Recent Advances in Serum Biomarkers for Risk Stratification and Patient Management in Cardio-Oncology.

PURPOSE OF REVIEW: Following significant advancements in cancer therapeutics and survival, the risk of cancer therapy-related cardiotoxicity (CTRC) is increasingly recognized. With ongoing efforts to reduce cardiovascular morbidity and mortality in cancer patients and survivors, cardiac biomarkers have been studied for both risk stratification and monitoring during and after therapy to detect subclinical disease. This article will review the utility for biomarker use throughout the cancer care continuum. RECENT FINDINGS: A recent meta-analysis shows utility for troponin in monitoring patients at risk for CTRC during cancer therapy. The role for natriuretic peptides is less clear but may be useful in patients receiving proteasome inhibitors. Early studies explore use of myeloperoxidase, growth differentiation factor 15, galectin 3, micro-RNA, and others as novel biomarkers in CTRC. Biomarkers have potential to identify subclinical CTRC and may reveal opportunities for early intervention. Further research is needed to elucidate optimal biomarkers and surveillance strategies.

Incidental findings in cone beam computed tomography volumes: Calcified head-and-neck atheromas detected during dental evaluation.

PURPOSE: Atheromas can be detected incidentally in routine dental cone beam computed tomography (CBCT) images. This study aims to assess prevalence and risk factors associated with these vascular lesions. MATERIALS AND METHODS: The maxillofacial CBCTs of 458 subjects were evaluated and divided into 4 groups based on the presence of calcified atheroma: subjects with no calcified atheroma, subjects with intracranial calcified atheroma (ICA), subjects with extracranial calcified atheroma (ECA), and subjects exhibiting combined lesions. Age, sex, medical conditions, family history, and size were documented. Analysis of variance followed by a multiple comparison test was used for data satisfying parametric test assumptions. Chi-squared tests were used to assess categorical data. The Spearman Rho test was used to assess the correlation between the incidence of calcified atheroma and subjects' medical condition. RESULTS: Of the 458 CBCTs evaluated, 29.90% presented with calcified atheroma. Calcified atheroma prevalence was significantly higher in older patients versus younger patients (p = 0.004) and in males compared to females (p = 0.004). Males were more likely to have the combination of ICA and ECA, whereas females were more likely to have ICA alone (p ≤ 0.040). Patients with calcified atheroma were significantly more likely to have a history of hyperlipidemia (p = 0.001), hypertension (p = 0.001), and myocardial infarction/coronary artery diseases (p = 0.001). Overall, patients exhibiting both intracranial and extracranial lesions were more likely to have cardiovascular risk factors (p = 0.001). CONCLUSION: Incidentally detected calcified atheromas in CBCTs are common. Subjects with combined atheroma lesions are at higher risk for cardiovascular disease. The diagnosis of incidental calcified atheromas in CBCT's warrants early referral to medical specialists, especially if there is no medical history of existing cardiovascular disease.

Beta-blockers and Ambulatory Inotropic Therapy.

BACKGROUND: Continuous infusion of ambulatory inotropic therapy (AIT) is increasingly used in patients with end-stage heart failure (HF). There is a paucity of data concerning the concomitant use of beta-blockers (BB) in these patients. METHODS: We retrospectively reviewed all patients discharged from our institution on AIT. The cohort was stratified into 2 groups based on BB use. The 2 groups were compared for differences in hospitalizations due to HF, ventricular arrhythmias and ICD therapies (shock or antitachycardia pacing). RESULTS: Between 2010 and 2017, 349 patients were discharged on AIT (95% on milrinone); 74% were males with a mean age of 61 ± 14 years. BB were used in 195 (56%) patients, whereas 154 (44%) did not receive these medications. Patients in the BB group had longer duration of AIT support compared to those in the non-BB group (141 [1-2114] vs 68 [1-690] days). After adjusting for differences in baseline characteristics and indication for AIT, patients in the BB group had significantly lower rates of hospitalizations due to HF (hazard ratio [HR] 0.61 (0.43-0.86); P = 0.005), ventricular arrhythmias (HR 0.34 [0.15-0.74]; P = 0.007) and ICD therapies (HR 0.24 [0.07-0.79]; P = 0.02). CONCLUSION: In patients with end-stage HF on AIT, the use of BB with inotropes was associated with fewer hospitalizations due to HF and fewer ventricular arrhythmias.

