Clinical Research

2017  |  Vol: 3(6)  |  Issue: 6 (November-December)
Are hypertension and the using of amlodipin increase the risk of Parkinson's disease?

Rizaldy Taslim Pinzon1*, Florentina Kassandra2, Rosa De Lima Renita Sanyasi3

1Duta Wacana Christian University School of Medicine, Dr. Wahidin Sudirohusodo 5-25, Special Region of Yogyakarta, Indonesia, 55224

2Faculty of Pharmacy Sanata Dharma University, Affandi Tromol Pos 29, Special Region of Yogyakarta, Indonesia, 55002

3Internship Doctor at dr. Efram Harsana Air Force Hospital, Raya Solo, Magetan, East Java, Indonesia, 63392

*Corresponding author:

Rizaldy Taslim Pinzon, MD, PhD,

Duta Wacana Christian University School of Medicine

Dr. Wahidin Sudirohusodo 5-25, Special Region of Yogyakarta, Indonesia, 55224


Abstract

Background: Parkinson’s disease (PD) is a neurodegenerative in central nervous system, characterized by tremor, rigidity, akynesia, and postural instability. Previous studies showed hypertension and certain drug, such as amlodipin, increasing PD risk. But the results from previous studies are conflicting. Objective: This study aimed to measure the risk of PD related to hypertension and use of amlodipin. Method: This study is a case control study. The case group were 59 PD patients and the control group were 118 patients without PD at Bethesda Hospital, matched by age and gender. Each subject on both group were agree to be interviewed and signed the informed consent form. Supplementary data obtained from medical record. The data were analyzed using chi square test and fisher test, continued by multivariate analysis using logistic regression analysis. Results: The subjects were dominated by male (50.8%) and >60 years old (87.7%). The proportion of hypertension in PD group is 35 subjects. The proportion of hypertension in control group is 84 subjects. This study showed that hypertension did not increase the risk of PD (p: 0.113). The most common prescribed antihypertensive drug was amlodipine 5 mg. Most of subjects using amlodipin alone rather than combination (66.2% vs 2.6%) and have been using amlodipin for ≥2.5 years. Bivariate analysis showed that among patients with hypertension, the use of amlodipin does not increase the risk of PD (p: 0.733). Conclusion: The results of this study showed that hypertension and the using of amlodipin do not increase the risk of PD.

Keyword: Parkinson, hypertension, amlodipin, anti hypertensive drug


Introduction

Parkinson’s Disease (PD) is a neurodegenerative disease and considered as a movement disorder (Biaggioni, 2007).  PD characterized by loss of dopaminergic neurons in the central nervous system, most notably in the basal ganglia and substantia nigra (Gallo and Garber, 2011). PD’s main symptoms are tremor, bradykinesia, rigidity and postural instability (Jankovic, 2008). The inability of cells to regulate Ca2+ is one of pathological mechanism in PD (Zaichick et al., 2017). Understanding the mechanisms by which Ca2+ signaling contributes to the progression of this disease will be crucial for the development of effective therapies and to slow PD progression (Rios et al., 2014).

PD is affecting approximately 7 to 10 million people around the world, according to the Parkinson’s Disease Foundation (Pringsheim et al., 2014). The prevalence rate of PD in European countries is estimated from 65.6 per 100 000 to 12500 per 100 000, and the incidence from 5 per 100 000 to 346 per 100 000. In Asian countries, the crude prevalence rates seem to be lower and range from 15 per 100 000 to 328 per 100 000 (Chen and Tsai, 2010).  Indonesia’s death rate caused by PD was in the 5th place in Asia or the 12th in worldwide (Noviani, 2010).

Blood pressure (BP) abnormalities have been known in PD patients (Tsukamoto et al., 2013). Previous study did not support an association between hypertension (HT) and PD and the risk of PD seems to be lower in hypertensive than in normotensive subjects (Mazza et al., 2013). Calcium channel blockers (CCB) is frequently used for treatment of HT and there was a report of drug induce parkinsonism caused by CCB (Pinzon and Adnyana, 2015). Some studies stated CCB decrease the PD risk (Biglan and Simuni, 2014). But the results from previous studies are conflicting. This study aimed to measure the risk of PD related to hypertension and use of CCB.

Materials and method

Study design

This study was a case control study matched by gender and age (±5 years). The case subjects were PD patients and the control subjects were non PD patients at Bethesda Hospital, Yogyakarta, Indonesia. The information were obtained from interview after given an informed consent. Other data were collected from subjects’ medical record.

Subjects and sampling method

The inclusion criteria of case subjects i.e.: (i) have a PD, (ii) agreed to be interviewed, and (iii) signed the informed consent form. The inclusion criteria of control subjects i.e.: (i) have not a PD, (ii) agree to be interviewed, and (iii) signed the informed consent form. The exclusion criteria of case and control subjects were incomplete data. This study was using consecutive sampling method. All subjects matched the inclusion criteria would be taken until reach the desired number.

