Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Sample
2.2. Bioethics
2.3. SMI Calculation
2.4. Other Baseline Measurements
2.5. Endpoint and Follow-up Evaluation
2.6. Statistical Analysis
3. Results
4. Discussion
Limitations and Strengths
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Baseline Characteristics | Skeletal Muscle Mass Index Tertiles | |||
---|---|---|---|---|
1st Tertile | 2nd Tertile | 3rd Tertile | p-Value | |
N | 371 | 374 | 396 | |
Sociodemographic factors | ||||
Age, years | 64 (12) | 64 (13) | 63 (14) | 0.22 |
Male sex, % | 46 | 46 | 47 | 0.97 |
Anthropometric factors | ||||
Body mass index, kg/m2 | 23.9 (2.1) | 28.0 (1.5) | 33.6 (3.7) | <0.001 |
Waist circumference, cm | 91 (11) | 101 (9) | 111 (11) | <0.001 |
Waist-to-hip ratio | 0.91 (0.09) | 0.95 (0.09) | 0.97 (0.09) | <0.001 |
Lifestyle factors | ||||
Physical inactivity, % | 30 | 38 | 35 | 0.93 |
MedDietScore, range 0–55 | 34.4 (0.6) | 34.5 (0.6) | 34.3 (0.6) | 0.04 |
Weekly alcohol consumption, % | 61 | 62 | 63 | 0.81 |
Current smoking, % | 23 | 30 | 38 | <0.001 |
Clinical factors | ||||
History of hypertension, % | 30 | 44 | 53 | <0.001 |
History of diabetes mellitus, % | 22 | 17 | 85 | <0.001 |
History of hypercholesterolemia, % | 33 | 36 | 44 | 0.00 |
Metabolic syndrome, % | 16 | 39 | 55 | <0.001 |
Family CVD history, % | 40 | 37 | 40 | 0.70 |
Inflammation/coagulation markers | ||||
Ultra-sensitive C-Reactive Protein, mg/L | 3.4 (3.9) | 1.8 (2.1) | 3.0 (3.2) | <0.001 |
Interleukin 6, pg/dL | 3.8 (11.5) | 4.4 (13.0) | 4.7 (24.0) | 0.87 |
Tumor necrosis factor-alpha, pg/mL | 1.51 (0.50) | 1.53 (0.50) | 1.62 (0.49) | 0.63 |
White blood cells, 103 counts | 6.4 (1.6) | 5.9 (1.5) | 6.2 (1.4) | <0.001 |
Aortic stiffness markers | ||||
Aortic distensibility, 1000*mmHg−1 | 1.55 (1.47) | 1.70 (1.07) | 1.67 (1.46) | <0.001 |
Pulmonary pressure, mmHg | 31 (6) | 31 (6) | 30 (6) | 0.02 |
Liver function markers | ||||
Alanine transaminase, U/L | 14.8 (6.8) | 15.9 (7.1) | 18.3 (10.4) | <0.001 |
Aspartate transaminase, U/L | 22.7 (7.9) | 22.6 (11.4) | 22.0 (6.4) | 0.45 |
Glucose/insulin homeostasis markers | ||||
Fasting glucose, mg/dL | 96 (23) | 104 (31) | 107 (28) | <0.001 |
HOMA-IR | 0.81 (0.67) | 1.04 (1.44) | 1.80 (3.04) | <0.001 |
Lipid markers | ||||
Total cholesterol, mg/dL | 205 (39) | 205 (40) | 204 (42) | 0.97 |
High density lipoprotein cholesterol, mg/dL | 45 (10) | 46 (9) | 50 (13) | <0.001 |
Triglycerides, mg/dL | 127 (85) | 147 (95) | 160 (91) | <0.001 |