Left Ventricular Assist Devices in Patients With Active Malignancies.

BACKGROUND: There are limited data to guide oncology and cardiology decision-making in patients with a left ventricular assist device (LVAD) and concurrent active malignancy. OBJECTIVES: The goal of this study was to describe cancer treatment approaches, complications, and survival among patients with active cancer on LVAD support in 2 tertiary heart failure and oncology programs. METHODS: In this retrospective cohort study, LVAD databases were reviewed to identify patients with a cancer diagnosis at the time of or after LVAD implantation. We created a 3:1 matched cohort based on age, sex, etiology of cardiomyopathy, LVAD implant strategy, and INTERMACS profile stratified by site. Kaplan-Meier analysis and Cox proportional hazards models were used to compare survival between patients with cancer and non-cancer comparators. RESULTS: Among 1,123 patients who underwent LVAD implantation between 2005 and 2019, 22 patients with LVADs with active cancer and 66 matched non-cancer comparators were identified. Median age was 62 years (range 41 to 73 years); 50% of patients with cancer were African-American, and 27% were women. Prostate cancer, followed by renal cell cancer and hematologic malignancies were the most common diagnoses. There was no significant difference in unadjusted Kaplan-Meier median survival estimates from the time of LVAD placement between patients with cancer (3.53 years; 95% confidence interval [CI]: 1.41 to 5.33) and non-cancer comparators (3.03 years; 95% CI: 1.83 to 5.26; log-rank P = 0.99). In Cox proportional hazard models, cancer diagnosis as a time-varying variable was associated with a statistically significant increase in death (hazard ratio: 2.05; 95% CI: 1.03 to 4.12; P = 0.04). Patients with cancer had less gastrointestinal bleeding compared with matched non-cancer comparators (P = 0.016). Other complications were not significantly different. CONCLUSIONS: Our study provides initial feasibility and safety data and set a framework for multidisciplinary team management of patients with cancer and LVADs.

Effect of Dosage Reduction of Hypoglycemic Multidrug Regimens on the Incidences of Acute Glycemic Complications in People With Type 2 Diabetes Who Fast During Ramadan: A Randomized Controlled Trial.

Objective: We aimed to investigate the effect of dosage reduction of four hypoglycemic multidrug regimens on the incidences of acute glycemic complications in people with type 2 diabetes who fast during Ramadan. Methods: We conducted an open-label, parallel-group, randomized controlled trial at a tertiary care center in Amman, Jordan. We recruited adults with type 2 diabetes who expressed an intention to fast during Ramadan and were adherent to one of four regimens-namely: metformin and glimepiride; metformin and vildagliptin; metformin and insulin glargine U100; or, metformin, insulin glargine U100, and human regular insulin. We randomly assigned participants in a 2:1 ratio to low- or regular-dosage therapy. The primary outcomes were the incidences of hypoglycemia and hyperglycemia during the 29 days of Ramadan 2017, and the secondary outcomes were the incidences of diabetic ketoacidosis and hyperosmolar hyperglycemic state during the same period. Results: We randomly assigned 687 participants to low-dosage therapy (n = 458) or regular-dosage therapy (n = 229) and included 678 (452 and 226, respectively) in the final analysis. The incidence of hypoglycemia was lower in the low-dosage group compared with the regular-dosage group (19 [4.2%] vs. 52 [23.0%], respectively; OR, 0.15 [95% CI, 0.08-0.26]; P < 0.001). The incidence of hyperglycemia did not differ between the low- and regular-dosage groups (319 [70.6%] vs. 154 [68.1%], respectively; OR, 1.12 [95% CI, 0.79-1.58]; P = 0.5). No participants experienced diabetic ketoacidosis or hyperosmolar hyperglycemic state. Each 1% decrease in the baseline HbA1c concentration was associated with a 19.9-fold (95% CI, 9.6-41.5; P < 0.001) increase in the odds of hypoglycemia, and each 1% increase in the baseline HbA1c concentration was associated with a 15.7-fold (95% CI, 10.0-24.6; P < 0.001) increase in the odds of hyperglycemia. Conclusion: Dosage reduction decreases the incidence of hypoglycemia without a concomitant increase in the incidences of hyperglycemia, diabetic ketoacidosis, and hyperosmolar hyperglycemic state in people with type 2 diabetes who fast during Ramadan. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04237493.

