Gastroesophageal reflux disease (GERD) is a complex condition with diverse clinical presentations, ranging from typical heartburn and regurgitation symptoms to extraesophageal manifestations and alarm symptoms. Determining which patients should be tested first versus those who should receive empirical treatment remains a key clinical challenge. If not recently performed, initial patient testing, commonly involving upper endoscopy, is recommended for patients presenting with alarm or refractory symptoms and for those at high risk for Barrett’s esophagus. Additionally, testing should be prioritized for patients with underlying comorbidities, such as scleroderma, increased body mass index, or a suspected large hiatal hernia. Older patients with atypical symptom presentations and those with extraesophageal symptoms or signs, especially in the absence of typical GERD symptoms, should also be referred for endoscopy if recent endoscopic results are not available. In contrast, patients with typical GERD symptoms in the absence of alarm features and those with extraesophageal symptoms accompanied by typical GERD symptoms could begin empirical treatment with a proton pump inhibitor (PPI) or potassium competitive acid blocker (PCAB). For individuals without alarm symptoms who do not respond to once-daily PPI therapy, escalation to twice-daily PPI therapy or switching to a PCAB, without further testing, is appropriate. Overall, an individualized approach is recommended, with patient presentation guiding the decision to test or treat first.

Purpose: Cardiovascular disease (CVD) is more prevalent in men than women, but the mechanisms responsible for this are not fully understood. We aimed to evaluate differences in trimethylamine (TMA), a microbial metabolite and its oxidized form, trimethylamine N-oxide (TMAO), which is thought to promote atherosclerosis, between men and women with coronary heart disease (CHD), using as a reference a non-CVD population. Materials and Methods: This study was carried out within the framework of the CORDIOPREV study (NCT00924937; June 19, 2009), a clinical trial which included 827 men and 175 women with CHD, with a non-CVD population of 375 individuals (270 men and 105 women) as a reference group. Plasma TMA and TMAO were measured by HPLC-MS/MS. The carotid study was ultrasonically assessed bilaterally by the quantification of intima-media thickness of both common carotid arteries (IMT-CC). Results: We found higher TMAO levels and TMAO/TMA ratio in CHD men than CHD women (p=0.034 and p=0.026, respectively). No TMA sex differences were found in CHD patients. The TMA and TMAO levels and TMAO/TMA ratio were lower, and no differences between sexes were found in the non-CVD population. TMAO levels in CHD patients were consistent with higher IMT-CC and more carotid plaques (p=0.032 and p=0.037, respectively) and lower cholesterol efflux in CHD men than CHD women (p<0.001). Conclusions Our results suggest that CHD men have augmented TMAO levels compared with CHD women, presumably as a consequence of higher rate of TMA to TMAO oxidation, which could be associated with CVD, as these sex differences are not observed in a non-CVD population.

Gastroesophageal reflux disease (GERD) is a complex condition with diverse clinical presentations, ranging from typical heartburn and regurgitation symptoms to extraesophageal manifestations and alarm symptoms. Determining which patients should be tested first versus those who should receive empirical treatment remains a key clinical challenge. If not recently performed, initial patient testing, commonly involving upper endoscopy, is recommended for patients presenting with alarm or refractory symptoms and for those at high risk for Barrett’s esophagus. Additionally, testing should be prioritized for patients with underlying comorbidities, such as scleroderma, increased body mass index, or a suspected large hiatal hernia. Older patients with atypical symptom presentations and those with extraesophageal symptoms or signs, especially in the absence of typical GERD symptoms, should also be referred for endoscopy if recent endoscopic results are not available. In contrast, patients with typical GERD symptoms in the absence of alarm features and those with extraesophageal symptoms accompanied by typical GERD symptoms could begin empirical treatment with a proton pump inhibitor (PPI) or potassium competitive acid blocker (PCAB). For individuals without alarm symptoms who do not respond to once-daily PPI therapy, escalation to twice-daily PPI therapy or switching to a PCAB, without further testing, is appropriate. Overall, an individualized approach is recommended, with patient presentation guiding the decision to test or treat first.