Measurement

The interview was conducted based on previous research entitled Association of Blood Pressure and Hypertension With the Risk of Parkinson Disease: The National FINRISK Study. The data obtained from interview and medical record include: age, gender, family history of PD, HT, type 2 diabetes mellitus (DM), hypercholesterolemia, alcohol consumtion, coffee consumtion, tea consumtion, smoking, exercise, antihypertensive medication, and head trauma history.

Age differed into 2 groups: > 60 years and ≤ 60 years. Family history of PD defined as subjects who had PD on first degree relative(s), thus classified into subjects with family history of PD and subjects without family history of PD. HT defined as subjects with systolic blood pressure ≥140 mmHg diastolic blood pressure ≥90 mmHg, and/or consuming antihypertensive drug. DM defined as subjects with fasting plasma glucose ≥126 mg/dL, 2 hours plasma glucose ≥200 mg/dL during oral glucose tolerance test, random plasma glucose ≥200 mg/dL with classic symptoms of hyperglycemia, A1C ≥6.5%, consuming antidiabetic drugs, and/or using insulin. Hypercholesterolemia defined as subjects with total cholesterol level > 200 mg/dL and/or consuming lipid lowering drug.

Alcohol consumtion defined as subjects with regular consumtion of alcohol, thus differed into subjects with regular alcohol consumtion and subjects without regular alcohol consumtion. Coffee consumtion classified into 3 groups: (i) no regular coffee consumtion, (ii) 2 cups per day, and (iii) 3-4 cups per day. Tea consumtion classified into 3 groups: (i) no regular tea consumtion, (ii) 1-2 cup(s) per day, and (iii) ≥ 3 cups per day. Smoking classified into 4 groups: (i) no regular smoking, (ii) 1-9 cigarette(s) per day, (iii) 10-19 cigarettes per day, and (iv) ≥20 cigarettes per day. Exercise classified into 4 groups: (i) no regular exercise, (ii) 1-2 time(s) per week, (iii) 3-4 times er week and (iv) ≥ 5 times per week. Head trauma history defined as any repetitive trauma on head, or any trauma on head which is causing decrease/loss of consciousness and/or hospitalization.

Antihypertensive medication differed into subjects with CCB medication and subjects without CCB medications. CCB medication assesed in this study include amlodipin and nifedipin. Subjects with amlodipin medication further differed into subjects with amlodipin medication only and subjects with amlodipin combination with other antihypertensive drug(s). Duration of amlodipin medication classified into < 2.5 years and ≥ 2.5 years. There were 2 amlodipin dosage measure in this study: 5 mg and 10 mg.

Statistical analysis

All of data were analyzed by using SPSS programme. Univariate analysis was performed to identify subjects characteristics. Chi square test and fisher test as bivariate analysis was conducted to analyse factor(s) contributing to PD. A logistic regression analysis was performed to determine the independent factor(s) increasing risk of PD. Statistical significance was set at p <0.05.

Ethical clearance

This study was verified by Duta Wacana Christian University Ethical Research Committee. The number of ethical clearance was 252/C.16/FK/2016.

Results

There were total 177 subjects consist of 59 case subjects and 118 control subjects. Subjects were dominated by male (50.8%) and age > 60 years (87%). Most of subjects had not a family history of PD (91%). Only 20.9% subjects with DM and 38.4% with hypercholesterolemia (Table 1). Four percent of subjects consume alcohol, 26% consume coffee, 75.7% consume tea, 4.6% smoking, and 55.9% doing an exercise regularly. As much as 71.2% subjects had not a head trauma.

Table 1. Subjects’ Characteristics

Characteristics

n (%)

Total (%)

Parkinson

Without Parkinson

Age

-          ≤ 60 years

-          > 60 years

 

6 (10.2)

53 (89.8)

 

17 (14.4)

101 (85.6)

 

23 (13.0)

154 (87.0)

Gender

-          Male

-          Female

 

30 (50.8)

29 (49.2)

 

60 (50.8)

58 (49.2)

 

90 (50.8)

87 (49.2)

Family History of PD

-          Yes

-          No

 

10 (5.6)

49 (27.7)

 

6 (5.1)

112 (94.9)

 

16 (9.0)

161 (91.0)

DM

-          Yes

-          No

 

4 (6.8)

55 (93.2)

 

33 (28.0)

85 (72.0)

 

37 (20.9)

140 (79.1)

Hypercholesterolemia

-          Yes

-          No

 

24 (40.7)

35 (59.3)

 

44 (37.3)

74 (62.7)

 

68 (38.4)

109 (61.6)

Alcohol Consumtion

-          Yes

-          No

 

6 (10.2)

53 (89.8)

 

1 (0.9)

117 (99.1)

 

7 (4.0)

170 (96.0)

Coffee Consumtion (per day)

-          No

-          2 cups

-          3-4 cups

 

40 (67.8)

17 (28.8)

2 (3.4)

 

91 (77.1)

26 (22.0)

1 (0.9)

 

131 (74.0)

43 (24.3)

3 (1.7)

Tea Consumtion (per day)

-          No

-          1-2 cup(s)

-          ≥3 cups

 