Case Report: Multiple Strokes and Digital Ischemia in a Young COVID-19 Patient.

COVID-19 is an infectious disease caused by SARS-CoV-2. This enveloped RNA coronavirus primarily has tropism for the respiratory tract. However, it has also been shown to have various extrapulmonary manifestations such as pulmonary embolism, ischemic strokes, deep venous thrombosis, or arterial thrombosis. We present a case of a 34-year-old woman who had severe COVID-19 infection with no respiratory symptoms and developed strokes in multiple vascular territories and digital ischemia due to thrombosis formation in the brachial circulation of her arm despite receiving therapeutic anticoagulation.

Readmission after inferior vena cava filter placement for acute venous thromboembolism in the United States: Impact of a cancer diagnosis.

BACKGROUND: Inferior vena cava filter (IVCF) use is common after a venous thromboembolic event (VTE). Cancer is associated with higher rates of VTEs and is also seen in a significant proportion of patients requiring IVCF. As hospital readmissions remain a frequently scrutinized metric, we sought to evaluate the impact of cancer on hospital-readmission rates and in-hospital outcomes among patients with VTEs who received an IVCF. METHODS: Leveraging the 2013 to 2014 Nationwide Readmission Database, we identified adult patients presenting with a VTE in the United States and evaluated 30-day readmission rates and readmission in-hospital outcomes postindex-admission. Multivariable logistic regression was used to identify factors associated with readmission after an index-procedure, including traditional and nontraditional cardiovascular risk factors, as well as hospital-level characteristics. RESULTS: Among the 619 241 patients presenting with a VTE at index-admission, 11.2% of patients received IVCF on index-admission, of which 30.9% had cancer. The 30-day readmission rate amongst IVCF recipients was 15.8% (N = 10 927), and 19.9% amongst those with cancer compared to 13.9% in patients without cancer (P < .001). Moreover, cancer patients had longer lengths of stay in the hospital (4.5 ± 0.2 vs 4.0 ± 0.1 days; P = .02), higher cost of care ($10 900 ± 308 vs $9242 ± 206; P = .007), but no difference in mortality (8.3% vs 6.3%; P = .70) during readmission compared to noncancer patients. CONCLUSION: Readmission after IVCF placement is common. In patients readmitted after an IVCF implantation, those with cancer have longer hospital stays and higher costs of care. However, in-hospital mortality is similar to those without cancer.

Crossing Boundaries: A Rare Case of Cardiac Dysfunction.

Cardiac tumors are relatively rare. Secondary cardiac tumors are by far more common than primary cardiac tumors. Cardiac involvement may occur secondary to hematogenous metastases, direct invasion, or tumor growth into the venous system and extension into the right atrium. Patients can present with a spectrum of conditions, including embolization, obstruction of ventricular outflow tracts, direct invasion of myocardium causing impaired myocardial function, invasion of surrounding tissue, interference with valvular function causing valvular regurgitation, or constitutional non-specific signs and symptoms. Imaging modalities are essential for diagnosis. Management is mostly surgical, but can include other medical strategies as well. We present a case of a 65-year-old male with hepatocellular carcinoma with direct invasion to the heart through the venous system.

Periodontal Inflammation and the Risk of Cardiovascular Disease.

PURPOSE OF REVIEW: The role of oral bacteremia and periodontal inflammation driving atherosclerosis is still under investigation. This review article highlights the role of periodontal inflammation and oral microorganisms in the development and progression of atherosclerosis and cardiovascular diseases. RECENT FINDINGS: Association between periodontal and cardiovascular diseases has been well characterized, but causal correlation is yet to be established. For instance, untreated gingivitis can progress to periodontitis. Periodontal disease has been associated with several systemic diseases one of which is atherosclerosis. One possible association that was documented in literature is that poor oral hygiene leads to bacteremia, which in turn can cause bacterial growth over atherosclerotic coronary artery plaques and possibly worsen coronary artery disease. It is crucial that clinicians understand the association between periodontal and cardiovascular disease. A comprehensive treatment for periodontitis and re-establishment of a healthy periodontium can help in reduction of overall inflammation in the body. This may play an important role in prevention of cardiovascular disease, though future research is needed to establish this.

Racial differences in takotsubo cardiomyopathy outcomes in a large nationwide sample.