Purpose: Cardiovascular disease (CVD) is more prevalent in men than women, but the mechanisms responsible for this are not fully understood. We aimed to evaluate differences in trimethylamine (TMA), a microbial metabolite and its oxidized form, trimethylamine N-oxide (TMAO), which is thought to promote atherosclerosis, between men and women with coronary heart disease (CHD), using as a reference a non-CVD population. Materials and Methods: This study was carried out within the framework of the CORDIOPREV study (NCT00924937; June 19, 2009), a clinical trial which included 827 men and 175 women with CHD, with a non-CVD population of 375 individuals (270 men and 105 women) as a reference group. Plasma TMA and TMAO were measured by HPLC-MS/MS. The carotid study was ultrasonically assessed bilaterally by the quantification of intima-media thickness of both common carotid arteries (IMT-CC). Results: We found higher TMAO levels and TMAO/TMA ratio in CHD men than CHD women (p=0.034 and p=0.026, respectively). No TMA sex differences were found in CHD patients. The TMA and TMAO levels and TMAO/TMA ratio were lower, and no differences between sexes were found in the non-CVD population. TMAO levels in CHD patients were consistent with higher IMT-CC and more carotid plaques (p=0.032 and p=0.037, respectively) and lower cholesterol efflux in CHD men than CHD women (p<0.001). Conclusions Our results suggest that CHD men have augmented TMAO levels compared with CHD women, presumably as a consequence of higher rate of TMA to TMAO oxidation, which could be associated with CVD, as these sex differences are not observed in a non-CVD population.

Gastroesophageal reflux disease (GERD) is a complex condition with diverse clinical presentations, ranging from typical heartburn and regurgitation symptoms to extraesophageal manifestations and alarm symptoms. Determining which patients should be tested first versus those who should receive empirical treatment remains a key clinical challenge. If not recently performed, initial patient testing, commonly involving upper endoscopy, is recommended for patients presenting with alarm or refractory symptoms and for those at high risk for Barrett’s esophagus. Additionally, testing should be prioritized for patients with underlying comorbidities, such as scleroderma, increased body mass index, or a suspected large hiatal hernia. Older patients with atypical symptom presentations and those with extraesophageal symptoms or signs, especially in the absence of typical GERD symptoms, should also be referred for endoscopy if recent endoscopic results are not available. In contrast, patients with typical GERD symptoms in the absence of alarm features and those with extraesophageal symptoms accompanied by typical GERD symptoms could begin empirical treatment with a proton pump inhibitor (PPI) or potassium competitive acid blocker (PCAB). For individuals without alarm symptoms who do not respond to once-daily PPI therapy, escalation to twice-daily PPI therapy or switching to a PCAB, without further testing, is appropriate. Overall, an individualized approach is recommended, with patient presentation guiding the decision to test or treat first.

Purpose: Cardiovascular disease (CVD) is more prevalent in men than women, but the mechanisms responsible for this are not fully understood. We aimed to evaluate differences in trimethylamine (TMA), a microbial metabolite and its oxidized form, trimethylamine N-oxide (TMAO), which is thought to promote atherosclerosis, between men and women with coronary heart disease (CHD), using as a reference a non-CVD population. Materials and Methods: This study was carried out within the framework of the CORDIOPREV study (NCT00924937; June 19, 2009), a clinical trial which included 827 men and 175 women with CHD, with a non-CVD population of 375 individuals (270 men and 105 women) as a reference group. Plasma TMA and TMAO were measured by HPLC-MS/MS. The carotid study was ultrasonically assessed bilaterally by the quantification of intima-media thickness of both common carotid arteries (IMT-CC). Results: We found higher TMAO levels and TMAO/TMA ratio in CHD men than CHD women (p=0.034 and p=0.026, respectively). No TMA sex differences were found in CHD patients. The TMA and TMAO levels and TMAO/TMA ratio were lower, and no differences between sexes were found in the non-CVD population. TMAO levels in CHD patients were consistent with higher IMT-CC and more carotid plaques (p=0.032 and p=0.037, respectively) and lower cholesterol efflux in CHD men than CHD women (p<0.001). Conclusions Our results suggest that CHD men have augmented TMAO levels compared with CHD women, presumably as a consequence of higher rate of TMA to TMAO oxidation, which could be associated with CVD, as these sex differences are not observed in a non-CVD population.

Gastroesophageal reflux disease (GERD) is a complex condition with diverse clinical presentations, ranging from typical heartburn and regurgitation symptoms to extraesophageal manifestations and alarm symptoms. Determining which patients should be tested first versus those who should receive empirical treatment remains a key clinical challenge. If not recently performed, initial patient testing, commonly involving upper endoscopy, is recommended for patients presenting with alarm or refractory symptoms and for those at high risk for Barrett’s esophagus. Additionally, testing should be prioritized for patients with underlying comorbidities, such as scleroderma, increased body mass index, or a suspected large hiatal hernia. Older patients with atypical symptom presentations and those with extraesophageal symptoms or signs, especially in the absence of typical GERD symptoms, should also be referred for endoscopy if recent endoscopic results are not available. In contrast, patients with typical GERD symptoms in the absence of alarm features and those with extraesophageal symptoms accompanied by typical GERD symptoms could begin empirical treatment with a proton pump inhibitor (PPI) or potassium competitive acid blocker (PCAB). For individuals without alarm symptoms who do not respond to once-daily PPI therapy, escalation to twice-daily PPI therapy or switching to a PCAB, without further testing, is appropriate. Overall, an individualized approach is recommended, with patient presentation guiding the decision to test or treat first.