11 (18.6)

42 (71.2)

6 (10.2)

 

32 (27.1)

73 (61.9)

13 (11)

 

43 (24.3)

115 (65.0)

19 (10.7)

Smoking (per day)

-          No

-          1-9 Cigarette(s)

-          10-19 Cigarettes

-          ≥ 20 Cigarettes 

 

55 (93.2)

2 (3.4)

2 (3.4)

0

 

114 (96.6)

2 (1.6)

1 (0.9)

1 (0.9)

 

169 (95.5)

4 (2.3)

3 (1.7)

1 (0.6)

Exercise (per week)

-          No

-          1-2 time(s)

-          3-4 times

-          ≥5 times

 

30 (50.8)

5 (8.5)

6 (10.2)

18 (30.5)

 

48 (40.7)

18 (15.2)

8 (6.8)

44 (37.3)

 

78 (44.1)

23 (13.0)

14 (7.9)

62 (35.0)

Head Trauma History

-          Yes

-          No

 

22 (37.3)

37 (62.7)

 

29 (24.6)

89 (75.4)

 

51 (28.8)

126 (71.2)

PD: Parkinson’s Disease; DM: Type 2 Diabetes Mellitus

Most of subjects had a hypertension (67.2%) and was using CCB (63.2%) as their antihypertensive drug, especially amlodipin (93.1%). More than half of subjects have been using amlodipin for ≥ 2.5 years. Table 2 showed the detail of subjects’ antihypertensive medication.

Table 2. Hypertension and Antihypertensive Drugs

Characteristics

n (%)

Total (%)

Parkinson

Without Parkinson

Hypertension

-          Yes

-          No

 

35 (59.3)

24 (40.7)

 

84 (71.2)

34 (28.8)

 

119 (67.2)

58 (32.8)

Antihypertensive Drug

-          Non CCB

-          CCB

 

11 (34.4)

21 (65.6)

 

31 (37.8)

51 (62.2)

 

42 (36.8)

72 (63.2)

Amlodipin Drug

-          Amlodipin

-          Amlodipin+Combination

 

21 (65.6)

3 (14.3)

 

51 (62.2)

2 (3.9)

 

72 (63.2)

5 (6.9)

Duration Using Amlodipin

-  < 2.5 years

-  ≥ 2.5 years

 

9 (42.9)

12 (57.1)

 

25 (49.0)

26 (51.0)

 

34 (47.2)

38 (52.8)

Amlodipin Dosage

-          5 mg

-          10 mg

 

11 (52.4)

7  (33.3)

 

34 (66.7)

15 (29.4)

 

45 (62.5)

22 (30.6)

Nifedipin Dosage

-          5 mg

-          10 mg

 

0

3 (14.3)

 

0

2 (3.9)

 

0

5 (6.9)

CCB: Calcium Channel Blocker

Bivariate analysis was performed to identify significant factor(s) increasing risk of PD. Family history of PD (p: 0.009), DM (p: 0.001), and alcohol consumtion (p: 0.006) were significant increasing the risk of PD. Bivariate analysis was continued by multivariate analysis (Table 3).

Table 3. Bivariate Analysis

Characteristics

p

OR (95% CI)

Age ≤ 60 years

0.429

-

Male

1.000

-

Family History of PD

0.009

3.810 (1.311-11.066)

DM

0.001

0.187 (0.063-0.558)

Hypercholesterolemia

0.662

-

Alcohol Consumtion

0.006*

13.245 (1.556-112.773)

Coffee Consumtion: 2 cups per day

0.196

-

Tea Consumtion: 1-2 cup(s) per day

0.424

-

Smoking: 1-9 cigarette(s) per day

0.479

-

Exercise: 1-2 times per week

0.333

-

Head Trauma

Hypertension

0.078

0.113

-

-

Antihypertension drug: amlodipin

0.733

-

Antihypertension drug: amlodipin + combination

0.172*

-

Duration of using CCB: < 2.5 years

0.634

-

Amlodipin dosage: 10 mg

0.523

-

PD: Parkinson’s Disease; DM: Type 2 Diabetes Mellitus; CCB: Calcium Channel Blocker,  *Fisher Test

Multivariate analysis was made based on the result of bivariate analysis. Multivariate analysis showed alcohol consumtion and family history of PD were significant increasing risk of PD (Table 4). Alcohol consumtion increasing risk of PD by 15.744 times, whereas family history of PD increasing risk of PD by 3.450 times.

Table 4. Multivariate Analysis

Characteristics

p

OR (95% CI)

Family History of PD

0.031

3.450 (1.118-10.644)

DM

0.006

0.194 (0.060-0.623)

Alcohol Consumtion

0.019

15.744 (1.579-157.004)

PD: Parkinson’s Disease; DM: Type 2 Diabetes Mellitus

Discussion                             

Most of subjects in this study had a hypertension (67.2%). This results is parallel to previous study. PD is characterized by peculiar blood pressure (BP) abnormalities. Vetrano et al. (2017) stated the prevalence of hypertension was 60% according to office and 69% according to ambulatory BP measurements (p <0.001). In the PRIAMO (Parkinson Disease Non-Motor Symptoms) study conducted in Italy, HT was the most frequently reported concomitant, non-neurological disorder (Barone et al., 2009).

