceptibility allele. HLA *B44 was also found to be over-represented among patients who presented to our clinic with adult-onset recurrent sinopulmonary infections (RESPI) and normal serum immunoglobulin levels, a cohort that included first and second degree relatives of patients with CVID. One of the two original reports of the association between TACI and CVID also reported Human Leukocyte Antigen (HLA) haplotypes. Of 13 affected subjects, nine had inherited HLA *B8 and six had inherited HLA B44. This raised the possibility that TACI mutations might synergize with MHC class I alleles to enhance susceptibility to humoral immune deficiency.MethodsWe identified 63 CVID patients irrespective of HLA status and 13 RESPI patients who had inherited HLA*B44. To evaluate for mutations in the gene for TACI, we PCR amplified and sequenced TACI exons 3 and 4 from these patients.ResultsOf the 76 patients, eleven proved heterozygous for a previously reported, silent T->G polymorphism [rs35062843] at proline 97 in exon 3. However, none of the 13 RESPI patients and only one of the 63 CVID patients inherited a TACI allele previously associated with CVID. This patient was heterozygous for the TACI A181E allele (exon 4). She did not carry *DQ2, *DR7, *DR3(17), *B8, or *B44.ConclusionThese findings suggest that TACI mutations are unlikely to play a critical role in creating susceptibility to CVID among patients with previously recognized MHC class I and class II susceptibility alleles.Supported by NIH/USIDNET N01-AI30070, NIH R21 AI079741 and NIH M01-RR00032

Epidemiological features of Turkish patients with sarcoidosis

Epidemiological characteristics of sarcoidosis differ according to geographical distribution. The aim of our study was to disclose epidemiological characteristics in our country. The data was collected from investigators, who sent information on newly-diagnosed patients via internet. In 2 years 198 female and 95 male patients were enrolled to the study (f/m:2.08). Mean age of patients was 44+/-13 years (17-90). Mean age of male patients was 38+/-12 while mean age of female patients was 48+/-13 (p<0.001). 73.4% of patients were nonsmokers (85.4% of females; 48.4% of males; (p<0.001)). About 50% of our 293 patients were housewives. Familial sarcoidosis was found in 3 patients' first degree relatives. Estimated annual incidence of sarcoidosis for Turkey was calculated as 4 per 100,000 person. According to our study, 2/3 of sarcoidosis patients were women; mean age of patients was 45 and the disease began 10 years later in female patients. 80% of patients were nonsmokers; negative relation between sarcoidosis and smoking was evident especially in women. Familial sarcoidosis frequency was lower compared to other studies in the literature. There was no occupational exposure history in our patients. Our incidence rate, is similar with the results of other European studies.

Use of oral glucose minimal model–derived index of insulin sensitivity in subjects with early type 1 diabetes mellitus

Insulin resistance plays an important role during various stages of the type 1 diabetes mellitus disease process. Unfortunately, many of the techniques used to measure insulin sensitivity are experimentally laborious and time-consuming and are thus impractical for larger clinical and population studies. Therefore, in this study, we obtain estimates of insulin sensitivity from a simpler experiment, the oral glucose tolerance test (OGTT), and compare them with those from a frequently sampled intravenous glucose tolerance test (FSIGT) in a population of subjects defined as having early type 1 diabetes mellitus (abnormal 2-hour glucose on OGTT) and a group of healthy controls. A total of 19 subjects were studied. Eight antibody-positive first- or second-degree relatives of patients with type 1 diabetes mellitus and 11 healthy controls underwent both a 3-hour OGTT and an insulin-modified FSIGT on separate days. Indices of insulin sensitivity ( S I) were estimated from the recently derived oral glucose minimal model and the original minimal model of glucose kinetics for the OGTT and FSIGT, respectively. Estimates of S I from the OGTT correlated closely with those from the FSIGT in both early type 1 diabetes mellitus ( r s=0.76, P = .04) and healthy control ( r s = 0.67, P = .03) populations. This preliminary study demonstrates the usefulness of OGTT-derived estimates of insulin sensitivity in an early type 1 diabetes mellitus population. Given the simplicity of the OGTT relative to the traditional methods of measuring S I, the oral glucose minimal model may be appropriate for large population studies and clinical trials.