Low density lipoprotein cholesterol, mg/dL | 128 (34) | 129 (34) | 129 (33) | 0.89 |
Hormones | ||||
Total testosterone, ng/dL | 157 (19) | 177 (20) | 220 (242) | 0.05 |
4-year follow-up measurements | ||||
First fatal/non-fatal cardiovascular disease incidence | 19.2 | 14.2 | 13.3 | 0.04 |
First fatal/non-fatal cardiovascular disease incidence (excluding participants <65 years old) | 27.4 | 23.9 | 25.9 | 0.01 |
Woman-to-man cardiovascular disease incidence ratio | 0.68 | 0.57 | 0.78 | 0.03 |
Woman-to-man cardiovascular disease incidence ratio (excluding participants <65 years old) | 0.88 | 0.60 | 0.77 | 0.001 |
Models | Model 1 | Model 2 | Model 3 | Model 4 | Model 5 | Model 6 | Model 7 | Model 8 | Model 9 |
---|---|---|---|---|---|---|---|---|---|
HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | |
SMI tertiles | |||||||||
1st | Ref | ref | ref | ref | Ref | ref | ref | ref | ref |
2nd | 0.76 (0.43, 0.91) | 0.82 (0.52, 0.91) | 0.85 (0.52, 0.93) | 0.86 (0.40, 0.93) | 0.87 (0.45, 0.99) | 0.92 (0.52, 1.08) | 1.28 (0.61, 2.65) | 1.01 (0.52, 1.92) | 1.09 (0.51, 2.32) |
3rd | 0.70 (0.36, 0.86) | 0.74 (0.43, 0.86) | 0.75 (0.45, 0.82) | 0.78 (0.48, 0.85) | 0.83 (0.37, 0.95) | 0.89 (0.41, 0.99) | 1.31 (0.55, 3.12) | 0.83 (0.37, 1.88) | 0.99 (0.39, 2.48) |
Age, per 1 year | - | 1.04 (1.02, 1.06) | 1.04 (1.03, 1.06) | 1.06 (1.03, 1.08) | 1.04 (1.02, 1.06) | 1.07 (1.00, 1.13) | 1.06 (1.02, 1.10) | 1.04 (1.02, 1.07) | 1.05 (1.01, 1.10) |
Male sex | - | 1.74 (1.16, 2.59) | 1.75 (1.15, 2.67) | 1.76 (1.13, 2.74) | 2.10 (1.22, 3.59) | 1.99 (0.91, 4.33) | 1.70 (1.91, 3.17) | 2.41 (1.40, 4.15) | 1.80 (0.65, 5.01) |
Waist circumference, per 1 cm | - | - | 0.99 (0.97, 1.01) | 0.99 (0.97, 1.01) | 0.99 (0.97, 1.01) | 1.00 (0.95, 1.04) | 0.99 (0.96, 1.02) | 0.99 (0.96, 1.02) | 0.99 (0.96, 1.03) |
Current smoking, y/n | - | - | - | 1.15 (0.69, 1.93) | 1.15 (0.69, 1.93) | 1.15 (0.69, 1.93) | 1.33 (0.63, 2.81) | 0.99 (0.53, 1.85) | 1.07 (0.48, 2.39) |
Physical activity, y/n | - | - | - | 0.87 (0.65, 1.23) | 0.87 (0.65, 1.23) | 0.87 (0.65, 1.23) | 0.99 (0.71, 2.14) | 0.97 (0.73, 1.31) | 0.89 (0.68, 1.31) |
MedDietScore, per 1 unit (0–55) | - | - | - | 0.96 (0.94, 1.02) | 0.96 (0.94, 1.02) | 0.96 (0.94, 1.02) | 0.99 (0.96, 1.05) | 0.97 (0.94, 1.02) | 0.96 (0.94, 1.02) |
Diabetes mellitus, y/n | - | - | - | - | 1.81 (0.93, 3.52) | 2.12 (0.84, 5.33) | 1.55 (0.78, 3.07) | 1.71 (0.32, 3.18) | 1.44 (0.69, 3.01) |
Hypertension, y/n | - | - | - | - | 1.31 (0.75, 2.29) | 1.34 (0.51, 3.17) | 1.01 (0.53, 1.92) | 1.41 (0.81, 2.47) | 1.34 (0.67, 2.68) |