        Further analysis in this study showed HT did not increasing PD risk (p: 0.113). Simon et al. conclude the same statement. There was no association between HT and PD (Simon et al, 2007). PD risk was not significantly related to history of HT (RR: 0.96; 95% CI: 0.80-1.15) (Zhang and Tian, 2011). Research on 59 540 subjects showed there was no significant association between blood pressure and PD risk in men (Qiu et al., 2011).

Most previous studies found CCB have a protective effect to PD or decreasing PD risk. The long term use of CCB has shown a significant reduction in risk of PD (Mullapudi et al., 2016). The pooled estimate of 7 studies on the association between use of CCBs and PD showed a significant reduction in the risk of PD in the users of CCBs (RR 0.82, 95% CI 0.71–0.93) (Mullapudi et al. [2], 2016). Lee et al. (2014) suggest there is a benefit by using dihydrophyridine CCB to PD.

Dopaminergic neuron in substansia nigra have L-type Ca2+ channels in the surface. Dysregulation of L-type Ca2+ channels known as one of pathology process in PD. Continuous Ca2+ influx via L-type Ca2+ channels into the dopaminergic neurons of substantia nigra may facilitate a downstream cascade of events leading to the cell death and the progressive degeneration of PD (Belardetti and Zamponi, 2012). The Ca2+ intracellular level > 10.4 mol/L may blocked dopamine release, which is disturbance on dopamine release and/or production causing PD (Satyanegara, 2010). Target effect of dihydrophiridine CCB is on L-type Ca2+ channels. Amlodipin is one of dihydrophiridine CCB that pass the blood brain barier. By these mechanism, the using of CCB, especially dihydrophiridine CCB, reduce the PD risk and PD progression. The mechanism of lowering risk of PD was though by potential neuroprotective effect of CCB, not by lowering BP (Ritz et al., 2010; Gudala et al., 2015).

Another studies showed an different results, as stated by Ascherio and Schwarzchild (2016) the use of dihydropyridine CCB was associated with reduced PD risk in some but not all studies (. Current study conclude the using of CCB (p: 0.733) and CCB combination (p: 0.172) did not increasing or decreasing PD risk. The duration of CCB medication was not correlate to PD risk (p: 0.634). The using of amlodipin, did not significant influencing PD risk (p: 0.523). These results are similar to previous study. Ton et al. (2007) stated there was no correlation between CCB medication and PD risk. Amlodipine prescription drug use was not associated with risk of PD (Ritz et al., 2010)

Current study showed family history of PD and alcohol consumtion were increasing the risk of PD. Family history of PD increasing risk of PD by 3.450 times (95% CI: 1.118-10.644, p: 0.031). This result is parallel to some previous studies stated a family history of PD related to a higher risk of PD. Genetic studies of the glucocerebrosidase, parkin, and LRRK2 genes have contributed to our understanding of familial PD (Chen and Tsai, 2010). Wells (2009) mentioned family history of PD significantly increasing risk of PD 8.8 times on age < 70 year and 2.8 times on age > 70 year (Wells et al., 2009). Compared with never smokers with no family history of PD, never smokers who did have a family history had an OR of 2.81 (95% CI: 1.91-4.13) and for smokers with a family history, the OR was 1.60 (95% CI: 1.15-2.23) (Kenborg et al., 2015).

        This study found alcohol consumtion was increasing risk of PD by 15.744 times (95% CI: 1.579-157.004, p: 0.019). This result is consistent to previous studies. Sipetic et al. (2012) stated alcohol consumtion increasing PD risk significantly (OR: 4.78, 95% CI:2.67-8.55). Inversely, research on 214 cases within 6 years of PD onset and 327 controls without neurodegenerative disease did not find any significant interactions between alcohol drinking (Fukushima et al., 2010). There are some possibilities causing the different result i.e.: this study did not measure the amount of alcohol daily intake percisely. Subjects’ bias also considered as an important factor of this differences.

This study found age ≤ 60 years was not significant increasing PD risk (p: 0.429). This results is reasonable because increasing age has been found to be the most consistent risk factor for the development of PD (Tan, 2013). A research in Italian population by Pupillo et al. (2016) reported older age, but not younger age, was associated with increased PD risk. Young onset Parkinson's disease (<50 years) is more likely to be genetic than older onset Parkinson's disease, particularly with a positive family history, and there are also racial differences (Malek et al., 2013). In old age, the dopaminergic neurons seem increasingly rely on L-type calcium channels for their activation and so were more vulnerable to neurologic damage (Chan et al., 2007). Bivariate analysis on gender showed the p value was 1.000. Thus, there is no association between gender and PD risk. This statement is same to study by Taylor et al. (2007) reported no gender differences on PD prevalence.