AIMS: Takotsubo cardiomyopathy (TC) is characterized by transient ventricular impairment, often preceded by emotional or physical stress. Racial differences affect the outcomes of several cardiovascular conditions; however, the effect of race on TC remains unknown. This investigation aims to assess the effect of race on in-hospital outcomes of TC in a large national sample. METHODS AND RESULTS: We conducted a US-wide analysis of TC hospitalizations from 2006 to 2014 by querying the National Inpatient Sample database for the International Classification of Diseases-ninth Revision TC code, characteristics, and inpatient outcomes. Patients with a primary diagnosis of acute coronary syndrome were excluded to reduce selection bias. Caucasians were compared with African Americans (AA) for differences in baseline characteristics and in-hospital outcomes. Multivariate regression models were created to adjust for potential confounders. Of 97 650 TC patients, 83 807 (86.9%) were women, 89 624 (91.8%) identified as Caucasians, and 8026 (8.2%) as AA. The annual number of TC hospitalizations increased significantly from 2006 to 2014 in both races (from 335 to 21 265 annual cases, P < 0.001). In-hospital mortality initially increased (1-2% in 2006 to 5-6% in 2009, P < 0.001) and subsequently remained relatively stable around 5-7% with no significant difference between races. In unadjusted analysis, AA had more cardiac arrests [304 (3.8%) vs. 2569 (2.9%), P = 0.04], invasive mechanical ventilation [1671 (20.8%) vs. 15 897 (17.7%), P = 0.002], tracheostomies [242 (3%) vs. 1600 (1.8%), P = 0.001], acute kidney injuries [1765 (22%) vs. 14 608 (16.3%), P < 0.0001], and longer hospital stays [4.5 (3.2-4.8) vs. 3.8 (3.7-3.9) days, P < 0.0001] compared with Caucasians. After the adjustment for differences in age, gender, comorbidities (using the enhanced Charlson comorbidity index), hospital location/teaching status, and socio-economic factors, all differences were significantly attenuated or eliminated. Additionally, the adjusted risk was lower in AA compared with Caucasians, for cardiogenic shock [odds ratio (OR) 0.61 (0.47-0.78), P < 0.0001], mechanical ventilation [OR 0.8 (0.70-0.92), P = 0.002] and intraaortic balloon pump insertion [OR 0.63 (0.41-0.99), P = 0.04]. CONCLUSIONS: Our investigation is the first large US-wide analysis studying racial variations in TC outcomes. AA overall have more in-hospital complications; however, the differences are driven by racial disparities in demographics, comorbidities, and socio-economic factors.

The effect of catheter-directed thrombolytic use on readmission rates and in-hospital outcomes among cancer patients with venous thromboembolism in the United States.

BACKGROUND: Cancer inducing a hypercoagulable state, venous thromboembolism (VTE) remains a leading cause of morbidity and mortality globally. We assessed the impacts of cancer on the likelihood for readmission after a VTE-targeted procedure. METHODS: We created a new cohort using discharge-level data from all hospitalizations from State Inpatient Databases of geographically dispersed participating states (18-27 states). RESULTS: In those presenting with VTE during index-admission (619 241), 2.4% patients underwent catheter directed thrombolytic therapy (CDL) on index admission and among those 20.3% had cancer. Moreover, the 30-day readmission rate amongst CDL recipients (10 776 overall) was 14.3% in those with cancer compared to 8.8% in those with no cancer history (P < .0001). Additionally, in-hospital mortality (5.7% vs 1.1%; P = 0.009) and cost-of-care ($11 014 ± 914 vs $10 520 ± 534; P = .04) was significantly higher in cancer compared to noncancer. CONCLUSION: The use of CDL does not appear to reduce the risk of returning for a VTE-related admission in cancer.