A common genetic background for inflammatory bowel disease and ankylosing spondylitis: A genealogic study in Iceland

Patients with ankylosing spondylitis (AS) and approximately 50% of their first-degree relatives may have a genetic abnormality that results in subclinical intestinal inflammation. This study was undertaken to examine the familial occurrence and cosegregation of AS and inflammatory bowel disease (IBD) in order to determine whether there is a shared genetic risk factor in families. The Icelandic genealogy database and population-wide data on all living Icelanders diagnosed as having AS (n = 205) and/or IBD (n = 1,352) were used to estimate the risk ratios of AS for relatives of patients with AS, the risk ratios of IBD for relatives of patients with IBD, and the cross-risk ratios of AS for relatives of patients with IBD or of IBD for relatives of patients with AS. The mean kinship coefficients for each disease were calculated. The control population for disease risk calculations comprised 10,000-100,000 sets of matched Icelandic subjects. First-, second-, and third-degree relatives of patients with AS had risk ratios of 94, 25, and 3.5, respectively, indicating an increased risk of developing AS (each P < 0.0005), while first-, second-, and third-degree relatives of patients with IBD had risk ratios for IBD of 4.4, 2.2, and 1.4, respectively (each P < 0.0001). The cross-risk ratios of IBD were 3.0 and 2.1 in first- and second-degree relatives of patients with AS, respectively, and were the same for AS in first- and second-degree relatives of patients with IBD. With the exception of Crohn's disease, the risk of having AS, ulcerative colitis, or IBD in spouses of patients with these diseases did not differ significantly from that in controls. Calculation of the kinship coefficients confirmed these patterns of familial risk. Patients with AS or IBD in Iceland are significantly more related to each other than are randomly sampled control subjects, in terms of an increased risk of either or both conditions developing in third-degree relatives. These findings suggest that one or more undiscovered genetic variants may underlie the risk of both diseases.

AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease

Celiac disease is a permanent intolerance to gluten, a term that is broadly used to describe the storage proteins in wheat, rye, and barley. Celiac disease is characterized by a chronic inflammatory state of the proximal small intestinal mucosa, which can impair digestion and absorption of macronutrients and micronutrients and results in increased net secretion of water and solute. Celiac disease can present with intestinal symptoms, can present with extraintestinal symptoms (including the intensely pruritic skin rash dermatitis herpetiformis), or may be detected in individuals who are asymptomatic as part of the screening of populations at increased risk for celiac disease. There is a spectrum of small intestinal mucosal injury that ranges from minimal with an increase in intraepithelial lymphocytes to total villous atrophy. However, most symptomatic patients with celiac disease have some degree of villous atrophy. The HLA class II DQ molecules DQ2 or DQ8 are necessary, although not sufficient, for the phenotypic expression of celiac disease.

Two first-degree relatives with perimesencephalic nonaneurysmal hemorrhage

Perimesencephalic (or pretruncal) nonaneurysmal hemorrhage (PMH) constitutes about 10% of all episodes of subarachnoid hemorrhage (SAH). The estimated incidence of the disease is 0.6 per 100,000 persons per year.1 PMH, first described in 1985, is characterized by accumulation of subarachnoidal blood predominantly within the prepontine cistern and absence of aneurysm or other bleeding source on angiography.2 Contrary to aneurysmal SAH, the clinical course of PMH is usually uneventful, not complicated by rebleeding or delayed cerebral ischemia, and the outcome of PMH is excellent.1 Studies evaluating the risk of first- and second-degree relatives of patients with SAH focus on aneurysmal SAH, showing a positive family history in 7 to 20% in case-control series.3 Although the exact etiology of PMH is still unclear, it is clinically and pathophysiologically distinct from aneurysmal SAH. Familial predisposition or genetic susceptibility factors are not known. We present two first-degree relatives with PMH, suggesting a …