Purpose: Cardiovascular disease (CVD) is more prevalent in men than women, but the mechanisms responsible for this are not fully understood. We aimed to evaluate differences in trimethylamine (TMA), a microbial metabolite and its oxidized form, trimethylamine N-oxide (TMAO), which is thought to promote atherosclerosis, between men and women with coronary heart disease (CHD), using as a reference a non-CVD population. Materials and Methods: This study was carried out within the framework of the CORDIOPREV study (NCT00924937; June 19, 2009), a clinical trial which included 827 men and 175 women with CHD, with a non-CVD population of 375 individuals (270 men and 105 women) as a reference group. Plasma TMA and TMAO were measured by HPLC-MS/MS. The carotid study was ultrasonically assessed bilaterally by the quantification of intima-media thickness of both common carotid arteries (IMT-CC). Results: We found higher TMAO levels and TMAO/TMA ratio in CHD men than CHD women (p=0.034 and p=0.026, respectively). No TMA sex differences were found in CHD patients. The TMA and TMAO levels and TMAO/TMA ratio were lower, and no differences between sexes were found in the non-CVD population. TMAO levels in CHD patients were consistent with higher IMT-CC and more carotid plaques (p=0.032 and p=0.037, respectively) and lower cholesterol efflux in CHD men than CHD women (p<0.001). Conclusions Our results suggest that CHD men have augmented TMAO levels compared with CHD women, presumably as a consequence of higher rate of TMA to TMAO oxidation, which could be associated with CVD, as these sex differences are not observed in a non-CVD population.

Gastroesophageal reflux disease (GERD) is a complex condition with diverse clinical presentations, ranging from typical heartburn and regurgitation symptoms to extraesophageal manifestations and alarm symptoms. Determining which patients should be tested first versus those who should receive empirical treatment remains a key clinical challenge. If not recently performed, initial patient testing, commonly involving upper endoscopy, is recommended for patients presenting with alarm or refractory symptoms and for those at high risk for Barrett’s esophagus. Additionally, testing should be prioritized for patients with underlying comorbidities, such as scleroderma, increased body mass index, or a suspected large hiatal hernia. Older patients with atypical symptom presentations and those with extraesophageal symptoms or signs, especially in the absence of typical GERD symptoms, should also be referred for endoscopy if recent endoscopic results are not available. In contrast, patients with typical GERD symptoms in the absence of alarm features and those with extraesophageal symptoms accompanied by typical GERD symptoms could begin empirical treatment with a proton pump inhibitor (PPI) or potassium competitive acid blocker (PCAB). For individuals without alarm symptoms who do not respond to once-daily PPI therapy, escalation to twice-daily PPI therapy or switching to a PCAB, without further testing, is appropriate. Overall, an individualized approach is recommended, with patient presentation guiding the decision to test or treat first.

Purpose: Cardiovascular disease (CVD) is more prevalent in men than women, but the mechanisms responsible for this are not fully understood. We aimed to evaluate differences in trimethylamine (TMA), a microbial metabolite and its oxidized form, trimethylamine N-oxide (TMAO), which is thought to promote atherosclerosis, between men and women with coronary heart disease (CHD), using as a reference a non-CVD population. Materials and Methods: This study was carried out within the framework of the CORDIOPREV study (NCT00924937; June 19, 2009), a clinical trial which included 827 men and 175 women with CHD, with a non-CVD population of 375 individuals (270 men and 105 women) as a reference group. Plasma TMA and TMAO were measured by HPLC-MS/MS. The carotid study was ultrasonically assessed bilaterally by the quantification of intima-media thickness of both common carotid arteries (IMT-CC). Results: We found higher TMAO levels and TMAO/TMA ratio in CHD men than CHD women (p=0.034 and p=0.026, respectively). No TMA sex differences were found in CHD patients. The TMA and TMAO levels and TMAO/TMA ratio were lower, and no differences between sexes were found in the non-CVD population. TMAO levels in CHD patients were consistent with higher IMT-CC and more carotid plaques (p=0.032 and p=0.037, respectively) and lower cholesterol efflux in CHD men than CHD women (p<0.001). Conclusions Our results suggest that CHD men have augmented TMAO levels compared with CHD women, presumably as a consequence of higher rate of TMA to TMAO oxidation, which could be associated with CVD, as these sex differences are not observed in a non-CVD population.