DM was found to be a protective factor to PD in this study (OR: 0.194, 95% CI: 0.060-0.623, p: 0.006). Study by Driver et al. (2008) did not suggest that diabetes is a preceding risk factor for PD. Previous case control studies stated the association between DM and PD risk was not significant (OR: 0.75, 95% CI: 0.50–1.11; p: 0.835) (Cereda et al., 2011). Lu et al. (2014) reported a decrease of PD risk among DM subjects (OR: 0.75, 95% CI: 0.58–0.98).

Other study showed a different result. PD among subjects with DM, compared with those without it, were 1.80 (95% CI 1.03–3.15) in men, 1.93 (1.05–3.53) in women, and 1.85 (1.23–2.80) in men and women combined (adjusted also for sex) (Hu et al., 2007). Current study did not make a differentiation between DM after PD onset or DM before PD onset and may lead to different result.

Hypercholesterolemia was not significant increasing risk of PD in the present study (p: 0.662). Previous case control study including 124 PD cases and 112 controls had the same result, serum total cholesterol did not differ significantly between PD patients and controls (Huang et al., 2007). A large retrospective case-control study did not find any association between serum total cholesterol and the occurrence of idiopathic PD (Hu, 2010).

On the contrary, the secondary analysis of the DATATOP trial provides preliminary evidence that higher total serum cholesterol concentrations may be associated with a modest slower clinical progression of PD (Huang et al., 2011). Present study only asked the subjects about their history of hypercholesterolemia and/or look at their medical record, but did not measure the actual total cholesterol level when the study conducted. This study also did not differentiate between hypercholesterolemia before or after PD onset. It may be the caused of the difference of the result.

        Current study stated coffee consumtion (p: 0.196) and tea consumtion (p: 0.424) were not significant increasing or decreasing PD risk. These results is contrary to many previous studies. Coffee and tea consumtion found to be a protective factors of PD. Tanaka et al. (2011) stated the intake of coffee and caffeine reduced the risk of PD. Coffee and black tea, but not green tea, seemed to be protective to PD (Gaba, 2015). A meta-analysis by Li et al. (2012) showed tea drinking can lower the risk of PD, the pooled OR (95% CI) was 0.85 (0.74–0.98), which suggests the protective effect of tea drinking in PD risks. The differences between current study to previous study differences may be caused by several reasons. This study did not differentiate the type of coffee (decaffeinated coffee and caffeinated coffee) and tea (black tea and green tea).

        Animal studies indicate that caffeine is neuroprotective. The administration of caffeine to maneb- and paraquat-treated rodents reduced the number of degenerating dopaminergic neurons (Kachroo et al., 2010; Yadav et al., 2012). Genetic and pharmacological data from rodent studies indicate that caffeine reduces dopaminergic toxicity and slows disease progression (Xiao et al., 2011; Sonsalla et al., 2012). Polyphenols in green and black tea extracts provide a highly potent antioxidant-radical activities in brain mitochondrial membrane fractions (Zhao, 2009). Polyphenols in tea reduce occurrence of disease and provide neuroprotection in cell culture and animal models (Seidl et al., 2014).

        Smoking was not increasing or decreasing risk of PD significantly (p: 0.479). Many previous studies conclude smoking as a protective factor or decreasing risk of PD. Ritz et al. (2007) stated a dose-dependent reduction of PD risk associated with cigarette smoking. A matched case-control study on 92 individuals with PD and  184 people without PD found that individuals with PD are significantly less likely to have smoked regularly than those without PD (Masoud, 2008). Stratified analyses indicated that smoking duration was associated with lower PD risk within fixed intensities of smoking. Compared with never smokers, the ORs among past smokers who smoked > 20 cigarettes/day were 0.96 for 1 - 9 years of smoking, 0.78 for 10-19 years, 0.64 for 20-29 years, and 0.59 for 30 years or more (p for trend: 0.001) (Chen et al., 2011). The possibilities reasons of these differences i.e.: current study did not measure the duration of smoking.

        Nicotine has long been considered as a possible therapeutic agent for PD (Quik et al., 2008). Cigarette smoke has been shown to inhibit monoamine oxidase (MAO) activity, which is MAO is known to breakdown dopamine. Several studies also suggest that nicotine stimulates dopamine release (Miller and Das, 2007).

        Exercise was not correlate to PD risk (p: 0.333). Past study showed an inverse result. The risk of developing PD appeared to be inversely associated with the amount of exercise practiced throughout life (OR: 0.65, 95% CI: 0.51–0.83, p <0.0001). People who practice physical exercise during these two periods of their life have a 40% lower risk of PD than people who remained inactive during the same periods (Xu et al., 2010). PD risk in late adult life was strongly inversely associated with physical exercise during high school and college or at age 35-39 years (Ascherio and Schwarzchild, 2016). Research by Yang, et al. (2015) found that a medium level of daily total physical activity is associated with a lower risk of PD, especially in males. Current study did not measure the duration of exercise and years of physically active. It may be the reason of the different results.

