Metabolic syndrome in hypertensive patients: An unholy alliance

Table 1 Prospective studies exploring the association of metabolic syndrome with cardiovascular events and all-cause mortality in hypertensive subjects

Ref.	No. of subjects (population)	Mean follow-up (yr)	Mean age (yr)	MetS (%)	MetS definition	T2DM (%)	Risk of all-cause mortality	Risk of CV events
Schillaci et al[25]	1742 (Italian hypertensives without CVD at baseline)	4.1	50	34.0	Modified ATP III	6.0	Not reported	HR = 1.73 (1.25-2.38) Cardiac events: HR = 1.48, (1.01-2.27). Cerebrovascular events: HR = 2.11 (1.27-3.50) After exclusion of T2DM HR = 1.43 (1.02-2.08)
Pierdomenico et al[27]	802 (Italian hypertensives without T2DM, TOD and CVD at baseline)	6.9	53	27.2	Modified ATP III	0	Not assessed	HR = 2.64 (1.52-4.58)
Andreadis et al[29]	1007 (Greek hypertensives without CVD at baseline)	2.1	59	42.1	Modified ATP III	13.2	Not assessed	HR = 1.75 (1.15-2.66) Cardiac events: HR = 1.73 (1.00-3.00). Cerebrovascular events: HR = 1.91 (1.01-3.58) After exclusion of T2DM: HR = 1.67 (1.01-2.74)
Zanchetti et al[28]	2034 (European hypertensives participating in the ELSA study)	3.7	56	33.3	Modified ATP III	4.5	Not assessed	Incidence of CV events not different (about 6% in subjects with and in those without MetS)
Pannier et al[22]	26447 French hypertensives without CVD at baseline	4.1	50	17.8	ATP III	Not reported	HR = 1.40 (1.13-1.74)	Not assessed
de Simone et al[30]	8243 hypertensives with EKG-LVH participating in the LIFE study	4.8	67	19.3	Modified ATP III	12.5	Not assessed	HR = 1.47 (1.27-1.71) CV death: HR = 1.73 (1.38-2.17)
Vlek et al[31]	1815 hypertensives with CVD at baseline and without T2DM	3.9	61	42.7	ATP III	0	Not assessed	HR = 1.24 (0.95-1.62) CV death: HR = 1.41 (1.01-1.98)
Gupta et al[32]	19257 hypertensives participating in the ASCOT-BPLA study	5.5	63	43.8	ATP III	27.0	HR = 1.35 (1.16-1.58)1	Stroke: HR = 1.34 (1.07-1.68)1 MI: HR = 1.16 (0.95-1.43)1

¹HR are adjusted for the individual components of MetS. MetS: Metabolic syndrome; CVD: Cardiovascular disease; ATP III: Third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults; T2DM: Type 2 diabetes mellitus; TOD: Target organ damage; CV: Cardiovascular; MI: Myocardial infarction; EKG-LVH: Left ventricular hypertrophy detected by electrocardiography; ELSA: European Lacidipine Study on Atherosclerosis; LIFE: Losartan Intervention For Endpoint reduction; ASCOT-BPLA: Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm.

Table 2 Cross-sectional studies investigating the association of metabolic syndrome with various markers of subclinical organ damage

Ref.	No. of subjects	LVM	LV diastolic	Carotid IMT	Micro-	CKD	Arterial
	(population)		function	and plaques	albuminuria		stiffness
Mancia et al[21]	2051 (Italian GP)	↑	-	-	-	-	-
Cuspidi et al[23]	447 (Italian hypertensives)	↑	-	↑	↑	-	-
Leoncini et al[24]	354 (Italian hypertensives)	↑	-	↑	↑	-	-
Mulè et al[26]	353 (Italian hypertensives)	↑	Impaired	-	↑	-	-
Mulè et al[91]	475 (Italian hypertensives)	↑	Impaired	-	-	-	-
Schillaci et al[92]	618 (Italian hypertensives)	↑1	Impaired1	-	-	-	-
Nicolini et al[93]	200 (Italian hypertensives)	↑1	Impaired1	-	-	-	-
Aijaz et al[94]	2042 (United States GP)	↑1	Impaired1	-	-	-	-
Sundström et al[96]	820 (elderly Swedish GP)	↑
de Simone et al[97]	2758 (American Indian GP)	↑	Impaired	-	-	-	-
Burchfiel et al[98]	1572 (United States Black GP)	↑	-	-	-	-	-
de las Fuentes et al[99]	607 (United States GP)	↑	Impaired	-	-	-	-
Hwang et al[100]	1599 (South Korean GP)	↑	Impaired	-	-	-	-
Kim et al[101]	1886 (South Korean GP)		Impaired	=	-	-	↑
Ingelsson et al[102]	1945 (United States GP)	↑	-	↑	↑	-	-
Ferrara et al[103]	340 (Italian hypertensives)	↑		=
Aksoy et al[105]	90 (Turkish subjects)	↑	Impaired	-	-	-	-
Mulè et al[88]	93 (Italian hypertensives)	-	-	-	-	-	↑
Schillaci et al[119]	169 (Italian hypertensives)	-	-	-	↑	-	↑
Scuteri et al[120]	20750 (9 cohorts from Europe and United States)	-	-		-	-	↑
Scuteri et al[121]	6148 (Italian GP aged 14-102 years)	-	-	↑	-	-	↑
Scuteri et al[122]	471 (United States GP)	-	-	↑	-	-	↑
Zanchetti et al[28]	2034 (European hypertensives)	-	-	↑	-	-	-
Kawamoto et al[124]	760 (Japanese patients)	-	-	↑	-	-	-
Irace et al[125]	1853 (Italian GP)			=
Chen et al[110]	6217 (United States GP)	-	-	-	↑	↑	-
Chen et al[109]	15160 (Chinese GP)	-	-	-	↑	↑	-
Navarro et al[111]	8425 (Spanish hypertensives)	-	-	-	-	↑	-
Johns et al[112]	574 (United States non-diabetic GP)	-	-	-	-	↑	-

¹Only in women. LVM: Left ventricular mass; IMT: Intima-media thickness; CKD: Chronic kidney disease; =: No difference; ↑: Increased; -: Not evaluated; LV: Left ventricular; GP: General population.

Table 3 Therapeutic approaches in patients with metabolic syndrome

Metabolic syndrome component	Goal of therapy	Drugs	Diet	Physical exercise
Arterial hypertension	BP < 140/90 mmHg	ACEI or ARBs and/ or Ca-antagonists and/ or alpha-blockers1 Limit diuretics and beta-blockers	Salt restriction and hypocaloric	Regular exercise
Hyperglycemia	HbA1c < 7%-6.5%	Metformin GLP-1-Agonists DPP-4-inhibitors	Hypocaloric	Regular exercise
Obesity	Weight loss 7%-10%	Orlistat Bariatric Surgery	Hypocaloric	Regular exercise
Dyslipidemia	LDL < 100-70 mg/dL TG < 150 mg/dL HDL: Men > 40/ Women > 50 mg/dL	Statins ± ezetimibe. PUFA-n-3, Fibrates	Hypocaloric	Regular exercise

¹Not first choice. BP: Blood pressure; ACEI: Angiotensin converting enzyme inhibithors; ARBs: Angiotensin II receptor blockers; GLP-1: Glucagon-like peptide-1; DPP-4: Dipeptidyl peptidase-4; LDL: Low-density lipoprotein; TG: Triglycerides; HDL: High-density lipoprotein; PUFA-n-3: Omega-3-Polyunsaturated.