Association between Height and Hypertension: A Retrospective Study

Round 1

Reviewer 1 Report

the authors should completely review the introduction, the relationship with weight and BMI and hypertensive risk should also be included.

in the materials and methods it is necessary to better describe the recruitment, it seems to me that there are so many people recruited.

the discussion also needs to be reviewed in light of the relationship between weight and BMI as well as height

Author Response

Reviewer 1

 

Thank you for your valuable comment. A made reply for those valuable comments.

 

(Comment 1) the authors should completely review the introduction, the relationship with weight and BMI and hypertensive risk should also be included.

→ Thank you for valuable comment. According to this valuable comment, I re-check the potential mechanism that might underlying present results and the meaning of body mass index for our study.

Even the mechanisms underlying the association between height and hypertension have not been clarified, there are same mechanisms that could explain the association between height and hypertension. Those are productivity of hematopoietic stem cell, presence of low grades inflammation, and genetic factors. Then from the view of potential mechanism, BMI never explains present results and BMI is not candidates that explain present results. Then I added following sentences with same references. To avoid mead readers, I did not add the description of wight and BMI in introduction section as like previous studies [1-3].

 

Productivity of hematopoietic stem cells, presence of low grade chronic inflammation, and genetic factors are potential candidates that explain the inverse association between height and hypertension [4,5].

 

However, I also could understand the potential confounding influence on weight and BMI on present analysis. Then I added following sentences in statistical analysis section that evaluate the association between BMI and height.

 

To clarify the influence of height on body mass index (BMI), simple correlation analysis was performed.

 

And in result section, I showed the correlation between height and BMI in present study population as following.

For men, baseline height was not significantly correlated with baseline BMI. However, for women, slightly but significant correlation between baseline height and baseline BMI was observed. The simple correlation coefficient for height and BMI were -0.02 (p=0.164) for men and -0.14 (p<0.001) for women.

Therefore, BMI and weight could not act as a determinant on present analysis. However, BMI could act as a confounding factor. Then I added following sentence and added BMI as a confounding factor in multivariable model.

 

BMI is a value derived from the weight and height of a person. Our previous retrospective study with Japanese worker reported positive association between over-weight defined as baseline BMI≥25kg/m² and incidence of height loss [8]. Since BMI is strongly associated with hypertension [9], BMI could influence on the association between baseline hypertension and height loss. Then, for the second model (multivariable model), we included several other potential confounding factors with BMI (kg/m²), namely drinking status (none, often, daily), smoking status (never, former, current smoker), BMI, HbA1c (%), total cholesterol (mg/dL), glucose-lowering medication use (no, yes), and use of medication for dyslipidemia (no, yes).

 

(Comment 2) in the materials and methods it is necessary to better describe the recruitment, it seems to me that there are so many people recruited.

→ Thank you for valuable comment. According to this valuable comment, I added following sentences in study population section.

Since the partcipants of this study were current worlers who had the capacity to work, they might be relatively healthier than the general population. Furtermore, compared to the general poulation, the propotaion of men meight be higher becaouse more men than women tend to became workers in Japases society.

 

(Comment 3)

the discussion also needs to be reviewed in light of the relationship between weight and BMI as well as height

→ Thank you for valuable comment. According to this valuable comment, I rechecked influence on weight and BMI on present results. As described above, the influence of weight and BMI is slightly on present results. But as added in introduction section, Participants with short stature might have lower productivity of hematopoietic stem cell and higher activity of low grades inflammation. Since we already describe about the inflammation in discussion section, we added following sentence that explain the influence of productivity of hematopoietic stem cell on present results.

Low productivity of hematopoietic stem cell known as CD34-posistive cell also might underlying the association between hypertension and height loss. Previous our follow-up study of 363 Japanese men aged 60-69 years over 2 years revealed significant inverse association between circulating CD34-positive cell count and height loss [18]. CD34-positive cells contribute to the development of angiogenesis [19]. Since development of angiogenesis should have a beneficial influence on preventing hypertension by reducing peripheral vascular resistance, participants with shortage of circulating CD34-postive cell increase the risk of hypertension [20]. Inadequate angiogenesis related to lower adaptability to hypoxia might play an important role in the development of intervertebral disc degeneration [22-23] and osteoporosis [24].

 

 

 

Author Response File: Author Response.pdf

Reviewer 2 Report

   In the retrospective study, Shimizu and his colleague reported that height is inversely associated with incident hypertension for men but not for women, with a novel finding that baseline hypertension is significantly positively associated with height loss for men but not for women, in Japanese population.

