Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

Figures & data

Table 1 Socio-demographic and clinical characteristics of older patients with hip fracture included in the study (n = 746)

Characteristic	CVD		P-value
	Yes (n = 472)	No (n = 274)
Age, years (mean ± SD)	83.0 ± 7.1	80.8 ± 9.2	0.032
Females, %	73.7	68.7	0.448
Admitted from long term RCF, %	28.7	33.7	0.386
Dementia, %	22.4	30.3	0.151
Diabetes mellitus, %	15.2	15.3	0.967
COPD, %	11.2	11.1	0.987
Parkinson’s disease, %	3.4	4.0	0.768
Current smoker, %	3.9	5.0	0.654
Ex-smoker, %	10.1	14.1	0.307
Alcohol overuser,* %	5.6	4.0	0.572
User of walking device, %	37.4	30.9	0.233
ASA score ≥ 3	79.3	57.3	0.001
Cervical HF, %	53.1	48.5	0.543
Hemoglobin < 120 g/L, %	65.4	62.6	0.745
Albumin < 33 g/L, %	25.1	34.3	0.103
eGFR < 60 mL/minute/1.73 m^2, %	48.3	37.4	0.036
eGFR < 30 mL/minute/1.73 m^2, %	5.1	5.2	1.000

Notes:

* Three or more times per week. Values in bold indicate statistically significant P values.

Abbreviations: CVD, cardiovascular disease; RCF, residential care facility; COPD, chronic obstructive pulmonary disease; HF, hip fracture; eGFR, estimated glomerular filtration rate; ASA, American Society of Anesthesiologists; SD, standard deviation.

Table 2 Parameters of mineral and bone metabolism in older hip-fracture patients with and without cardiovascular disease

	No CVD (n = 274)	Hypertension (n = 337)	CAD (n = 171)	Stroke (n = 100)	AF (n = 99)	Any CVD (n = 472)
Age, years	80.8 (9.2)	82.4 (7.3)*	83.9 (7.1)***	83.9 (6.4)***	83.8 (6.3)***	83.0 (7.1)***
25(OH)D, nmol/L	36.5 (18.9)	36.1 (17.5)	39.1 (18.1)	40.1 (20.0)	36.8 (13.3)	37.8 (18.1)
PTH, pmol/L	6.0 (4.3)	7.2 (5.1)**	9.9 (8.5)***	10.0 (7.5)***	10.3 (7.1)***	7.6 (6.2)***
Calcium, mmol/L	2.27 (0.13)	2.29 (0.13)	2.27 (0.12)	2.26 (0.10)	2.26 (0.12)	2.28 (0.13)
Phosphate, mmol/L	0.91 (0.27)	0.99 (0.26)**	1.02 (0.56)**	0.86 (0.29)	0.87 (0.34)	0.99 (0.56)*
Magnesium, mmol/L	0.77 (0.11)	0.76 (0.14)	0.81 (0.12)***	0.80 (0.19)*	0.81 (0.13)**	0.78 (0.14)
Osteocalcin, ng/mL	17.4 (16.0)	16.6 (10.6)	20.6 (22.9)	16.2 (14.5)	17.5 (13.4)	17.6 (15.2)
BAP, IU	26.3 (17.8)	26.6 (12.6)	27.6 (11.8)	26.2 (11.3)	25.5 (8.8)	26.8 (12.2)
Osteocalcin/BAP ratio	0.79 (0.88)	0.76 (0.70)	0.77 (0.86)	0.59 (0.37)	0.76 (0.58)	0.74 (0.67)
DPD/Cr, nmol/μmol	11.6 (5.6)	12.1 (4.8)	15.3 (13.4)***	14.8 (7.2)***	13.6 (7.1)**	13.3 (8.2)***
NTx/Cr, nmol/μmol	162 (174.9)	135.4 (104.3)	214.3 (258.1)	154.7 (154.5)	127.8 (97.3)	157.2 (163.7)
25(OH)D < 50 nmol/L, n (%)	225 (82.1)	277 (87.2)	125 (73.1)*	68 (68.0)**	85 (85.9)	368 (78.0)
PTH > 6.8 pmol/L, n (%)	64 (23.3)	146 (43.3)***	92 (53.8)***	51 (51.0)***	42 (42.4)***	203 (43.0)***
DPD/Cr > 7.5 nmol/μmol, n (%)	205 (74.8)	296 (87.8)***	157 (91.8)***	94 (94.0)***	90 (90.9)**	415 (87.9)***

Notes:

* P < 0.05;

** P < 0.01;

*** P < 0.001. Data are presented as means (standard deviation) for continuous variables and as n (%) for categorical. Calcium was albumin-corrected. Statistically significant differences in variables in patients with CVD compared to those without CVD are shown in bold.