        Exercise could potentially influence endogenous production and release of dopamine in patients with PD, leading to enhanced dopaminergic neurotransmission. Exercise could also postpone the onset of parkinsonism (Speelman et al., 2011). Exercise limits the alteration in dopaminergic neurons in the substantia nigra and contributes to optimal functioning of the basal ganglia involved in motor commands and control by adaptive mechanisms involving dopamine and glutamate neurotransmission. In response to exercise, the concentration of dopamine increases and the receptors of this neurotransmitter enhance their sensitivity (Paillard et al., 2015).

        History of head trauma did not correlate to PD risk in present study (p: 0.078). This result is parallel to research by Kenborg et al. (2015) stated examination of number of head injuries or hospitalization for a head injury did not show an association with PD. For 954 study subjects with at least one head injury, there was no evidence of an association between loss of consciousness, duration of loss of consciousness, or amnesia and risk for PD. Another studies by Lee et al. (2012) and Jafari et al. (2013) suggested a different results. In logistic regression analyses, we observed a 2-fold increase in risk of PD for subjects who reported a traumatic brain injury (Lee et al., 2012). The pooled OR for the association of PD and head trauma was 1.57 (95% CI: 1.35-1.83) (Jafari et al., 2013).

Conclusion

Hypertension and amlodipin do not increase the risk of PD. Family history of PD and alcohol consumtion are increasing risk of PD, whereas DM is a protective factor of PD.

Conflicts of Interests

All authors have none to declare.

References

Ascherio A, Schwarzchild MA. 2016. The epidemiology of parkinson’s disease and prevention. Lancet Neurology 15:1257-72.

Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, Bottacchi E, Cannas A, Ceravolo G, Ceravolo R, Cicarelli G, Gaglio RM, Giglia RM, Iemolo F, Manfredi M, Meco G, Nicoletti A, Pederzoli M, Petrone A, Pisani A, Pontieri FE, Quatrale R, Ramat S, Scala R, Volpe G, Zappulla S, Bentivoglio AR, Stocchi F, Trianni G, Dotto PD; PRIAMO study group. 2009. The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Movement Disorder 24:1641–9

Belardetti F, Zamponi GW. 2012. Calcium channels as therapeutic targets. WIREs Membrane Transport and Signaling 1: 433-51.

Biaggioni I. 2007. Parkinson’s disease, autonomic neuronopathy with impaired cardiovascular regulatation. Hypertension 49: 21-2.

Biglan KM, Simuni T. 2014. Harnessing existing drug to slow progression of parkinson’s disease: the STEADY-PDIII Trial os isradipine. Practical Neurology 28-31.

Cereda E, Barichella M, Pedrolli C, Klersy C, Cassani E, Caccialanza R, Pezzoli G. 2011. Diabetes and risk of parkinson’s disease. Diabetes Care 34: 2614-23.

Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ. 2007. Rejuvenation protects neurons in mouse models of Parkinson’s disease. Nature 447:1081–108.

Chen H, Huang X, Guo X, Mailman RB, Park Y, Kamel F, Umbach DM, Xu Q, Hollenbeck A, Schatzkin A, Blair A. 2011. Smoking duration, intensity, nad risk of parkinson disease. Neuorology 74: 878-84.

Chen SY, Tsai ST. 2010. The epidemiology of parkinson’s disease. Tzu Chi Medical Journal 22(2):74-81.

Driver JA, Smith A, Buring JE, Gaziano JM, Kurth T, Logroscino G. 2008. Prospective cohort study of type 2 diabetes and the risk of parkinson’s disease. Diabetes Care 31: 2003-5.

Fukushima W, Miyake Y, Tanaka K, Sasaki S, Kiyohara C, Tsuboi Y, Yamada T, Oeda T, Miki T, Kawamura N, Sakae N, Fukuyama H, Hirota Y, Nagai M. 2010. Alcohol drinking and risk of parkinson’s disease: a case-control study in Japan. BMC Neurology 10:111.

Gaba A. 2015. Recent studies on nutrition and parkinson’s disease prevention: a systematic review. Open Journal of Preventive Medicine 5:197-205

Gallo PM, Garber CE. 2011. A comprehensive approach to exercise prescription for the health fitness profesional. ACSM’s Health & Fitness Journal 15(4): 8-17.

Gudala K, Kanukula R, Bansal D. 2015. Reduced risk of parkinson’s disease in users of calcium channel blockers: a meta-analsis. International Journal of Chronic Disease doi: 10.1155/2015/697404.

Huang X, Auinger P, Eberly S, Oakes D, Schwarzschild M, Ascherio A, Mailman R, Chen H. 2011. Serum cholesterol and the progression of parkinson’s disease: results from DATATOP. PloS ONE 6(8): e22854.

Huang X, Chen H, Miller WC, et al. 2007. Lower low-density lipoprotein cholesterol levels are associated with Parkinson’s disease. Movement Disorders 22(3): 377–81.

Hu G. 2010. Total cholesterol and the risk of parkinson’s disease: a review for some new finding. Parkinson’s Disease doi:10.4061/2010/836962.