Usefulness of Malignancy as a Predictor of WorseIn-Hospital Outcomes in Patients With Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TC) is a form of dilated cardiomyopathy often associated with physical or emotional stress. Association with cancer has been reported, however, in-hospital outcomes in TC patients with history of malignancy have not been fully characterized. We conducted a retrospective chart review of hospitalized patients with diagnosis of TC between January 2006 and January 2017. Patients were divided into 2 groups based on the previous history of malignancy. Presenting symptoms, cardiac imaging and short-term events including in-hospital complications and mortality, were compared. Of 318 patients with TC, 81 (25.4%) had a previous diagnosis of cancer. Mean age was 67.5 (SD 12.6), 151 (47.5%) were African American, 122 (38.4%) Caucasian, and 10 (3.1%) of other ethnicities. Patients with history of malignancy were older (70.0 [SD 10.6] vs 66.6 [SD 13.1] years, p = 0.03), had higher heart rate on presentation (93 [SD 19] vs 87 [SD 25] beats/minute, p = 0.03), higher prevalence of severely decreased cardiac function (left ventricular ejection fraction <25%) (29.6% vs 16%, p = 0.01), longer hospitalization (7 (4-13) vs 4 (3-8) days, p = 0.001) and experienced more in-hospital cardiac arrests (6 [7.4%] vs 5 [2.1%], p = 0.035) compared with patients without malignancy history. Higher percentage of longer hospitalization and left ventricular ejection fraction <25% in the cancer group persisted after controlling for sepsis, chemotherapy exposure, and metastatic disease. In conclusion, in a racially diverse hospitalized population of TC, prevalence of cancer history is high, and diagnosis of previous malignancy is associated with adverse in-hospital outcomes.

Heart Failure in Relation to Anthracyclines and Other Chemotherapies.

Anthracyclines are the cornerstone of therapy for a wide range of solid and hematologic malignancies; however, their use is limited by the risk of chemotherapy-induced cardiotoxicity leading to cardiomyopathy and heart failure. The incidence of cardiotoxicity in the literature depends on the definition being used, anthracycline dose, duration of follow-up, and surveillance methods used to identify cardiac injury. The reported risk of clinical heart failure has been around 2% to 4% with low-dose anthracycline regimens, whereas the incidence of cardiac injury defined by an abnormal increase in cardiac biomarkers has been reported as high as 35%. Multiple mechanisms have been proposed for anthracycline cardiotoxicity, including the deleterious effects of oxidative stress and reactive oxygen species and the inhibition of topoisomerase II beta, which leads to cardiomyocyte death. In addition, genetic susceptibility is an emerging field that is currently generating active research. The risk factors associated with anthracycline cardiotoxicity include lifetime cumulative dose, age, prior cardiac dysfunction, and the presence of cardiovascular risk factors, in particular hypertension. In this review, we summarize the incidence, mechanisms, and risk factors for anthracycline-mediated left ventricular dysfunction and discuss the role of risk stratification and early detection in patient management.

Heart Failure in Relation to Tumor-Targeted Therapies and Immunotherapies.

Tumor-targeted therapies such as trastuzumab have led to significant improvements in survival of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, these therapies have also been associated with significant left ventricular dysfunction. The incidence of trastuzumab-induced heart failure has decreased significantly since the initial reports, in large part due to improved screening, closer monitoring for early changes in left ventricular function, and a significant decrease in the concurrent administration of anthracyclines. The mechanism of trastuzumab cardiotoxicity is still not well understood, but current knowledge suggests that ErbB2 inhibition in cardiac myocytes plays a key role. In addition to trastuzumab and other HER2-targeted agents, vascular endothelial growth factor inhibitors, proteasome inhibitors, and immune checkpoint inhibitors are all additional classes of drugs used with great success in the treatment of solid tumors and hematologic malignancies. Yet these, too, have been associated with cardiac toxicity that ranges from a mild asymptomatic decrease in ejection fraction to fulminant myocarditis. In this review, we summarize the cardiotoxic effects of tumor-targeted and immunotherapies with a focus on HER2 antagonists.

Large-caliber metal stents versus plastic stents for the management of pancreatic walled-off necrosis.

BACKGROUND AND AIMS: Symptomatic pancreatic walled-off necrosis (WON) may be managed by endoscopic transmural drainage and endoscopic transmural necrosectomy, with stent placement at endoscopic drainage sites. The optimal stent choice is yet to be determined. We compared outcomes after endoscopic management of WON using either large-caliber fully covered self-expandable metal stents (LC-SEMSs) or double-pigtail plastic stents (DPPSs). METHODS: We performed a retrospective comparison of outcomes among patients who received LC-SEMSs or DPPSs before endoscopic transmural necrosectomy for WON. RESULTS: Among 94 patients included, WON resolution rates did not differ between the DPPS (36 patients) and LC-SEMS (58 patients) groups, whether concomitant percutaneous drainage was considered a failure (75% vs 82.8%; P = .36) or not (91.7% vs 94.8%; P = .55). Of 75 patients (80%) successfully treated without percutaneous drainage, 37 (49%) underwent endoscopic transmural drainage without subsequent endoscopic transmural necrosectomy. WON was more likely to resolve without subsequent endoscopic transmural necrosectomy in the LC-SEMS group than the DPPS group (60.4% vs 30.8%; P = .01). WON resolution without subsequent endoscopic transmural necrosectomy remained more likely with LC-SEMSs (odds ratio, 4.5 [95% confidence interval, 1.5-15.5]) after adjusting for patient age and size and location of WON. Rates of adverse events were similar except for clinically significant bleeding requiring endoscopic intervention, which was higher with DPPSs than LC-SEMSs (14% vs 2%; P = .02). CONCLUSION: Management of pancreatic WON with LC-SEMSs appears to decrease both the need for repeated necrosectomy procedures and the risk of intervention-related hemorrhage.