Abbreviations: CVD, cardiovascular disease; AF, atrial fibrillation; 25(OH)D, 25-hydroxyvitamin D; PTH, parathyroid hormone; BAP, bone-specific alkaline phosphatase; DPD/Cr, urinary deoxypyridinoline adjusted for creatinine; NTx/Cr, urinary cross-linked N-telopeptides of type I collagen adjusted for creatinine; CHD, coronary heart disease.

Table 3 Pearson correlation coefficients between serum PTH levels and selected clinical, mineral, and bone metabolism factors in older hip-fracture patients with and without cardiovascular disease

	With CVD		Without CVD
	r	P	r	P
Age	0.178	0.017	0.329	0.001
Sex (m)	−0.127	0.092	−0.242	0.018
HF type (cervical)	−0.148	0.05	−0.225	0.028
Dementia	−0.076	0.31	0.229	0.026
Calcium	−0.312	<0.001	−221	0.034
BAP	0.165	0.032	0.072	0.491
eGFR	−0.373	<0.001	−0.249	0.015
Troponin I	0.161	0.036	0.1937	0.056
In-hospital death	0.227	0.002	0.178	0.084

Note: Values for PTH, 25-hydroxyvitamin D, mineral and bone turnover parameters, and eGFR were log-transformed. Values in bold indicate statistically significant P values.

Abbreviations: PTH, parathyroid hormone; CVD, cardiovascular disease; BAP, bone-specific alkaline phosphatase; eGFR, estimated glomerular filtration rate; HF, hip fracture.

Table 4 Independent factors associated with the presence of cardiovascular disease in older hip-fracture patients

	OR	95% CI	P-value
PTH > 6.8 pmol/L	2.60	1.30–5.20	0.007
DPD/Cr > 7.5 nmol/μmol	2.77	1.21–6.55	0.016
Age	1.04	1.01–1.09	0.046

Notes: Adjustments for age, sex, eGFR < 60 mL/minute/1.73 m², 25(OH) D < 50 nmol/L, urinary DPD/Cr > 7.5 nmol/μmol, osteocalcin < 14 ng/mL, albumin < 33 g/L, smoking status (current and previous), alcohol consumption (≥3 times per week), dementia, type 2 diabetes mellitus and hip-fracture type. These associations remained robust after adjustment for aforementioned confounding factors and 25(OH)D < 25 nmol/L (eg, for elevated PTH: OR 2.48, 95% CI 1.25–4.92; P = 0.009).

Abbreviations: PTH, parathyroid hormone; OR, odds ratio; CI, confidence interval; DPD/Cr, urinary deoxypyridinoline adjusted for creatinine; 25(OH)D, 25-hydroxyvitamin D; eGFR, estimated glomerular filtration rate.

Table 5 Multivariate-adjusted odds ratio for the presence of cardiovascular disease in older hip-fracture patients with elevated serum parathyroid hormone levels (>6.8 pmol/L)

	OR	95% CI	P-value
Hypertension	1.97	1.08–3.60	0.028
CAD	3.43	1.60–7.32	0.001
Stroke	2.57	1.07–6.15	0.034
AF	1.91	1.03–3.45	0.048
CVD (total)	2.68	1.36–2.88	0.005

Notes: Adjustments for age, sex, eGFR < 60 mL/minute/1.73 m², 25(OH) D < 50 nmol/L, urinary DPD/Cr > 7.5 nmol/μmol, osteocalcin < 14 ng/mL, albumin < 33 g/L, smoking status (current and previous), alcohol consumption (≥3 times per week), dementia, type 2 diabetes mellitus and hip-fracture type.

Abbreviations: OR, odds ratio; CI, confidence interval; CVD, cardiovascular disease; CAD, coronary artery disease; AF, atrial fibrillation; DPD/Cr, urinary deoxypyridinoline adjusted for creatinine; 25(OH)D, 25-hydroxyvitamin D; eGFR, estimated glomerular filtration rate.