Family history of CVD, y/n | - | - | - | - | 1.55 (0.61, 1.79) | 1.57 (0.72, 3.45) | 1.34 (0.74, 2.42) | 1.01 (0.60, 1.70) | 1.19 (0.64, 2.21) |
HDL-C, per 1 mg/dL | - | - | - | - | 0.97 (0.95, 1.01) | 1.03 (0.95, 1.05) | 1.03 (0.96, 1.06) | 1.02 (0.99, 1.04) | 1.02 (0.99, 1.06) |
TGL, per 1 mg/dL | - | - | - | - | 0.99 (0.98, 1.01) | 1.01 (0.99, 1.02) | 1.01 (0.99, 1.02) | 1.00 (0.99, 1.01) | 1.01 (0.99, 1.02) |
HOMA-IR, per 1 unit | - | - | - | - | - | 1.12 (1.02, 1.22) | - | - | - |
usCRP, per 1 mg/L | - | - | - | - | - | 1.04 (1.02, 1.11) | - | - | |
White blood cells, per 1 count | - | - | - | - | - | - | 1.20 (1.01, 1.48) | - | - |
Arterial distensibility, per 1000 mmHg−1 | - | - | - | - | - | - | - | 0.90 (0.74, 0.96) | - |
Total testosterone, per 1 ng/dL | - | - | - | - | - | - | - | - | 0.99 (0.97, 1.01) |
Models | Standard Model | Standard Model Plus HOMA-IR | Standard Model Plus usCRP and WBC | Standard Model Plus Arterial Distensibility | Standard Model Plus Total Testosterone |
---|---|---|---|---|---|
HR (95%CI) | HR (95%CI) | HR (95%CI) | HR (95%CI) | HR (95%CI) | |
Total sample excluding participants with age <65 years | |||||
2nd vs. 1st SMI tertile | 0.80 (0.45, 0.96) | 0.95 (0.36, 1.31) | 1.03 (0.59, 1.56) | 0.92 (0.45, 1.38) | 1.07 (0.52, 1.42) |
3rd vs. 1st SMI tertile | 1.20 (0.61, 2.35) | 1.15 (0.53, 2.53) | 1.29 (0.55, 3.06) | 1.33 (0.53, 3.38) | 1.13 (0.42, 2.71) |
p for age interaction = 0.003 | |||||
Men | |||||
2nd vs. 1st SMI tertile | 0.87 (0.56, 1.85) | 0.94 (0.30, 1.93) | 0.87 (0.30, 2.54) | 1.04 (0.43, 2.15) | 0.88 (0.29, 2.62) |
3rd vs. 1st SMI tertile | 0.64 (0.36, 0.99) | 0.74 (0.41, 0.98) | 0.58 (0.13, 0.89) | 0.84 (0.54, 1.42) | 0.59 (0.25, 1.55) |
Women | |||||
2nd vs. 1st SMI tertile | 0.71 (0.33, 0.95) | 1.10 (0.34, 1.99) | 1.12 (0.36, 3.45) | 0.75 (0.19, 1.71) | 0.79 (0.40, 0.99) |
3rd vs. 1st SMI tertile | 1.42 (0.50, 4.03) | 1.10 (0.23, 4.31) | 1.91 (0.51, 4.66) | 1.52 (0.47, 4.91) | 1.89 (0.46, 4.76) |
p for gender interaction = 0.01 | |||||
Men excluding participants with age < 65 years | |||||
2nd vs. 1st SMI tertile | 0.92 (0.40, 1.07) | 1.03 (0.22, 1.89) | 1.21 (0.40, 3.71) | 1.19 (0.38, 3.80) | 0.99 (0.29, 1.35) |
3rd vs. 1st SMI tertile | 0.69 (0.51, 1.10) | 0.73 (0.65, 1.19) | 0.74 (0.46, 1.21) | 0.70 (0.51, 1.09) | 0.75 (0.42, 1.16) |
Women excluding participants with age < 65 years | |||||
2nd vs. 1st SMI tertile | 0.59 (0.19, 0.89) | 0.58 (0.14, 0.86) | 0.89 (0.36, 1.50) | 0.63 (0.17, 1.09) | 0.53 (0.14, 1.05) |