      It is an interesting topic and the study itself was well designed.

1.       It is unclear how the height loss was defined. A related reference should be cited to clarify

2.       Between controlled hypertension and uncontrolled hypertension population, is there any difference of height loss?

 

3.       The potential mechanism how baseline hypertension is significantly positively associated with height loss for men should be discussed.

Author Response

Reviewer 2

 

Thank you for your valuable comment. A made reply for those valuable comments.

 

(Comment 1)

It is unclear how the height loss was defined. A related reference should be cited to clarify

→ Thank you for valuable comment. According to this valuable comment, added the reference of previous study that used same definition for height loss.

 

Height loss was defined as being the highest quintile of annual height decrease (>2.015 mm/year for men and >1.756 mm/year for women) as our previous study [8].

 

(Comment 2)

Between controlled hypertension and uncontrolled hypertension population, is there any difference of height loss?

→ Thank you for valuable comment. According to this valuable comment, we re-checked our study design. To evaluate the uncontrolled hypertension on height loss, we could use same study population on present study. The odds ratio and 95% confidence interval of height loss for uncontrolled hypertension were 1.30(1.15, 1.47) for men and 0.91(0.68, 1.22) for women, respectively. This is a natural result from present study. Then, this is nothing newly knowledge from present result. And to evaluate the association between controlled hypertension and height loss, present study population could not use because analysis among present study population emphasize the influence of uncontrolled hypertension. Therefore, to evaluate the influence of controlled hypertension on height loss, the target population should be limited to participants within normal range of blood pressure; systolic blood pressure<140mmHg and diastolic blood pressure<90 mmHg. Therefore, in present study, we could not compare the influence of height loss between controlled hypertension and uncontrolled hypertension. Regards with those severe limitations, we also evaluated the association between height loss and controlled hypertension. And by using the age adjusted model, the odds ratios and 95% confidence intervals were 1.06(0.83, 1.35) for men and 0.98(0.62, 1.57) for women. Those results were difficult to evaluate. Even no significant association was observed, the number of target population much smaller than total population. Then sample size itself could influence on present result. Then we did not evaluate those associations in present study.

 

 

(Comment 3)

The potential mechanism how baseline hypertension is significantly positively associated with height loss for men should be discussed.

→ Thank you for valuable comment. According to this valuable comment, we re-checked our hypothesis of present study. Previously we reported the potential mechanism that might underlying the association between height and hypertension. We thought low grade inflammation, low productivity of hematopoietic stem cell, and genetic factor might act as a determinant of the association between height and hypertension. Then I added the following sentences in Introduction section.

 

Presence of low grade chronic inflammation, productivity of hematopoietic stem cells, and genetic factors are potential candidates that explain the inverse association between height and hypertension [4,5].

 

And we already discussed about the oxidative stress that induce inflammation in discussion section. As following.

Inflammation is a potential underlying biochemical mechanism that explains the results of the present study. Aging is a process that increases oxidative stress. Oxidative stress causes hypertension and activates inflammation [15]. Since the inflammatory response contributes to the onset of intervertebral disk degeneration [16] and vertebral fractures [17], hypertension could act a risk factor for height loss by indicating inflammatory activity associated with intervertebral disk degeneration and vertebral fractures.

However, we did not mentioned about the low productivity of hematopoietic stem cell. Then we added following sentences in discussion section.

Low productivity of hematopoietic stem cell known as CD34-posistive cell also might underlying the association between hypertension and height loss. Previous our follow-up study of 363 Japanese men aged 60-69 years over 2 years revealed significant inverse association between circulating CD34-positive cell count and height loss [18]. CD34-positive cells contribute to the development of angiogenesis [19]. Since development of angiogenesis should have a beneficial influence on preventing hypertension by reducing peripheral vascular resistance, participants with shortage of circulating CD34-postive cell increase the risk of hypertension [20]. Inadequate angiogenesis related to lower adaptability to hypoxia might play an important role in the development of intervertebral disc degeneration [22-23] and osteoporosis [24].

And for genetic fators, we added the following sentences in limitation section.

Because there are many unknown genetic factors that influence angiogenesis and inflammation, further investigation is necessary.

 

The reason why sex difference association was observed in present study is already discussed in discussion section. Those were sample size problem and the difference in causes of height loss.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The manuscript is ok for publication, the authors made all required changes.