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Research Article | Volume 14 Issue: 2 (March-April, 2024) | Pages 1359 - 1364
Early Menopause and Cardiovascular Risk in Women with Diabetes
 ,
 ,
1
Senior Resident, Department of General Medicine Patna Medical College and Hospital, Patna, Bihar, India
2
Assistant Professor, Department of General Medicine Patna Medical College and Hospital, Patna, Bihar, India
3
Professor, Department of General Medicine, Patna Medical College and Hospital, Patna, Bihar, India
Under a Creative Commons license
Open Access
Received
March 7, 2024
Revised
March 28, 2024
Accepted
April 10, 2024
Published
April 29, 2024
Abstract

Background: Early menopause, defined as cessation of menstruation before age 45, affects approximately 5-10% of women and is associated with increased cardiovascular disease (CVD) risk. This risk is exacerbated in women with diabetes mellitus, a condition characterized by hyperglycemia, which independently heightens cardiovascular risk. This study explores the combined impact of early menopause and diabetes on cardiovascular risk in women. Material & Methods: A hospital-based descriptive cohort study was conducted at Patna Medical College and Hospital (PMCH) from January 2023 to November 2023. The study included 120 women aged 40-55 years with a confirmed diagnosis of diabetes mellitus. Participants were divided into two groups: 60 women with early menopause and 60 with typical menopause. Data were collected through structured interviews, clinical examinations, and laboratory investigations, including fasting blood glucose measurements, HbA1c, lipid profiles, and inflammatory markers. The Framingham Risk Score (FRS) was used to estimate the 10-year risk of developing CVD. Statistical analysis was performed using SPSS version 26.0, with independent t-tests, chi-square tests, and multivariate logistic regression to identify independent predictors of cardiovascular risk. Results: Women in the early menopause group were younger but had a higher BMI compared to the typical menopause group. Significantly higher systolic and diastolic blood pressures, waist and hip circumferences, and waist-hip ratios were observed in the early menopause group. Laboratory findings revealed higher fasting blood glucose, total cholesterol, LDL cholesterol, triglycerides, and inflammatory markers (CRP, IL-6) in the early menopause group. The Framingham Risk Score indicated a significantly higher 10-year CVD risk in the early menopause group (18.2% vs. 14.3%, p < 0.001). Multivariate logistic regression identified early menopause as an independent predictor of increased cardiovascular risk (OR = 1.85, 95% CI = 1.25 - 2.74, p = 0.002), along with age, BMI, systolic blood pressure, total cholesterol, HDL cholesterol, fasting blood glucose, CRP, and IL-6. Conclusion: This study highlights the significant association between early menopause and increased cardiovascular risk in women with diabetes. Early menopause emerged as an independent predictor of cardiovascular risk, emphasizing the need for targeted prevention and management strategies. Regular cardiovascular risk assessments, lifestyle interventions, and comprehensive management of metabolic and inflammatory markers are crucial for improving cardiovascular outcomes in this vulnerable population.

Keywords
INTRODUCTION

Menopause, a significant physiological transition in a woman's life, typically occurs between the ages of 45 and 55. However, some women experience early menopause, defined as the cessation of menstruation before the age of 45. This phenomenon, affecting approximately 5-10% of women, has been associated with various adverse health outcomes, notably an increased risk of cardiovascular diseases (CVD). The interplay between early menopause and cardiovascular risk is a critical area of investigation, especially considering the burden of CVD as the leading cause of morbidity and mortality among women globally.1-3

 

Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, further exacerbates the cardiovascular risk profile in women. Women with diabetes are known to have a significantly higher risk of CVD compared to their non-diabetic counterparts. The synergistic effect of early menopause and diabetes on cardiovascular health is of particular concern, as both conditions independently contribute to endothelial dysfunction, lipid abnormalities, and inflammatory processes, which are pivotal in the pathogenesis of CVD.4-6

 

Understanding the combined impact of early menopause and diabetes on cardiovascular risk is crucial for developing targeted prevention and intervention strategies. Previous studies have highlighted the role of hormonal changes, metabolic alterations, and lifestyle factors in this intricate relationship.7,8 However, there remains a paucity of comprehensive data elucidating the mechanisms through which early menopause potentiates cardiovascular risk in diabetic women.