3rd vs. 1st SMI tertile | 1.15 (0.45, 3.93) | 1.29 (0.67, 4.01) | 1.33 (0.68, 3.20) | 1.36 (0.46, 3.98) | 0.91 (0.30, 2.17) |
p for gender and age interaction = 0.004 |
Total Sample | |||
---|---|---|---|
Total | Men | Women | |
N | 1141 | 529 | 612 |
Beta-Coefficient (standard error) | Beta-Coefficient (standard error) | Beta-Coefficient (standard error) | |
usCRP, per 1 mg/L | −0.22 (0.13) | −0.27 (0.13) | −0.31 (0.13) |
Interleukin 6, per 1 pg/dL | +0.11 (0.21) | −0.10 (0.19) | −0.12 (0.20) |
Tumor necrosis factor-alpha, per 1 pg/mL | +0.19 (1.18) | −0.17 (1.68) | −0.18 (0.91) |
White blood cells, per 103 counts | −0.32 (0.09) | −0.19 (0.11) | −0.25 (0.12) |
HOMA-IR, per 1 unit | −0.67 (0.21) | −0.54 (0.71) | −0.81 (0.24) |
Arterial distensibility, per 1000 mmHg−1 | −0.40 (0.89) | −0.61 (0.90) | −0.33 (0.77) |
Total testosterone, per 1 ng/dL | +0.19 (0.11) | +0.27 (0.16) | +0.08 (0.10) |
Total sample excluding participants <65 years old | |||
Total | Men | Women | |
N | 670 | 327 | 343 |
usCRP, per 1 mg/L | −0.21 (0.12) | −0.15 (0.11) | −0.38 (0.15) |
Interleukin 6, per 1 pg/dL | +0.12 (0.22) | −0.09 (0.17) | −0.13 (0.21) |
Tumor necrosis factor-alpha, per 1 pg/mL | +0.20 (1.17) | −0.14 (1.60) | −0.17 (0.90) |
White blood cells, per 103 counts | −0.19 (0.25) | −0.18 (0.15) | −0.26 (0.16) |
HOMA-IR, per 1 unit | −0.25 (0.24) | −0.25 (0.60) | −0.29 (0.27) |
Arterial distensibility, per 1000 mmHg−1 | −0.51 (0.92) | −0.64 (0.87) | −0.45 (0.82) |
Total testosterone, per 1 ng/dL | +0.23 (0.12) | +0.14 (0.13) | +0.19 (0.11) |
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Chrysohoou, C.; Kouvari, M.; Lazaros, G.; Varlas, J.; Dimitriadis, K.; Zaromytidou, M.; Masoura, C.; Skoumas, J.; Kambaxis, M.; Galiatsatos, N.; et al. Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors. Nutrients 2020, 12, 3293. https://doi.org/10.3390/nu12113293
Chrysohoou C, Kouvari M, Lazaros G, Varlas J, Dimitriadis K, Zaromytidou M, Masoura C, Skoumas J, Kambaxis M, Galiatsatos N, et al. Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors. Nutrients. 2020; 12(11):3293. https://doi.org/10.3390/nu12113293
Chicago/Turabian StyleChrysohoou, Christina, Matina Kouvari, George Lazaros, John Varlas, Kyriakos Dimitriadis, Marina Zaromytidou, Constantina Masoura, John Skoumas, Manolis Kambaxis, Nikos Galiatsatos, and et al. 2020. "Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors" Nutrients 12, no. 11: 3293. https://doi.org/10.3390/nu12113293