Table 6 Odds ratios for presence of cardiovascular disease according to serum PTH concentrations as urinary deoxypyridinoline excretion in older patients with hip fracture

Parameters	Model	OR	95% CI	P-value
PTH > 6.8 pmol/L and DPD/Cr ≤ 7.5 nmol/μmol	1	10.27	2.11–44.93	0.004
	2	17.32	2.79–107.37	0.002
PTH > 6.8 pmol/L and DPD/Cr > 7.5 nmol/μmol	1	7.61	2.54–22.76	<0.001
	2	9.68	3.02–31.02	<0.001
PTH ≤ 6.8 pmol/L and DPD/Cr > 7.5 nmol/μmol	1	4.26	1.55 – 11.70	0.005
	2	5.33	1.83 – 15.50	0.002
PTH > 6.8 pmol/L or DPD/Cr >7.5 nmol/μmol	1	5.37	2.00–14.43	0.001
	2	7.54	2.65–21.42	<0.001

Notes: The OR compared to the reference group (both PTH and DPD/Cr in the normal range) is shown. Model 1: adjustment for age and sex. Model 2: adjustment for age, sex, smoking status, alcohol consumption, dementia, hip-fracture type, eGFR < 60 mL/minute/1.73 m², 25(OH)D < 50 nmol/L, and albumin < 33 g/L.

Abbreviations: PTH, parathyroid hormone; DPD/Cr, deoxypyridinoline corrected by urinary creatinine; OR, odds ratio; CI, confidence interval; 25(OH)D, 25-hydroxyvitamin D; eGFR, estimated glomerular filtration rate.

Figure 1 Odds ratios for presence of cardiovascular disease in older patients with hip fracture according to serum parathyroid hormone and urinary deoxypyridinoline levels.

Notes: High levels were defined as exceeding the upper limits of normal range: >6.8 pmol/L for serum PTH and >7.5 nmol/μmol for urinary DPD/Cr. Adjustment was made for age, sex, smoking status, alcohol consumption, dementia, hip-fracture type, eGFR < 60 mL/minute/1.73 m², 25(OH)D < 50 nmol/L and albumin < 33 g/L. The odds ratios compared to the reference group (both PTH and DPD/Cr in the normal range) are shown.
Abbreviations: PTH, parathyroid hormone; DPD/Cr, deoxypyridinoline corrected by urinary creatinine; 25(OH)D, 25-hydroxyvitamin D; eGFR, estimated glomerular filtration rate.

Table 7 Use of cardiovascular medications and serum parathyroid hormone and vitamin D status

Drugs	PTH, pmol/L	P-value	25(OH)D, nmol/L	P-value
ACE inhibitors
Yes	11.1 ± 9.9		38.5 ± 17.0
No	6.7 ± 4.7	0.001	39.2 ± 18.6	0.849
ARBs
Yes	6.8 ± 3.8		35.6 ± 19.0
No	7.8 ± 6.7	0.477	39.8 ± 18.0	0.298
Beta blockers
Yes	10.1 ± 7.8		36.4 ± 17.9
No	6.5 ± 5.0	0.015	39.6 ± 15.9	0.882
Ca-channel blockers
Yes	5.1 ± 2.4		41.6 ± 17.1
No	7.8 ± 6.5	0.016	38.8 ± 18.4	0.621
Statins
Yes	7.3 ± 4.7		41.2 ± 21.8
No	7.7 ± 6.6	0.766	38.6 ± 17.5	0.540

Note: Values in bold indicate statistically significant P values.

Abbreviations: ACE, angiotensin-converting enzyme; ARBs, angiotensin IIreceptor blockers; Ca, calcium; 25(OH)D, 25-hydroxyvitamin D.

Figure 2 Diagram showing significant independent relationships (as documented by multiple regression analyses) between cardiovascular disease and parameters of mineral-bone metabolism, age and sex and short-term outcomes.

Notes: Minus signs imply a negative (inverse) relationship; myocardial injury defined as cardiac troponin I rise (>0.06 μmol/L).
Abbreviations: CVD, cardiovascular disease; SHPT, secondary hyperparathyroidism (PTH > 6.8 pmol/l); high DPD/Cr, deoxypyridinoline corrected by urinary creatinine excretion > 7.5 nmol/μmol; CKD ≥ 3, chronic kidney disease stage 3 or higher (eGFR < 60 mL/minute/1.73 m²); LOS, length of hospital stay; PTH, parathyroid hormone; eGFR, estimated glomerular filtration rate.