Effect of lipid-lowering and anti-hypertensive drugs on plasma homocysteine levels

Figures & data

Table 1 Overview of meta-analyses on homocysteine and CVD since 1995

Year and author	No. of studies Included	No of retrospective/prospective studies	Main results (OR and 95% CI)
1995 Boushey	27	24/3	Hcy + 5 μmol/L:
			1.6 (1.4–1.7) Men, CAD
			1.8 (1.3–1.9) Women, CAD
			1.5 (1.3–1.9) Cerebrovasc.
2000 Moller	12	8/4	Hcy > 95th percentile:
			3.97 (3.07–5.12) Cerebrovasc.
2000 Cleophas	33	22/11	elevated Hcy (no further def.)
			1.49 (1.33–1.67) prospective CAD
			1.62 (1.50–1.74) retrospect. CAD
2002 Kelly	14	11/3	HHcy (binary variable)
			1.79 (1.61–2.0) Stroke
2002 Wald	20	−/16	IHD, 8 Stroke Hcy + 5μmol/L:
			1.32 (1.19–1.45) IHD
			1.59 (1.29–1.96) Stroke
2002 Ford	38 CHD	26/12	Hcy + 5 μmol/L
			1.23 (1.07–1.41) prospective
			1.70 (1.50–1.93) retrospective
	24 stroke	17/7	1.58 (1.35–1.85) prospective
			2.16 (1.65–2.82) retrospective
2002 Hcy Studies Collaboration	30	IHD: 15/12	Hcy — 25%
			0.83 (0.77–0.89) prospective IHD
			0.67 (0.62–0.71) retrospect. IHD
		Stroke: 5/8	0.77 (0.66–0.90) prospective stroke
			0.86 (0.73–1.01) retrospect. stroke

Abbreviations: CAD, coronary artery disease; CHD, coronary heart disease; CI, confidence interval; OR, odds ratio; IHD, ischemic heart disease; Hcy, homocysteine; HHcy, hyperhomocysteinemia.

Table 2 Effect of fibrates on homocysteine concentration (mean ± standard deviation, unless otherwise noted)

Study	N	treatment Fenofibrate	tHcy before	tHcy after	% change	P
de Lorgeril 1999	29	200 mg/d,12 weeks	11.4 ± 3.5	16.6 ± 5.2	+ 56 %	<0.001
Dierkes 1999	10	200 mg/d, 6 weeks	13.1	20.0	+ 44 (.8 ± 85) %b	a<0.001
Landray 1999	8	according to renal failure, 8 weeks	15.1	21.8	+ 44 %	ap = 0.03
Giral 2001	29	200 mg/d, 6 months	12.3 ± 3.9	16.2 ± 4.6	+ 32 %	<0.001
Bissonnette 2001	20	200 mg/d, 8 weeks	10.3 ± 3.3	14.1 ± 3.8	+ 37 %	<0.001
Dierkes 2001	25	200 mg/d, 6 weeks	10.7	14.0	44 ± 47 %b	a<0.001
Westphal 2001	22	200 mg/d, 6 weeks	10.7	14.4	+ 35 %	a<0.001
Stulc 2001	11	200 mg/d, 9 weeks	12.3 ± 3.2	19.1 ± 7.2	+ 55 %	<0.001
Melenovsky 2002	15	200 mg/d, 10 weeks	12.4 ± 2.7	16.9 ± 3.7	+ 36 %	<0.001
Melenovsky 2003	19	200 mg/d, 65 ± 18 days	11.5 ± 3.0	17.5 ± 6.5	+ 52 %	not provided
Mayer 2003	24	200 mg/d, 3 months	10.0 ± 2.9	14.2 ± 2.9	+ 42 %	not provided
Milionis 2003	22	200 mg/d, 12 weeks	10.3 ± 3.3	14.2 ± 3.6	+ 38 %	<0.001
Genest 2004	418	200 mg/d, 3 years	11.0 ± 5.6	16.5 ± 10.7	+ 55 %	<0.001
DAIS-Study
		Bezafibrate
Dierkes 1999	10	400 mg/d, 6 weeks	11.9	15.5	+17 (.14 .65) %b	ap = 0.02
Jonkers 1999	16	400 mg/d, 6 weeks	11.9 ± 2.1	14.1 ± 2.9	+ 18 %	<0.001
Harats 2001	12	400 mg/d, 6 weeks	8.2 ± 2.3	6.8 ± 1.4	−17 %	p = 0.22
		Ciprofibrate
Harats 2001	26	100 mg/d, 12 weeks	6.8 ± 1.8	10.6 ± 4.3	+ 56 %	<0.0001
		Gemfibrozil
Westphal 2001	22	900 mg/d, 6 weeks	12.9	12.4	−4 %	aNS
Syvänne 2004
LOCAT-Study	395	900 mg/d, 16 months	12.6	14.1	+ 11.9%	a<0.0001

a Notes: Median;

b calculated from individual data.

Abbreviations: ACE inhibitor, angiotensin-converting enzyme inhibitor; BIP, bezafibrate Infarction Prevention; CAD, coronary artery disease; CI, confidence interval; CVD, cardiovascular disease; DAIS, Diabetes Atherosclerosis Intervention Study; FIELD, Fenofibrate Intervention and Event Lowering in Diabetes; GFR, glomerular filtration rate; FA, folic acid; HCT, hydrochlorothiazide; LOCAT, Lopid Coronary Angiography Trial; MTHFR, methylenetetrahydrofolate reductase; PPARα, peroxisome-proliferation activated receptor alpha; PUFA, polyunsaturated fatty acids; RR, relative risk; homocysteine, total homocysteine.

Table 3 Lipid-lowering and anti-hypertensive drugs that elevate homocysteine

Drug	Effect on homocysteine	Suggested mechanisms	Evidence from
Fibric acid derivatives	increase of homocysteine:	reduction of glomerular function	Human studies, cross-sectional and clinical trials mechanistic studies in rodents
	+ 40% fenofibrate	increased creatin/creatinine
	+20% bezafibrate	metabolism
	+ 20% gemfibrozil	PPARα-activation
Niacin	increase of fasting
	homocysteine, amount unclear	effect on vitamin B6 metabolism increased methylation demand	Human studies, mechanistic studies in rodents
Diuretics	increase of fasting homocysteine +20% hydrochlorothiazide	decreased glomerular filtration rate	Human studies, cross-sectional and one clinical trial

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