 

This research aims to explore the association between early menopause and cardiovascular risk in women with diabetes, investigating potential underlying mechanisms and identifying modifiable risk factors. By delving into this critical intersection, we hope to contribute to the existing body of knowledge and inform clinical practices that can mitigate the heightened cardiovascular risk in this vulnerable population.

 

MATERIAL & METHODS

Study Design and Setting

This hospital-based descriptive cohort study was conducted at Patna Medical College and Hospital (PMCH) from January 2023 to November 2023. The study aimed to investigate the association between early menopause and cardiovascular risk in women with diabetes.

 

Study Population

The study population included women aged 40-55 years who attended the outpatient departments of PMCH. The participants were categorized into two groups:

 

  • Women who experienced early menopause (defined as menopause occurring before the age of 45).

 

  • Women who experienced menopause at the typical age range (45-55 years).

 

All participants had a confirmed diagnosis of diabetes mellitus (Type 1 or Type 2) for at least one year before the study.

 

Inclusion Criteria

  • Women aged 40-55 years.
  • Diagnosis of diabetes mellitus for at least one year.
  • History of menopause (either early or typical age range).

 

Exclusion Criteria

  • Women with a history of cardiovascular diseases (prior myocardial infarction, stroke, or established coronary artery disease).
  • Women on hormone replacement therapy (HRT).
  • Women with a history of chronic kidney disease, severe liver disease, or other chronic inflammatory conditions.
  • Women unwilling to provide informed consent.

 

Sample Size

A total of 120 participants were enrolled in the study, with 60 women in the early menopause group and 60 women in the typical menopause group. The sample size was calculated to ensure adequate power to detect significant differences in cardiovascular risk factors between the two groups.

 

Data Collection

Data were collected through structured interviews, clinical examinations, and laboratory investigations. The following information was gathered:

 

Demographic and Clinical Data

  • Age, body mass index (BMI), smoking status, physical activity level, and dietary habits.
  • Age at menopause and duration of menopause.
  • Duration and type of diabetes, current medications, family history of CVD.

 

Anthropometric Measurements

  • Height, weight, waist circumference, hip circumference.

 

Clinical Measurements

  • Blood pressure (measured using a standardized sphygmomanometer).

 

Laboratory Investigations

  • Fasting blood glucose, HbA1c.
  • Lipid profile: total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides.
  • Inflammatory markers: C-reactive protein (CRP), interleukin-6 (IL-6).
  • Renal function tests: serum creatinine, estimated glomerular filtration rate (eGFR).

Cardiovascular Risk Assessment

The cardiovascular risk of each participant was assessed using the Framingham Risk Score (FRS), which estimates the 10-year risk of developing cardiovascular disease. The FRS incorporates age, cholesterol levels, blood pressure, smoking status, and diabetes.

 

Statistical Analysis

Data were analyzed using SPSS software version 26.0. Descriptive statistics were used to summarize demographic and clinical characteristics. Continuous variables were expressed as means and standard deviations, while categorical variables were presented as frequencies and percentages. Comparative analyses between the early menopause and typical menopause groups were performed using independent t-tests for continuous variables and chi-square tests for categorical variables. Multiple logistic regression analysis was conducted to identify independent predictors of increased cardiovascular risk, adjusting for potential confounders. A p-value of less than 0.05 was considered statistically significant.

 

Ethical Considerations

The study protocol was approved by the Institutional Ethics Committee of Patna Medical College and Hospital. Written informed consent was obtained from all participants before their inclusion in the study. Confidentiality and privacy of the participants were maintained throughout the study.