Safety and efficacy of coaxial lumen-apposing metal stents in the management of refractory gastrointestinal luminal strictures: a multicenter study.

BACKGROUND AND AIMS: Benign gastrointestinal (GI) strictures are often refractory to standard endoscopic interventions. Fully covered coaxial lumen-apposing metal stents (LAMS) have emerged as a novel therapy for these strictures. The aim of this study was to evaluate the safety and efficacy of LAMS for refractory GI strictures. PATIENTS AND METHODS: A retrospective analysis was performed for patients who underwent LAMS placement for benign luminal strictures in three US centers between January 2014 and December 2016. The primary outcomes were technical success and initial clinical success of LAMS placement. Secondary outcomes were stent migration, rate of re-intervention, and adverse events. RESULTS: A total of 49 patients underwent 56 LAMS placement procedures. Previous treatment had failed in 39 patients (79.6 %), and anastomotic strictures were the indication in 77.6 % (38/49), with the most common site being gastrojejunal (34.7 % [17/49]). Technical success was achieved in all procedures and initial clinical success was achieved in 96.4 % of all procedures (54/56). Patient initial clinical success was 95.9 % (47/49). Stent migration occurred in 17.9 % of procedures, and was more likely to occur at sites in the lower GI tract ( P  = 0.02). The mean stent dwell time was 100.6 days, and the mean follow-up was 169.8 days. Minor adverse events, not requiring hospitalization, occurred in 33.9 % of procedures, including subsequent stricture progression (10.7 %). In cases where LAMS were removed, mean follow-up time was 102.2 days. The re-intervention rate was 75 % at 300 days follow-up after stent removal. Of the LAMS placed at anastomotic strictures, 36.4 % required re-intervention, with approximately two-thirds of these re-interventions requiring placement of a new stent or surgery. CONCLUSION: LAMS placement was successful for the management of refractory GI strictures, with good technical and initial clinical success rates. However, re-intervention rates after LAMS removal were high, and many strictures were not resolved by an extended period of stenting with these coaxial stents. LAMS placement offers additional therapeutic options and in selected cases might be considered a destination therapy for patients with recalcitrant benign strictures.

Consanguinity and the Risk of Hashimoto's Thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease that may lead to hypothyroidism due to progressive destruction of the thyroid. The etiology of HT is unclear. However, it is associated with multiple genetic predispositions. Consanguinity has been associated with an increased susceptibility to different inherited conditions. This study investigated the association between consanguinity and risk of HT for the first time. METHODS: Using a case-control study design, 298 HT patients were compared with two subject groups: (i) 299 participants with non-HT hypothyroidism, and (ii) 298 healthy control participants. The three groups were age and sex matched. Presence of consanguinity among the parents was compared in these groups, and odds ratios (OR) were calculated to establish a correlation. RESULTS: Consanguinity significantly increased the risk of HT (compared with healthy subjects; OR = 3.3; p < 0.0001). In addition, consanguinity was a significant risk factor for HT compared with non-HT hypothyroidism patients (OR = 2.8; p < 0.0001). However, the prevalence of consanguinity was not significantly different in non-HT hypothyroidism patients and healthy subjects. CONCLUSIONS: The results suggest that the risk for HT is increased in consanguineous unions, but no significant increase in the risk of non-HT hypothyroidism was observed. However, for more precise risk estimates, larger studies that include different populations may be helpful. These findings highlight the health impact of consanguinity and have applications in empiric risk estimations in genetic counseling, particularly in countries with high rates of consanguineous marriages.