Effects of Oral Insulin in Relatives of Patients With Type 1 Diabetes

This randomized, double-masked, placebo-controlled clinical trial tested whether oral insulin administration could delay or prevent type 1 diabetes in nondiabetic relatives at risk for diabetes. We screened 103,391 first- and second-degree relatives of patients with type 1 diabetes and analyzed 97,273 samples for islet cell antibodies. A total of 3,483 were antibody positive; 2,523 underwent genetic, immunological, and metabolic staging to quantify risk of developing diabetes; 388 had a 5-year risk projection of 26-50%; and 372 (median age 10.25 years) were randomly assigned to oral insulin (7.5 mg/day) or placebo. Oral glucose tolerance tests were performed every 6 months. The median follow-up was 4.3 years, and the primary end point was diagnosis of diabetes. Diabetes was diagnosed in 44 oral insulin and 53 placebo subjects. Annualized rate of diabetes was similar in both groups: 6.4% with oral insulin and 8.2% with placebo (hazard ratio 0.764, P = 0.189). In a hypothesis-generating analysis of a subgroup with insulin autoantibody (IAA) levels confirmed (on two occasions) > or =80 nU/ml (n = 263), there was the suggestion of benefit: annualized diabetes rate 6.2% with oral insulin and 10.4% with placebo (0.566, P = 0.015). It is possible to identify individuals at high risk for type 1 diabetes and to enroll them in a large, multisite, randomized, controlled clinical trial. However, oral insulin did not delay or prevent type 1 diabetes. Further studies are needed to explore the potential role of oral insulin in delaying diabetes in relatives similar to those in the subgroup with higher IAA levels.

Enfermedades autoinmunes y esclerosis múltiple

Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system with an unknown origin, although the immunological system plays a crucial role in its pathogenesis. It has been observed that the relatives of MS patients very often have other autoimmune diseases (ADs) and it has been suggested that there may be susceptibility genes that are common to this group of diseases.Our aim was to estimate the prevalence of ADs in first and second degree relatives of patients with MS and to determine the coexistence of other ADs in MS patients.We selected 251 patients with MS defined by the Poser criteria and face-to-face interviews with the patients and/or their relatives were conducted to investigate the following ADs: MS, rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, autoimmune thyroid disease (ATD), inflammatory bowel disease, myasthenia gravis, type I diabetes mellitus (DMI) and psoriasis. RESULTS. 29.9% of the patients with MS had a first and/or second degree relative with an AD. Prevalence of ADs in first degree relatives was 15.5%, 30% in familial MS and 40% if the patient had both MS and another AD. The most frequent ADs were: MS 27%, psoriasis 18%, ATD 16% and DMI 15%. 15 patients had MS and another AD: six ATD, three DMI, four psoriasis, one inflammatory bowel disease and one myasthenia gravis.These findings lend support to the existence of susceptibility genes that are common to the different ADs and would act as risk factors.

Characterization of mutator phenotype in familial colorectal cancer patients not fulfilling amsterdam criteria.

Although the mutator phenotype, including genetic and epigenetic alterations of the mismatch repair (MMR) system, seems to be pronounced in familial colorectal cancer, there have been few integrative studies comprising the entire mutator pathway. This study was done to identify the entire mutator pathway determining risk factors in patients with familial colorectal cancer not fulfilling the Amsterdam criteria. We consecutively recruited 134 colorectal cancer patients with a family history of accompanying cancers. Patients with hereditary nonpolyposis colorectal cancer meeting the Amsterdam criteria, familial adenomatous polyposis, or those receiving preoperative radiotherapy were excluded. Mutator phenotype was assessed by assaying microsatellite instability (MSI) at 24 markers, hMLH1-promoter methylation, mutations at MMR genes (hMLH1, hMSH2, hMSH6, and hPMS2), and immune staining of MMR proteins (hMLH1, hMSH2, hMSH6, hPMS1, and hPMS2). Of the 208 cancers in first-degree and/or second-degree relatives of patients, colorectal and gastric cancers (81%) were most common. Of the 134 proband colorectal cancers, 23 (17%) were MSI in high level, and 32 (24%) were MSI in low level. MMR alterations, including known polymorphism and splicing substitution, were identified in eight patients (6%). Twenty-eight tumors with mutator phenotype were further identified by hMLH1-promoter methylation and/or loss of MMR protein expression. In 51 tumors (38%), mutator phenotype was associated with right-sided colon cancer (P < 0.001) and younger age at onset (P=0.032), but the number of patients with a mutator phenotype did not differ with respect to inheritance patterns of accompanying cancers, either successive or horizontal transmission (P=0.815). Familial impact value, which differentially associated the degree of relatives with all accompanying cancers, effectively discriminated MSI in high level from microsatellite stable/MSI in low level tumors. Familial colorectal cancer may be associated with multiple occurrences of colorectal or accompanying cancers inherited by dominant or recessive transmission. MMR gene mutations, however, are less associated with mutator phenotype in familial colorectal cancer.