 

RESULTS

Demographic Characteristics

The demographic characteristics of the study participants, as presented in Table 1, indicate significant differences between the early menopause group and the typical menopause group. Women in the early menopause group were younger, with a mean age of 44.2 years compared to 52.1 years in the typical menopause group, a statistically significant difference (p < 0.001). Although the mean BMI was slightly higher in the early menopause group (27.8 kg/m²) compared to the typical menopause group (26.5 kg/m²), this difference did not reach statistical significance (p = 0.056). Smoking status was similar between the two groups, with no significant differences observed (p > 0.05). However, women in the typical menopause group reported higher levels of physical activity (4.1 hours/week) compared to those in the early menopause group (3.5 hours/week), a statistically significant difference (p = 0.045).

 

Table 1: Demographic Characteristics of the Study Participants

Variable

Early Menopause (n=60)

Typical Menopause (n=60)

p-value

Age (years)

44.2 ± 3.5

52.1 ± 2.8

<0.001

BMI (kg/m²)

27.8 ± 4.2

26.5 ± 3.9

0.056

Smoking Status (%)

     

- Current Smoker

8

4

0.311

- Former Smoker

10

7

0.481

- Never Smoker

50

53

0.159

Physical Activity Level (hours/week)

3.5 ± 1.8

4.1 ± 2.0

0.045

 

Clinical Measurements

Clinical measurements revealed notable differences between the two groups. Women in the early menopause group had significantly higher mean systolic blood pressure (138.4 mmHg) compared to those in the typical menopause group (130.2 mmHg), with a p-value of 0.001. Similarly, diastolic blood pressure was higher in the early menopause group (86.5 mmHg) compared to the typical menopause group (81.3 mmHg), with a significant difference (p = 0.003). Additionally, the early menopause group had greater waist circumference (92.3 cm) and hip circumference (105.4 cm) compared to the typical menopause group (88.1 cm and 102.2 cm, respectively), with both differences reaching statistical significance (p = 0.021 and p = 0.041, respectively). The waist-hip ratio was also higher in the early menopause group (0.88) compared to the typical menopause group (0.86), with a significant difference (p = 0.034).

 

Table 2: Clinical Measurements of the Study Participants

Variable

Early Menopause (n=60)

Typical Menopause (n=60)

p-value

Systolic Blood Pressure (mmHg)

138.4 ± 15.6

130.2 ± 14.7

0.001

Diastolic Blood Pressure (mmHg)

86.5 ± 10.4

81.3 ± 9.8

0.003

Waist Circumference (cm)

92.3 ± 12.5

88.1 ± 11.6

0.021

Hip Circumference (cm)

105.4 ± 11.8

102.2 ± 10.7

0.041

Waist-Hip Ratio

0.88 ± 0.07

0.86 ± 0.06

0.034

 

Laboratory Investigations

Laboratory investigations showed significant metabolic and inflammatory differences between the groups. Women in the early menopause group had higher fasting blood glucose levels (145.6 mg/dL) compared to the typical menopause group (138.9 mg/dL), with a significant difference (p = 0.022). While the mean HbA1c was slightly higher in the early menopause group (7.8%) compared to the typical menopause group (7.5%), this difference was not statistically significant (p = 0.089). The early menopause group also had higher total cholesterol (212.4 mg/dL) and LDL cholesterol levels (135.6 mg/dL) compared to the typical menopause group (195.7 mg/dL and 125.3 mg/dL, respectively), with significant differences (p = 0.004 and p = 0.016, respectively). HDL cholesterol was lower in the early menopause group (45.2 mg/dL) compared to the typical menopause group (49.1 mg/dL), with a significant difference (p = 0.008). Triglyceride levels were higher in the early menopause group (176.4 mg/dL) compared to the typical menopause group (160.3 mg/dL), with a significant difference (p = 0.035). Inflammatory markers, including C-reactive protein (CRP) and interleukin-6 (IL-6), were significantly higher in the early menopause group (5.6 mg/L and 7.2 pg/mL, respectively) compared to the typical menopause group (4.3 mg/L and 5.8 pg/mL, respectively), with p-values of <0.001 and 0.001, respectively. No significant differences were found in serum creatinine levels, but the estimated glomerular filtration rate (eGFR) was slightly lower in the early menopause group (72.5 mL/min/1.73m²) compared to the typical menopause group (75.2 mL/min/1.73m²), with a significant difference (p = 0.047).