Hu G, Jousilahti P, Bidel S, Antikainen R, Tuomilehto J. 2007. Type 2 diabetes and the risk of parkinson’s disease. Diabetes care 30: 842-7.

Jankovic J. 2008. Parkinson’s disease: Clinical features and diagnosis. Journal Neurology Neurosurgery Psychiatry 79: 368376.

Jafari S, Etminam M, Aminzadeh F, Samii A. 2013. Head injury and risk of parkinson disease: a systematic review and meta-analysis. Movement Disorder 28(8):1222-9.

Kachroo A, Irizarry MC, Schwarzschild MA.2010. Caffeine protects against combined paraquat and maneb-induced dopaminergic neuron degeneration. Experimental Neurology 223: 657–61.

Kenborg L, Lassen CF, Ritz B, Andersen KK, Christensen J, Schernhammer ES, Hansen J, Wermuth L, Rod NH, Olsen JH. 2015. Lifestyle, family history, and risk of idiopathic parkinson disease: a large Danish case-control study. American Journal of Epidemiology 181(10): 808-16.

Kenborg L, Rugbjerg K, Lee PC, Ravnskjær L, Christensen J, Ritz B, Lassen CF. 2015. Head injury and risk for parkinson disease. Neurology 84(11): 1098-103.

Lee PC, Bordelon Y, Bronstein J, Ritz B. 2012. Traumatic brain injury, paraquat exposure, and their relationship to parkinson disease. Neurology 79: 2061-6.

Lee YC, Lin CH, Wu RM, Lin JW, Chang CH, Lai MS. 2014. Antihypertensive agents and risk of parkinson’s disease: a nationwide cohort study. PloS ONE 9(6): e98961.

Li FJ, Ji HF, Shen L. 2012. Meta-analysis of tea drinking and risk of parkinson’s disease. The Science World Journal doi:10.1100/2012/923464.

Lu L, Fu DL, Li HQ, Liu AJ, Li JH, Zheng GQ. 2014. Diabetes and risk of parkinson’s disease: an updated meta-analysis of case control studies. PloS ONE 9(1): e85781.

Masoud SA. 2008. Does cigarette smoking have a protective effect againts parkinson’s disease. International Journal of Pharma and Bio Science 2(2): 46-49.

Mazza A, Ravenni R, Antonini A, Casiglia E, Rubello D, Pauletto P. 2013. Arterial hypertension, a tricky side of parkinson’s disease: physiopathology and therapeutic features. Neurology Science 34: 621-7.

Miller LR, Das SK. Cigarette Smoking and Parkinson’s disease. Excli Journal 2007;6:93-99.

Mullapudi A, Gudala K, Boya C, Bansal D. 2016. Use of anihypertensive agents and risk of parkinson’s disease: a meta-analysis of observational studies. Value in Health 19:A100.

Mullapudi A, Gudala K, BoyaCS, Bansal D. 2016. Risk of parkinson’s disease in the users of antihypertensive agents: an evidence from the meta-analysis of observasional studies. Journal of Neurodegenerative Disease doi.org/10.1155/2016/5780809.

Noviani E. 2010. Hubungan Antara Merokok Dengan Penyakit Parkinson di RSUD Prof. DR. Margono Soekarjo Purwokerto. Mandala of Health 4(2): 81-6.

Malek N, Bajaj N, Barker R, et al. 2013. Family history in young onset parkinson’s disease. Journal of Neurology, Neurosurgery & Psychiatry doi:10.1136/jnnp-2013-306573.160.

Paillard T, Rolland Y, Barreto PS. 2015. Protective effects of physical exercise in alzheimer’s disease and parkinson’s disease: a narrative review. Journal Clinical Neurology 11(3):212-9.

Pinzon R, Adnyana K. 2015. “Penyakit Parkinson”. pp.1-24, Yogyakarta: Betha Grafika.

Pringsheim T, Jette N, Frolkis A, Steeves TD. 2014. The prevalence of Parkinson’s disease: A systematic review and meta-analysis. Movement Disorder 29:1583-90.

Pupillo E, Cricelli C, Mazzoleni F, Cricelli I, Pasqua A, Pecchioli S, Lapi F, Beghi E. 2016. Epidemiology of parkinson’s disease: a population-based study in primary care in Itali. Neuroepidemiology 47:38-45.

Qiu C, Hu G, Kivipelto M, Laatikainen T, Antikainen R, Fratiglioni L, Jousilahti P, Tuomilehto J. 2011. Association of blood pressure and hypertension with the risk of parkinson disease, the national FINRISK study. Hypertension 57:1094-100.

Quik M, O’Leary K, Tanner CM. 2008. Nicotine and Parkinson’s disease: implications for therapy. Movement Disorder 23: 1641–52.

Rios PR, Suaga PG, Fdez E, Hilfiker S. 2014.Upstream deregulation of calcium signaling in parkinson’s disease. Frontiers in Molecular Neuroscience doi: 10.3389/fnmol.2014.00053.

