Discussion
VDD is a common condition that can be seen in all age groups worldwide, especially in winter, and causes several adverse outcomes, including cardiovascular diseases (38). The removal of inhibitory effects on the RAAS system and proinflammatory cytokines can be accepted as the primary mechanism for cardiovascular involvement in VDD (13,15,16,37). Hyperparathyroidism cases secondary to VDD are not uncommon and lead to adverse cardiac outcomes (20,38).
Menopause may be considered a risk factor for VDD and, consequently, secondary hyperparathyroidism (28,39). It is also known that cardiovascular risk increases in menopause with hormonal changes (29,39). Therefore regardless of the confounding factors, we aimed to reveal the differences that secondary hyperparathyroidism will create on endothelial and diastolic functions, if present, using echocardiography, carotid and brachial tDi in premenopausal women with VDD.
As stated before, the prevalence of secondary hyperparathyroidism is approximately 18-25% according to vitamin D levels, the prevalence of secondary hyperparathyroidism in severe VDD (<10 ng/ml) was shown as 33%. In Gómez-Alonso C et al. study, the autumn-winter months covered 60% of the study period in 40°N latitude in a city 400 meters above sea level (20). However, Islam MZ. et al. showed that this prevalence could vary in the range of 16% and 89%, according to ethnic differences (40). Secondary hyperparathyroidism was observed with a rate of 39.7% in our study. Ethnic differences, characteristics of the city, and the time interval may have influenced these differences.
In the secondary hyperparathyroidism group, A wave durations were longer, and E/A ratios were lower than the group with normal PTH levels(p values are 0.042 and 0.031, respectively) . It can be accepted that the prolongation of the A wave duration is effective in decreasing the E/A ratio. In Pandit A. et al. study investigating VDD and left ventricular diastolic dysfunction in a population of 67% women, there was no significant relationship between vitamin D levels and diastolic parameters (Deceleration time, e’ wave, E/A, and E/e’ ratios) (41). In Pilz S. et al. study, which evaluated approximately 600 patients over 65 years of age, the prevalence of diastolic dysfunction might increase seasonally in VDD. Even in the seasons with high risk, VDD lost its significance when adjusted for age and cardiovascular risks (42).
In ’the fifth Tromso study,’ myocardial systolic contraction rates were significantly lower in the secondary hyperparathyroidism group (approximately 100 patients), even after adjustments for covariables(for lateral s’ and septal e ’, s’ waves; p <0.05) . In the follow-up of these patients 6-12 months later, in case of persistently elevated PTH, a similar trend was observed in myocardial systolic contraction velocities, but the significance is lost. This study’s difference from our study was that the mean VitD values after the relevant unit conversions​​(nmol/l to ng/ml) were 17.2±5.0 in the high PTH group and 18.7±5.4 ng/ml in the normal PTH group(p>0.05) (In our study VitD levels 8.1±4.1 and 9.3±7.8 ng/ml; respectively) . Also, no significant difference was found in diastolic parameters (E, A waves, IVRT, pulmonary vein atrial reversal flow) in ’the fifth Tromso study.’ (43).
The study’s design differences, the population, the city where the study was conducted, and some other factors may have been influential in these differences. Suppose we interpret the findings of diastolic parameters in our study; there may be additional impairment in diastolic functions due to PTH levels in vitamin D deficiency, even if there is no confounding factor.
Lim S. et al. showed VDD is associated with endothelial dysfunction and coronary atherosclerosis (44). In diabetic nephropathy patients, VDD is significantly linked with increase in carotid IMT, but no significant relation was found in chronic renal failure patients (45,46). Studies conducted with chronic renal failure and secondary hyperparathyroidism found a significant relationship between carotid thickness and PTH levels (47). In Yankouskaya L. et al. study, which investigates women with arterial hypertension, the effects on endothelial dysfunction were explained by the pathogenic relationship between VDD and PTH levels, not a single factor (48).
Our study carotid IMT mean values are 0.6±0.1 mm in secondary hyperparathyroidism and 0.5±0.1 mm in the group with normal PTH levels(p=0.034) , no other significant difference related to carotid and brachial artery. We can say that hyperparathyroidism may cause an increase in carotid intima thickness independent of other risk factors in VDD.
As a result, we observed a significant relationship between PTH levels and endothelial (carotid IMT) and diastolic functions (A wave duration, E/A ratio) in premenopausal women with VDD, independent of all other confounding factors. Therefore, patients should be evaluated in terms of possible future cardiac risks by paying attention to PTH levels in diagnosing VDD.