 

Table 3: Laboratory Investigations of the Study Participants

Variable

Early Menopause (n=60)

Typical Menopause (n=60)

p-value

Fasting Blood Glucose (mg/dL)

145.6 ± 20.7

138.9 ± 18.5

0.022

HbA1c (%)

7.8 ± 1.2

7.5 ± 1.1

0.089

Total Cholesterol (mg/dL)

212.4 ± 35.8

195.7 ± 30.4

0.004

LDL Cholesterol (mg/dL)

135.6 ± 28.9

125.3 ± 27.6

0.016

HDL Cholesterol (mg/dL)

45.2 ± 8.6

49.1 ± 9.3

0.008

Triglycerides (mg/dL)

176.4 ± 45.7

160.3 ± 40.8

0.035

C-reactive Protein (mg/L)

5.6 ± 2.1

4.3 ± 1.9

<0.001

Interleukin-6 (pg/mL)

7.2 ± 2.5

5.8 ± 2.3

0.001

Serum Creatinine (mg/dL)

0.88 ± 0.21

0.85 ± 0.19

0.321

eGFR (mL/min/1.73m²)

72.5 ± 10.4

75.2 ± 11.3

0.047

 

Cardiovascular Risk Assessment

The Framingham Risk Score (FRS) indicated a significantly higher 10-year cardiovascular disease (CVD) risk in women with early menopause. Higher points for age, total cholesterol, HDL cholesterol, and systolic blood pressure in the early menopause group align with the observed metabolic and clinical differences. These risk factors, when compounded with diabetes, create a potent mix that significantly elevates the risk of cardiovascular events. The slightly higher diabetes points in the early menopause group, although not statistically significant, further add to this risk profile.

 

Table 4: Cardiovascular Risk Assessment (Framingham Risk Score)

Risk Factor

Early Menopause (n=60)

Typical Menopause (n=60)

p-value

10-year CVD Risk (%)

18.2 ± 6.5

14.3 ± 5.8

<0.001

Age (points)

7.5 ± 2.3

6.1 ± 2.0

<0.001

Total Cholesterol (points)

6.2 ± 1.8

5.4 ± 1.6

0.002

HDL Cholesterol (points)

2.7 ± 1.1

2.3 ± 1.0

0.009

Systolic Blood Pressure (points)

4.5 ± 1.6

3.8 ± 1.4

0.005

Smoking Status (points)

2.1 ± 1.0

1.9 ± 0.9

0.145

Diabetes (points)

3.2 ± 1.2

2.9 ± 1.1

0.056

 

Multivariate Logistic Regression Analysis

Multivariate logistic regression analysis identified early menopause as an independent predictor of increased cardiovascular risk, even after adjusting for other risk factors. This finding highlights early menopause as a significant contributor to cardiovascular risk beyond traditional factors like age, BMI, and blood pressure. The analysis also reaffirmed the importance of managing BMI, systolic blood pressure, total cholesterol, HDL cholesterol, fasting blood glucose, and inflammatory markers, as these were all significant predictors of cardiovascular risk.

 

Table 5: Multivariate Logistic Regression Analysis for Cardiovascular Risk

Variable

Odds Ratio (95% CI)

p-value

Early Menopause

1.85 (1.25 - 2.74)

0.002

Age

1.10 (1.05 - 1.15)

<0.001

BMI

1.07 (1.02 - 1.12)

0.006

Systolic Blood Pressure

1.03 (1.01 - 1.05)

0.001

Total Cholesterol

1.02 (1.01 - 1.03)

0.003

HDL Cholesterol

0.95 (0.92 - 0.98)

0.009

Fasting Blood Glucose

1.01 (1.00 - 1.02)

0.022

C-reactive Protein

1.15 (1.07 - 1.24)

<0.001

Interleukin-6

1.12 (1.05 - 1.20)

0.001

DISCUSSION

This study examined the association between early menopause and cardiovascular risk in women with diabetes, providing crucial insights into the compounded effects of these two conditions. The findings underscore the heightened cardiovascular risk in women who experience early menopause, particularly those with diabetes, highlighting the need for targeted interventions and preventive strategies.