Ritz B, Ascherio A, Checkoway H, Marder KS, Nelson LM, Rocca WA, Ross GW, Strickland D, Van Den Eeden SK, Gorell J. 2007. Pooled analysis of tobacco use and risk of parkinson disease. Archives of  Neurology 64(7):990-7.

Ritz B, Rhodes SL, Qian L, Schernhammer E, Olsen JH, Friis S. 2010. L-type calcium channel blockers and Parkinson disease in Denmark. Annals of Neurology 67:600–6.

Satyanegara. 2010. “Ilmu Bedah Saraf”. Jakarta: PT Gramedia Pustaka Utama.

Seidl SE, Santiago JA, Bilyk H, Potashkin JA. 2014. The emerging role of nutrition in parkinson’s disease. Frontiers in Aging and Neurosciene 6(36):1-14.

Simon KC, Chen H, Schwarzschild M, Ascherio A. 2007. Hypertension, hypercholesterolemia, diabetes, and risk of Parkinson disease. Neurology 69:1688–95.

Sipetic SB, Vlajinac HD, Maksimovic JM, Marinkovic JM, Dzoljic ED, Ratkov IS, Kostic VS. 2012. Cigarette smoking, Coffee intake and alcohol consumption preceding Parkinson’s disease : a case-control study. Acta Neuropsychiatry 24(2): 109–114.

Sonsalla PK, Wong LY, Harris SL, Richardson JR, Khobahy I, Li W, Gadad BS, German DC. 2012. Delayed caffeine treatment prevents nigral dopamine neuron loss in a progressive rat model of Parkinson’s disease. Experimental Neurology 234:482–7.

Speelman AD, van de Warrenburg BP, van Nimwegen M, Petzinger GM, Munneke M, Bloem BR. 2011. How might physical activity benefit patients with parkinson disease? Nature Review Neurology 7:528-34.

Tanaka K, Miyake Y, Fukushima W, Sasaki S, Kiyohara C, Tsuboi Y, Yamada T, Oeda T, Miki T, Kawamura N, Sakae N, Fukuyama H, Hirota Y, Nagai M. 2011. Intake of Japanese and Chinese teas reduces risk of parkinson’s disease. Parkinsonism and related disorder 17:446-50.

Tan LCS. 2013. Epidemiology of Parkinson’s disease. Neurology Asia 18(3):231-8.

Taylor KS, Cook JA, Counsell CE. 2007. Heterogeneity in male to female risk for Parkinson’s disease. Journal  Neurolology Neurosurgery Psychiatry 78(8): 905-6.

Ton TG, Heckbert SR, Longstreth WT Jr, Rossing MA, Kukull WA, Franklin GM, Swanson PD, Smith-Weller T, Checkoway H. 2007. Calcium channel blockers and β-blockers in relation to parkinson’s disease. Parkinsonism Related Disorder 13(3):165-9.

Tsukamoto T, Kitano Y, Kuno S. 2013. Blood pressure fluctuation and hypertension in patients with parkinson’s disease. Brain and Behaviour 3(6): 710-4

Vetrano DL, Pisciotta MS, Brandi V, Lo Monaco MR, Laudisio A, Onder G, Fusco D, L'Angiocola PD, Bentivoglio AR, Bernabei R, Zuccalà G. 2017. Impact of disease duration and cardiovascular dysautonomia on hypertension in Parkinson’s disease. Journal Clinical Hypertension 19:418-23.

Wells BG, Dipiro JT, Schwinghammer TL, Dipiro CV. 2009. Pharmacotherpy handbook, 7th edition. Pp.360. United States: Mc Graw Hill.

Xiao D, Cassin JJ, HealyB, Burdett TC, Chen J, Fredholm BB, Schwarzschild MA. 2011. Deletion of adenosine A(1) or A((2)A) receptors reduces L-3,4dihydroxyphenylalanine-induced dyskinesia in a model of Parkinson’s disease. Brain Resesearch 1367:310–8.

Xu Q, Park Y, Huang X, Hollenbeck A,  Blair A,  Schatzkin A,   Chen H. 2010. Physical activities and future risk of parkinson disease. Neurology 75:341-8.

Yadav S, Gupta SP, Srivastava G, Srivastava PK, Singh MP. 2012. Role of secondary mediators in caffeine-mediated neuroprotection in maneb- and paraquat-induced Parkinson’s disease phenotype in the mouse. Neurochemistry Research. 37:875–884.

Yang F, Trolle Lagerros Y, Bellocco R, Adami HO, Fang F, Pedersen NL, Wirdefeldt K. 2015. Physical activity and risk of parkinson’s disease in the Swedish National March Cohort. Brain 38:269-75.

Zaichick SV, McGrath KM, Caraveo G. 2017. The role of Ca2+ signaling in parkinson’s disease. Disease Model & Mechanism 10:519-35.

Zhang P, Tian B. 2011. Metabolic syndome: an important risk factor for parkinson’s disease. Oxidative Medicine and Cell Longevity doi.org/10.1155/2014/729194.

Zhao B. 2009. Natural antioxidants protect neurons in Alzheimer’s disease and Parkinson’s disease. Neurochemical Research. 34: 630–8.

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