Re: Mauro Gacci, Giovanni Corona, Arcangelo Sebastianelli, et al. Male Lower Urinary Tract Symptoms and Cardiovascular Events: A Systematic Review and Meta-analysis.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.

Gacci et al [1] recently presented a remarkable review of the relationship between male lower urinary tract symptoms (LUTS) and major adverse cardiac events (MACE). Considering the rates of LUTS/benign prostatic hyperplasia (BPH) and cardiovascular disease (CVD) associated with noncommunicable diseases and the use of holistic health care in this era of aging societies, this is an important issue. Although the authors’ review was thorough and included scientific analysis, some points remain to be clarified.

First, although there is no controversy about the relationship between metabolic syndrome (MS) and CVD aggravation, the link between MS and LUTS remains inconclusive. Besides the well-known complicated relationship between male LUTS and MS, which includes factors such as prostate enlargement, insulin resistance, dyslipidemia, hyperinsulinemia, autonomic sympathetic overactivity, and consequent endothelial and smooth muscle dysfunction, MS itself is a combination of multiple diseases or conditions influenced by multiple factors, including age, obesity, fatty liver, and hormonal factors [2]. There is mixed evidence regarding the relationship between male LUTS and MS.

Second, the authors focused heavily on BPH to explain the link between LUTS and MACE, but mounting evidence suggests that storage symptoms are the dominant symptoms in patients with obesity or MS via ischemic mechanisms related to atherosclerosis [3]. Increasing evidence is revealing that among LUTS, storage symptoms are closely related to obesity, MS, and atherosclerosis.

Lastly, the interpretation of the meta-regression should include a more objective discussion of the impact of mean age on MACE. Meta-regression during meta-analysis could not provide information on potent risk factors, as could ordinary multiple regression analysis. In order for age to be an independent factor in meta-regression analysis, the age range of the patients also has to be considered because mean age itself is a secondary data point. Although the meta-regression analysis showed that age had a negative effect on MACE in moderate to severe LUTS, it may also be the case that patients in weighted studies were simply relatively younger in mean age than those in nonweighted studies.

To address these questionable points and to clarify the consistency of the relationship between male LUTS and CVD, a meta-analysis using continuous variables (eg, questionnaire scores for LUTS and CVD risk scores for MACE) is needed, as continuous variables would provide firmer information than discrete variables [4]. Another solution involves studying healthy cohorts or performing well-designed randomized controlled trials (RCTs). The fundamental reason for analyzing healthy cohorts is to avoid the complicated effects of confounding factors, which cannot be controlled for except in an RCT. To explain the role of LUTS in predicting CVD aggravation, C-reactive protein (CRP), a validated marker for the degree of MS and atherosclerosis, could be examined [5]. Kim et al [5] reported that healthy men with low CRP levels have a greater tendency to have lower storage symptom scores after adjustment for age, obesity, prostate size, and metabolic risk factors in comparison to men with normal CRP levels, which implies that subclinical inflammation plays a role in the pathophysiology of storage symptoms.