Primary fibromyalgia and depression: The role of relatives in fibromyalgia

Abstract Objective. To compare a group of patients suffering from fibromyalgia (FM) with patients having a lumbar disc hernia (LDH) and with a control group of healthy subjects. We investigate of the presence psychiatric disorders and their relationship with FM. Psychiatric disorders were also investigated in first and second degree relatives of patients with FM. Methods. Thirty-four patients suffering from FM according to the American College of Rheumatology criteria, 30 patients with lumbar disc hernia (LDH) without fibromyalgia and 43 healthy subjects were introduced into the study. All the groups were sex and age matched. All subjects were investigated by a structured clinical interview (Diagnostic and Statistical Manual of Mental Disorders, 4th edn), by Beck depression scale (BDS), and by Hamilton depression scale (HDS). Family history research diagnostic criteria were used. Results. The mean scores of BDS and of HDS were significantly higher in FM and LDH patients than in controls. In addition, ther...

The iceberg cometh: Establishing the prevalence of celiac disease in the United States and Finland

The iceberg cometh: Establishing the prevalence of celiac disease in the United States and Finland

Family history study of the restless legs syndrome

Background: Although there is a relatively high rate of occurrence of sporadic cases of restless legs syndrome (RLS), the systematic study of family history of RLS in populations of RLS patients has been very limited. The objective of the present study was to determine the risk of RLS for first- and second-degree relatives of a population of primary RLS patients not selected for the number of affected relatives in their families and to obtain an estimate of the degree of genetic involvement in RLS. Methods: Consecutively consenting patients from two different sites who met the criteria for RLS completed a worksheet that asked them to indicate their current age, the date of their earliest RLS symptoms, and the names and RLS status of all of their first- and second-degree relatives. Controls with no clinical history of RLS also completed the worksheet. Results: First- and second-degree relatives of patients with RLS had a significantly greater risk of RLS than the first- ( P<0.001 ) and second-degree relatives ( P<0.003 ) of controls. The risk of RLS was found to be greater for first-degree relatives of early-onset, rather than late-onset, RLS probands ( P<0.001 ). Conclusions: This study provides a complete systematic examination of the risk of RLS among relatives of RLS probands and controls using the same assessment methodology. Although the results are consistent with a genetic etiology for RLS, they do not support the presence of one simple, Mendelian-inherited major gene in most RLS families.

Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritis.

To determine if the prevalence of autoimmunity among relatives of patients with juvenile rheumatoid arthritis (JRA) is greater than that among relatives of healthy volunteer control subjects. Interviews were used to obtain histories of the following disorders among living first- and second-degree relatives of 110 patients and 45 controls: alopecia areata, ankylosing spondylitis, dermatomyositis, Graves' disease, Hashimoto thyroiditis, insulin-dependent diabetes mellitus, inflammatory bowel disease, iritis, JRA, multiple sclerosis, psoriasis, RA, systemic lupus erythematosus, and vitiligo. Chi-squares, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. Families of 23 JRA affected sibpairs were interviewed subsequently. There were no significant differences between patients and controls with regard to age, sex, ethnicity, or family size. Patients had 1,228 relatives and controls had 496 relatives. Of all the relatives of the patients, 155 had at least 1 autoimmune disorder, compared with 20 relatives of the controls (12.6% versus 4.0%; OR 3.4 [95% CI 2.1-5.7], P < 0.000001). The prevalence of autoimmunity was increased in first-degree and in second-degree relatives of patients (16.1% and 10.6%, respectively). The prevalence of Hashimoto thyroiditis was significantly higher in the relatives of patients (OR 3.5 [95% CI 1.6-7.9], P = 0.0008). The prevalences of other disorders were not significantly different. JRA affected sibpair families had an increased prevalence of autoimmunity (15.0%). A history of arthritis was found significantly more frequently in the JRA affected sibpair families, but not in the simplex families. These data demonstrate that the prevalence of autoimmunity is significantly higher among first- and second-degree relatives of JRA patients. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity.