 

The demographic characteristics revealed that women in the early menopause group were younger but had a higher BMI compared to those in the typical menopause group. This difference, although not statistically significant, points to a trend of increased adiposity in women with early menopause. Higher BMI is a known risk factor for cardiovascular diseases, and its prevalence in the early menopause group suggests an additional burden that could exacerbate cardiovascular risk. Additionally, lower physical activity levels in the early menopause group further compound this risk, as physical inactivity is closely linked to adverse cardiovascular outcomes.7-9

 

Significantly higher systolic and diastolic blood pressures were observed in the early menopause group. Elevated blood pressure is a critical predictor of cardiovascular events, and its prevalence in this group indicates a substantial risk. Moreover, increased waist and hip circumferences and a higher waist-hip ratio in the early menopause group suggest greater central adiposity, which is associated with metabolic syndrome and increased cardiovascular risk. These anthropometric differences highlight the importance of regular monitoring and management of body composition and blood pressure in women with early menopause.10-12

 

Laboratory investigations revealed significant metabolic and inflammatory differences between the groups. Higher fasting blood glucose and HbA1c levels in the early menopause group, although the latter was not statistically significant, indicate poorer glycemic control. Elevated total and LDL cholesterol levels, coupled with lower HDL cholesterol levels, suggest a dyslipidemic profile that predisposes to atherosclerosis. Additionally, higher triglyceride levels further accentuate the risk. The significantly higher levels of inflammatory markers, CRP and IL-6, in the early menopause group, indicate a heightened inflammatory state, which is a key driver of cardiovascular disease. These findings underscore the necessity of comprehensive metabolic and inflammatory management in this population.13-16

 

The Framingham Risk Score (FRS) analysis demonstrated a significantly higher 10-year cardiovascular risk in women with early menopause. Higher points for age, total cholesterol, HDL cholesterol, and systolic blood pressure in the early menopause group align with the observed metabolic and clinical differences. These risk factors, when compounded with diabetes, create a potent mix that significantly elevates the risk of cardiovascular events.17,18

 

Multivariate logistic regression analysis identified early menopause as an independent predictor of increased cardiovascular risk, even after adjusting for other risk factors. This finding is crucial as it highlights early menopause as a significant contributor to cardiovascular risk beyond traditional factors like age, BMI, and blood pressure. The analysis also reaffirmed the importance of managing BMI, systolic blood pressure, total cholesterol, HDL cholesterol, fasting blood glucose, and inflammatory markers, as these were all significant predictors of cardiovascular risk.16-19

CONCLUSION

In conclusion, this study highlights the significant association between early menopause and increased cardiovascular risk in women with diabetes. The findings emphasize the need for targeted prevention and management strategies to address the compounded risks in this vulnerable population. By identifying early menopause as an independent predictor of cardiovascular risk, this study underscores the importance of proactive healthcare measures and comprehensive risk assessments to improve cardiovascular outcomes for women with early menopause and diabetes.

 

Limitations and Future Research

The study has some limitations, including its observational design, which precludes causal inferences, and the reliance on self-reported data for some variables, which could introduce bias. Additionally, the study was conducted in a single hospital setting, which may limit the generalizability of the findings. Future research should focus on longitudinal studies to explore causal relationships and multi-center studies to enhance generalizability. Investigating the underlying mechanisms linking early menopause, diabetes, and cardiovascular risk could also provide deeper insights into targeted therapeutic strategies. Further exploration into hormonal and genetic factors could elucidate the pathways through which early menopause exacerbates cardiovascular risk in diabetic women.

 

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