Subarachnoid haemorrhage in first and second degree relatives of patients with subarachnoid haemorrhage: Bromberg JE, Rinkel GJ, Algra A, et al. BMJ. 1995;311:288-9

Subarachnoid haemorrhage in first and second degree relatives of patients with subarachnoid haemorrhage: Bromberg JE, Rinkel GJ, Algra A, et al. BMJ. 1995;311:288-9

Ferrochelatase activities in patients with erythropoietic protoporphyria and their families

Ferrochelatase, estimated as zinc chelatase, was measured in the lymphocytes of 30 patients with erythropoietic protoporphyria (EPP), in 35 first- or second-degree relatives of patients with EPP, and in 50 healthy controls. In 30 EPP patients the zinc chelatase level (mean +/- standard deviation, SD) was 0.45 +/- 0.10 nmol of zinc protoporphyrin per hour per milligram of protein, in 14 EPP carriers the zinc chelatase level (mean +/- SD) was 0.42 +/- 0.09 and in 50 healthy controls the zinc chelatase level (mean +/- SD) was 0.84 +/- 0.27. All patients with EPP were also demonstrated to have an elevated protoporphyrin level in their red blood cells: the erythrocyte protoporphyrin levels were as follows EPP patients (mean +/- SD) 1300 +/- 758 nmol protoporphyrin/dl, EPP carriers (mean +/- SD) 60 +/- 24, and healthy controls (mean +/- SD) 50 +/- 25 (P < 0.001 for EPP patients compared to controls and EPP carriers). The families of 12 out of 15 EPP patients were examined with respect to the mode of inheritance of the disorder. Of 35 relatives, 14 were carriers of EPP, as characterized by reduced zinc chelatase activity in lymphocytes and by a normal protoporphyrin level in red blood cells. None of the 14 EPP carriers had presented with clinical symptoms of EPP. The mod of inheritance was autosomal dominant in seven of the 12 examined families, and autosomal recessive in two. In two families only one parent could be investigated, but we nevertheless concluded that the inheritance was autosomal dominant. Inheritance in one EPP family could not be elucidated as both parents showed normal zinc chelatase levels and did not demonstrate abnormal erythrocyte protoporphyrin levels.

Hypertension, Stroke, and Coronary Heart Disease in Relatives of Patients With Subarachnoid Hemorrhage

First-degree relatives of patients with subarachnoid hemorrhage (SAH) have a three to seven times greater risk of SAH than second-degree relatives and than the general population. If hypertension, which is in part genetically determined, contributes to this increased risk, the frequency of hypertension and its sequelae would be expected to be higher in first- than in second-degree relatives of patients with SAH. We compared the reported frequency of hypertension, stroke, and coronary heart disease between 1290 first- and 3588 second-degree relatives of a prospective series of patients with SAH. The relative risk adjusted for age and survival status in first-degree relatives was 2.3 (95% confidence interval [CI], 1.9 to 2.9) for hypertension, 1.8 (95% CI, 1.3 to 2.4) for stroke, and 1.9 (95% CI, 1.5 to 2.3) for coronary heart disease. Hypertension is a familial factor contributing to the risk of SAH. Hypertension should be sought and treated in first-degree relatives of patients with SAH to reduce the increased risk of cerebrovascular and cardiovascular diseases.